SEARCH

Search Details

Takada Ayato

International Institute for Zoonosis Control Division of Global EpidemiologyProfessor
One Health Research CenterProfessor

Researcher basic information

■ Degree
  • (BLANK), Hokkaido University
■ URL
researchmap URLホームページURL■ Various IDs
J-Global ID■ Research Keywords and Fields
Research Keyword
  • diagnostics
  • anti-virals
  • 自然宿主
  • 宿主域
  • ワクチン
  • 疫学
  • レセプター
  • 侵入機構
  • 病原性
  • ウイルス
  • Pathogenesis
  • Vaccine
  • Immunity
  • Virus
Research Field
  • Life Science, Virology
  • Life Science, Veterinary medical science
■ Educational Organization

Career

■ Career
Career
  • Jun. 2009 - Present
    Rocky Mountain Laboratories, Hamilton, Montana, USA., Special Volunteer
  • Oct. 2007 - Present
    School of Veterinary Medicine, University of Zambia, Visiting Professor
  • 2006 - Present
    Kobe University, 客員教授
  • May 2005 - Present
    Hokkaido University, Research Center for Zoonosis Control, Professor
  • Dec. 2000 - 2009
    Canadian Science Centre for Human and Animal Health, Visiting Scientist
  • 2000 - 2004
    The University of Tokyo, The Institute of Medical Science
  • 1997 - 2000
    Hokkaido University, Graduate School of Veterinary Medicine
  • 1997 - 2000
    Hokkaido University,
  • Assistant Professor
  • Graduate School of Veterinary Medicine,
Educational Background
  • 1996, Hokkaido University, 獣医学研究科, 予防治療学, Japan
  • 1996, Hokkaido University, Graduate School, Division of Veterinary Medicine
  • 1993, Hokkaido University, School of Veterinary Medicine, 獣医学, Japan
  • 1993, Hokkaido University, Faculty of Veterinary Medicine
Committee Memberships
  • Jan. 2016 - Present
    日本ウイルス学会, 理事, Society
  • 2014 - Present
    日本獣医学会獣医学奨励賞選考委員会, 委員, Society
  • 2012 - Present
    The International Committee on Taxonomy of Viruses (ICTV), Filoviridae Study Group, Others
  • 2010 - Present
    日本ウイルス学会, バイオセーフティー委員, Society
  • 2009 - Present
    日本ウイルス学会北海道支部, 幹事, Society
  • 2007 - Present
    日本ウイルス学会, ウイルス学将来構想検討委員, Society
  • Sep. 2017 - Sep. 2019
    日本獣医学会, 評議委員, Society
  • May 2016 - Mar. 2017
    文部科学省, 感染症研究の今後の在り方に関する検討委員会委員, Government
  • Mar. 2011 - Mar. 2014
    日本ウイルス学会, 理事, Society
Position History
  • 人獣共通感染症国際共同研究所長, 2023年4月1日 - 2025年3月31日
  • 大学院国際感染症学院副学院長, 2017年4月1日 - 2019年3月31日
  • 大学院国際感染症学院副学院長, 2019年4月1日 - 2021年3月31日

Research activity information

■ Awards
  • Feb. 2022, Hokkaido University, 教育研究総長表彰
    髙田 礼人
  • Jan. 2017, 北海道大学, 北海道大学研究総長賞 奨励賞
    高田 礼人
  • Feb. 2016, Hokkaido University, Hokkaido University President's Award for Outstanding Research
    TAKADA Ayato
  • Feb. 2015, Hokkaido University, Hokkaido University President's Award for Outstanding Research
    TAKADA Ayato
  • 2005, 日本ウイルス学会 杉浦奨励賞
    Japan
■ Papers
  • Characterization of H5N1 high pathogenicity avian influenza virus belonging to clade 2.3.4.4b isolated from Ezo red fox in Japan in a mouse model.
    Shintaro Shichinohe; Takahiro Hiono; Yasushi Itoh; Kosuke Takada; Yurie Kida; Pei Wang; Daisuke Motooka; Norikazu Isoda; Ayato Takada; Yoshihiro Sakoda; Tokiko Watanabe
    Microbiology spectrum, 14, 1, e0109725, 06 Jan. 2026, [International Magazine]
    English, Scientific journal, H5N1 high pathogenicity avian influenza virus (HPAIV) has spread in wild birds and poultry worldwide. H5N1 HPAIV belonging to the currently predominant clade 2.3.4.4b has infected not only birds but also mammals (wild and domestic animals), with several human infections also being reported, raising concerns for public health. In 2022, a clade 2.3.4.4b H5N1 HPAIV strain, A/Ezo red fox/Hokkaido/1/2022 (H5N1; Fox/Hok/1/22), was isolated from an Ezo red fox (Vulpes vulpes schrencki) in Hokkaido, Japan; this was the first reported case of clade 2.3.4.4b H5N1 HPAIV isolation from a mammalian species in Japan. Several amino acid substitutions in the PB2 protein play an important role in the adaptation of avian influenza viruses to mammals, but Fox/Hok/1/22 PB2 does not have any of these well-known mammalian-adapting PB2 substitutions. Here, we investigated the biological properties of Fox/Hok/1/22 in a mouse model and found that this virus was highly virulent in mice and replicated well in multiple organs, including the lungs and brain. We then examined whether viruses isolated from these organs acquired known mammalian-adapting PB2 amino acid substitutions, such as PB2 E627K. Deep sequencing analysis of viral RNA from mouse brain and lungs revealed that virus with PB2-627E was predominant in three of four mice, whereas the PB2-627K substitution was predominant in one mouse. These results indicate that Fox/Hok/1/22 is highly virulent in mice despite lacking known PB2 substitutions involved in mammalian adaptation.IMPORTANCEThe H5N1 avian influenza virus has caused severe disease in birds worldwide and is now spreading to mammals, including humans. In 2022, this virus was detected for the first time in an Ezo red fox in Japan. To understand its potential impact on mammals, we studied this virus in mice and found that it caused severe illness, spreading to multiple organs, including the lungs and brain. Surprisingly, despite lacking genetic mutations typically associated with mammalian adaptation, the virus was highly virulent in mice. This finding suggests that the H5N1 virus may pose a greater threat to mammals, including humans, than previously thought. Given their continued spread among wild and domestic animals, our findings underscore the urgent need to monitor how recent H5N1 viruses behave in mammals.
  • Discovery of potent cross-neutralizing antibodies against Marburg and Ravn viruses with therapeutic potential.
    Takeshi Saito; Hiroko Miyamoto; Manabu Igarashi; Asuka Nanbo; Risa Hayashi; Ruchi Paroha; Gavriella Siman-Tov; Kirsten Littlefield; Akina Mori-Kajihara; Christine Click; Wakako Furuyama; Slobodan Paessler; Junki Maruyama; Ayato Takada
    Npj viruses, 3, 1, 84, 84, 27 Dec. 2025, [International Magazine]
    English, Scientific journal, Marburg virus (MARV) and Ravn virus (RAVV) are highly pathogenic filoviruses that cause Marburg virus disease (MVD), for which no approved treatment currently exists. In this study, we describe a panel of 10 novel mouse-derived monoclonal antibodies (mAbs), all exhibiting neutralizing activity against MARV. Notably, five of these mAbs also cross-neutralize RAVV. Based on amino acid sequences, neutralization profiles, and escape mutations in the MARV glycoprotein (GP), the mAbs were classified into three groups. mAbs targeting the receptor-binding domain (RBD) and mucin-like domain exhibited MARV-specific neutralization, whereas those targeting epitopes spanning the RBD and internal fusion loop exhibited cross-neutralization. Post-exposure administration of cross-neutralizing mAbs (AGP-R7, AGP-R12) provided significant protection in MARV and RAVV infection mouse models. These findings identify a conserved neutralizing epitope with therapeutic potential and highlight AGP-R7 and AGP-R12 as promising candidates for MVD treatment. This study offers new insights into cross-reactive antibody strategies against multiple filoviruses.
  • Modulation of translational elongation by montanine alkaloids preferentially inhibits RNA viruses
    Ryuichi Sakai; Kyohei Sato; Atsushi Tsugita; Lakkana Thaveepornkul; Ayato Takada; Hiroko Miyamoto; Rumi Kurokawa; Minoru Yoshida; Takeshi Yokoyama; Antonio Evidente; Yuichiro Tsuge; Hiromi Watari; Tomonosuke Sumiya; Ken Matsumoto; Sarin Chimnaronk; Yoshikazu Tanaka
    openRxiv, 20 Dec. 2025
    Abstract

    Montanine, an Amaryllidaceae alkaloid, has demonstrated superior antiviral activity against dengue virus (DENV), SARS-CoV-2, vesicular stomatitis Indiana virus (VSV-G), and vesicular stomatitis virus pseudotyped with Ebola virus glycoprotein (VSV-ZGP), outperforming other antiviral alkaloids tested, including lycorine, narciclasine, tetracetylnarciclasine, and pancracine. We further showed that montanine inhibits translation in mammalian cells, as evidenced by a puromycin incorporation assay. Cryo-EM analysis revealed that montanine binds to the peptidyl transferase center of the human ribosome. A chemical genomics survey indicated that the knockdown of the GCN1 complex, which senses ribosome collisions and triggers the translation quality control process, increased the cytotoxicity of montanine while reducing viral infectivity. Together, these results suggest that the antiviral activity of montanine is closely linked to its impact on translational elongation and GCN1-related stress responses, underscoring the potential of translation control as a targeted mode for RNA virus therapeutics.

    Significance Statement

    Montanine, an alkaloid from the Amaryllidaceae family known for its diverse bioactivities, was identified as a potent antiviral compound from a library of natural plant- and fungus-derived substances. Through a combination of biochemical assays and cryo-EM analysis, we discovered that montanine binds to the peptidyl transfer center of the human ribosome, effectively inhibiting protein synthesis. Based on these findings and a chemical genomics approach, we hypothesize that the translational control of montanine triggers a cellular response that impedes viral replication. We propose that molecules capable of modulating translation efficacy could serve as unique lead compounds in the development of broad-spectrum antiviral agents.
  • Oita virus rediscovered after 50 years: isolation of genetically conserved strains from bats in Southern Japan
    Saiko Sawai; Kittiya Intaruck; Sho Sata; Mana Esaki; Kimitake Funakoshi; Shin Murakami; Keita Matsuno; Ryo Nakao; Kazunori Kimitsuki; Takaaki Yahiro; Akira Nishizono; Naganori Nao; Yasuko Orba; Ayato Takada; Masahiro Kajihara; Makoto Ozawa; Kosuke Okuya
    Microbiology Spectrum, American Society for Microbiology, 11 Nov. 2025
    Scientific journal, ABSTRACT

    Bats are natural reservoirs of numerous viruses, including members of the Rhabdoviridae family. Oita virus (OITV), classified within the genus Ledantevirus , was first isolated from the blood of a Japanese horseshoe bat ( Rhinolophus cornutus ) in the Oita Prefecture, Japan, in 1972. However, since then, no other OITV isolates have been reported. In this study, we isolated two OITV strains—OITV 321/2022 and OITV 326/2022—from oral swab samples of R. cornutus collected in the Katano Cave, Kagoshima Prefecture, Japan. Genetic analysis revealed >98% nucleotide identity with the previous isolate, OITV 296/1972. Phylogenetic analysis confirmed their classification within the Ledantevirus subgroup C. We assessed viral growth kinetics using 17 cell lines from diverse animal species, including bats, rodents, humans, and arthropods. OITV 321/2022 showed efficient replication in primate-derived, bat-derived, and human-derived cells, but not in tick or mosquito cell lines. Experimental infection of BALB/c mice demonstrated that OITV 321/2022 induced no overt clinical signs via either the intracerebral or intranasal routes. However, systemic infection and viral replication in the brain and lungs were observed by intracerebral inoculation. Intranasal inoculation with OITV 321/2022 and OITV 296/1972 resulted in transient pulmonary infection without systemic dissemination. This study provides evidence of OITV circulation in wild bat populations over 50 years, highlighting the need for continued surveillance of bat-associated rhabdoviruses in Japan.

    IMPORTANCE

    Bats are known reservoirs of zoonotic viruses, and their proximity to humans raises concerns regarding zoonotic risks. We report the first isolation of the Oita virus (OITV), a bat-associated ledantevirus, that has circulated for over 50 years. Unlike a previous blood-derived isolate, our isolates were obtained from oral swabs, suggesting their potential for respiratory transmission. OITV could infect a wide range of mammalian cells, including human-derived cells, and induce systemic infection in mice without clinical symptoms. These findings indicate that OITV possesses a broad host tropism and may circulate among microbats through the respiratory tract. Although the pathogenicity of the newly isolated strain appears to be attenuated compared with that of a historical brain-passaged strain, its ability to replicate in human cells underscores its potential zoonotic relevance, necessitating active surveillance and functional characterization of bat-derived rhabdoviruses to better assess emerging infectious disease threats.
  • Comparison of the biological properties of bat-derived filovirus envelope glycoproteins.
    Francois Edidi-Atani; Yannick Munyeku Bazitama; Hiroko Miyamoto; Akina Mori-Kajihara; Hayato Sugiura; Manabu Igarashi; Jean Jacques Muyembe-Tamfum; Steve Ahuka-Mundeke; Ayato Takada
    Journal of virology, e0101825, 25 Sep. 2025, [International Magazine]
    English, Scientific journal, Although some filoviruses, such as Ebola virus (EBOV) and Marburg virus (MARV), are highly pathogenic in humans, novel filoviruses, including Lloviu virus (LLOV), Bombali virus (BOMV), Mengla virus (MLAV), and Dehong virus (DEHV), whose biological properties are poorly understood, have been found in bats. In this study, we characterized the envelope glycoproteins (GPs) of these bat-derived filoviruses (BatFiloVs). We first confirmed that virus-like particles consisting of their GPs, nucleoproteins, and matrix proteins were filamentous. Interestingly, although BatFiloVs were serologically distinct, some previously established monoclonal antibodies (MAbs) (e.g., 6D6) successfully neutralized vesicular stomatitis Indiana viruses pseudotyped with LLOV, BOMV, or DEHV GPs. The pseudotyped viruses bearing BatFiloV GPs utilized human TIM-1 and C-type lectins for entry into cells, although the efficiency tended to be lower than for EBOV and/or MARV GP-pseudotyped viruses. These viruses broadly infected cultured cells derived from various animal species, including humans and bats. However, viruses pseudotyped with DEHV and MARV GPs failed to infect the Yaeyama flying fox cell line, whereas the other pseudotyped viruses infected this cell line. Interestingly, the virus bearing BOMV GP showed the greatest ability to infect cell lines derived from Angolan free-tailed bats, the only known host species of BOMV. We identified unique amino acid residues at the interface between GP and its receptor (i.e., Niemann-Pick C1), which might explain these differences. Our results suggest that the biological properties of filovirus GPs are generally consistent with their phylogenetic relationship and that BatFiloVs may have differential pathogenicity and host range restriction.IMPORTANCEFiloviruses, such as EBOV and MARV, are known to cause severe hemorrhagic fever in humans and nonhuman primates. With the recent advancements in next-generation sequencing, novel filoviruses have been detected in bats. However, their pathogenicity and host tropism remain largely unknown. Here, we focus on the filovirus spike protein GP, which plays a crucial role in the viral lifecycle, and discuss the biological properties of BatFiloVs. We studied the primary structures of GPs, virus particle morphology, antigenic differences of GPs, neutralizing capacities of anti-EBOV and -MARV GP MAbs, usage of some attachment factors during the entry into cells, and GP-mediated cellular tropism. The present study provides fundamental information for understanding the BatFiloV ecology, host ranges, and potential risks as zoonotic pathogens for humans. This knowledge will guide public health interventions to prevent virus spillovers and the development of surveillance strategies and specific countermeasures.
  • Annual (2024) taxonomic update of RNA-directed RNA polymerase-encoding negative-sense RNA viruses (realm Riboviria: kingdom Orthornavirae: phylum Negarnaviricota).
    Jens H Kuhn; Scott Adkins; Sergey V Alkhovsky Альховский Сергей Владимирович; Wenxia An 安雯霞; Tatjana Avšič-Županc; María A Ayllón; Katarina Bačnik; Justin Bahl; Anne Balkema-Buschmann; Matthew J Ballinger; Martin Beer; Nicolas Bejerman; Éric Bergeron; Nadine Biedenkopf; Carol D Blair; Kim R Blasdell; Steven B Bradfute; Thomas Briese; Katherine Brown; Paul A Brown; Ursula J Buchholz; Michael J Buchmeier; Alexander Bukreyev; Felicity Burt; Charles H Calisher; Sten Calvelage; Mengji Cao 曹孟籍; Inmaculada Casas; Camila Chabi-Jesus; Kartik Chandran; Rémi N Charrel; Anya Crane; Laura N Cuypers; Elena Dal Bó; Juan Carlos de la Torre; William M de Souza; Rik L de Swart; Humberto J Debat; Nolwenn M Dheilly; Nicholas Di Paola; Francesco Di Serio; Ralf G Dietzgen; Michele Digiaro; J Felix Drexler; W Paul Duprex; Ralf Dürrwald; Andrew J Easton; Toufic Elbeaino; Koray Ergünay; Mirette I Y Eshak; Guozhong Feng 冯国忠; Andrew E Firth; Anthony R Fooks; Pierre B H Formenty; Juliana Freitas-Astúa; Conrad M Freuling; Tuija Gadd; Selma Gago-Zachert; María Laura García; Adolfo García-Sastre; Aura R Garrison; Tony L Goldberg; Jean-Paul J Gonzalez; Joëlle Goüy de Bellocq; Anthony Griffiths; Martin H Groschup; Sophie Gryseels; Ion Gutiérrez-Aguirre; Stephan Günther; John Hammond; Jussi Hepojoki; Masayuki Horie 堀江真行; Adam J Hume; Timothy H Hyndman; Dirk Höper; Dàohóng Jiāng 姜道宏; Sandra Junglen; Boris Klempa; Jonas Klingström; Hideki Kondō 近藤秀樹; Eugene V Koonin; Mart Krupovic; Kenji Kubota 久保田健嗣; Gael Kurath; Denis Kutnjak; Lies Laenen; Amy J Lambert; Benhur Lee; Chengyu Li 李呈宇; Jiànróng Lǐ 李建荣; Jun-Min Li 李俊敏; Igor S Lukashevich; Piet Maes; Marco Marklewitz; Sergio H Marshall; Shin-Yi L Marzano; John W McCauley; Nataša Mehle; Ali Mirazimi; Toshiyuki Morikawa 守川俊幸; Elke Mühlberger; Thomas Müller; Rayapati Naidu; Tomohide Natsuaki 夏秋知英; Beatriz Navarro; José A Navarro; Yutaro Neriya 煉谷裕太朗; Sergey V Netesov Нетёсов Сергей Викторович; Vittorio M Nicoloso; Gabriele Neumann; Tiina Nokireki; Norbert Nowotny; Márcio R T Nunes; Francisco M Ochoa-Corona; Gustavo Palacios; Vicente Pallás; Anna Papa Άννα Παπά; Sofia Paraskevopoulou Σοφία Παρασκευοπούλου; Colin R Parrish; Alex Pauvolid-Corrêa; Anja Pecman; Daniel R Pérez; Florian Pfaff; Richard K Plemper; Thomas S Postler; Sheli R Radoshitzky; Pedro L Ramos-González; Maja Ravnikar; Renato O Resende; Gábor Reuter; Carina A Reyes; Mark Paul Selda Rivarez; Víctor Romanowski; Dennis Rubbenstroth; Luisa Rubino; Jonathan A Runstadler; Ana Ruiz-Padilla; Sead Sabanadzovic; Maria S Salvato; Takahide Sasaya 笹谷孝英 I; Connie S Schmaljohn; Heike Schmidt-Posthaus; Martin Schwemmle; Gabrijel Seljak; Torsten Seuberlich; Mang Shi 施莽; Yoshifumi Shimomoto 下元祥史; Peter Simmonds; Manuela Sironi; Donald B Smith; Sophie Smither; Jin-Won Song 송진원; Kirsten M Spann; Jessica R Spengler; Mark D Stenglein; Ayato Takada 高田礼人; Chika Takemura; Niina Tammiranta; Robert B Tesh; Natalie J Thornburg; Nicole D Tischler; Yasuhiro Tomitaka 冨髙保弘; Keizō Tomonaga 朝長啓造; Noël Tordo; Massimo Turina; Ioannis E Tzanetakis Ιωάννης Ε Τζανετάκης; Anna Maria Vaira; Bernadette van den Hoogen; Bert Vanmechelen; Nikos Vasilakis Νίκος Βασιλάκης; Martin Verbeek; Susanne von Bargen; Ana Vučurović; Jiro Wada 和田治郎; Victoria Wahl; Peter J Walker; Fei Wang 王飞; Anna E Whitfield; John V Williams; Yuri I Wolf; Hironobu Yanagisawa 栁澤広宣; Caixia Yang 杨彩霞; Gongyin Ye 叶恭银; Mei Chun Yu 于美春; F Murilo Zerbini; Song Zhang; Arnfinn Lodden Økland; Holly R Hughes
    The Journal of general virology, 106, 6, Jun. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, In April 2024, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was expanded by 1 new order, 1 new family, 6 new subfamilies, 34 new genera and 270 new species. One class, two orders and six species were renamed. Seven families and 12 genera were moved; ten species were renamed and moved; and nine species were abolished. This article presents the updated taxonomy of Negarnaviricota as currently accepted by the ICTV, providing an essential annual update on the classification of members of this phylum that deepen understandings of their evolution, and supports critical public health measures for virus identification and tracking.
  • Immunochromatographic Lateral Flow Assays to Detect Filovirus Nucleoproteins.
    Shino Muramatsu; Daisuke Kato; Ayato Takada
    Methods in molecular biology (Clifton, N.J.), 2877, 421, 430, 2025, [Peer-reviewed], [Invited], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, The recent large outbreaks of Ebola virus disease in West Africa and the Democratic Republic of the Congo have highlighted the need for rapid diagnostic tests to control this disease. In this chapter, the development of immunochromatographic lateral flow assays to detect filovirus nucleoproteins is described as an example of designing rapid diagnostic tests.
  • Evidence of multiple bacterial, viral, and parasitic infectious disease agents in Mastomys natalensis rodents in riverine areas in selected parts of Zambia.
    Samuel Munalula Munjita; Annie Kalonda; Benjamin Mubemba; Manu Vanaerschot; Cristina Tato; Lusajo Mwakibete; John Tembo; Simbarashe Chitanga; Katendi Changula; Masahiro Kajihara; Walter Muleya; Hirofumi Sawa; Ayato Takada; Matthew Bates; Sody Munsaka; Edgar Simulundu
    Infection ecology & epidemiology, 15, 1, 2441537, 2441537, 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Infectious disease agents pose significant threats to humans, wildlife, and livestock, with rodents carrying a third of these agents, many linked to human diseases. However, the range of pathogens in rodents and the hotspots for disease remain poorly understood. AIM: This study evaluated the prevalence of viral, bacterial, and parasitic pathogens in Mastomys natalensis rodents in riverine and non-riverine areas in selected districts in Zambia. METHODS: The study applied metagenomic next generation sequencing (mNGS). Tissues analysed included semen, foetal tissues, and blood-rich organs (liver, spleen, kidneys, and lungs). A multivariate logistic regression model explored the relationship between pathogen presence and host or ecological factors. RESULTS: A total of 182 rodents were captured, and 14 pathogens were detected in 10.4% of the samples (19/182). Detected organisms included zoonoses (Klebsiella michiganensis, Klebsiella pneumoniae, Salmonella enterica, and Bartonella elizabethae); Emerging zoonoses (Elizabethkingia miricola, Klebsiella variicola, Bartonella tribocorum, and Cardiovirus B); among others (Eimeria papillata etc). Riverine areas showed higher odds of pathogen presence (OR = 8.45; p < 0.001; 95% CI: 3.07-23.26). CONCLUSION: These results suggest that M. natalensis harbours multiple infectious agents with zoonotic potential, and riverine regions may be key hotspots for rodent-borne pathogens in Zambia.
  • Evidence of human exposure and associated risk factors to Rift Valley fever in selected districts of Central and Western Zambia.
    Chilufya C Kasongamulilo; Michelo Syakalima; Ngondo Saasa; Henson Kainga; Girja S Pandey; Andrew N Mukubesa; Innocent Mwape; Masahiro Kajihara; Ayato Takada; Martin Simuunza
    PloS one, 20, 1, e0309288, 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Rift Valley fever (RVF) is an important viral zoonotic disease that not only affects ruminants but causes serious morbidity and mortality in humans. In humans, its symptoms range from mild flu-like signs to a severe form such as retinal damage, meningoencephalitis to haemorrhagic fever. In this study, 202 human serum samples were collected from central and western parts of Zambia and tested for RVF-specific antibodies using a commercially available ELISA kit. A pre-tested semi-structured questionnaire was used to collect data for determining hypothesised risk factors for exposure to RVF. The participants enrolled in this study, were only those who are at high risk of RVF infection and were in close contact with animals and animal products. The study revealed an overall seropositivity of 9.90%, occupationally distributed as 16.67% among slaughter house workers, 14.41% among livestock farmers, and 0% among the others (i.e., students, butchery, and farm workers). The prevalence was highest (19.23%) in Sesheke district found in the western part of Zambia, while Chisamba district in central Zambia had the lowest prevalence (1.41). Movement of animals in search of greener pastures was identified as a risk factor to being RVF-seropositive. This suggests that there was silent circulation of the virus in the interepidemic period in the study areas. Therefore, this study recommends that public education of livestock farmers, public health workers, slaughterhouse workers, communities, livestock and veterinary staff needs to be enhanced to increase awareness and preparedness for RVF outbreak in Zambia.
  • First identification and whole genome characterization of rotavirus C in pigs in Zambia.
    Hayato Harima; Yongjin Qiu; Michihito Sasaki; Joseph Ndebe; Kapila Penjaninge; Edgar Simulundu; Masahiro Kajihara; Aiko Ohnuma; Keita Matsuno; Naganori Nao; Yasuko Orba; Ayato Takada; Kanako Ishihara; William W Hall; Bernard M Hang'ombe; Hirofumi Sawa
    Virology, 603, 110385, 110385, 31 Dec. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Rotavirus C (RVC) causes acute gastroenteritis in neonatal piglets. Despite the clinical importance of RVC infection, the distribution and prevalence in pig populations in most African countries remains unknown. In this study, we identified RVC in Zambian pigs by metagenomic analysis. The full genome sequence of the RVC revealed two different VP4 sequences, implying that two different RVC strains (ZP18-77-c1 and ZP18-77-c2) were present in the same sample. Genetic analyses demonstrated that all segments of ZP18-77-c1 and ZP18-77-c2 showed high nucleotide sequence identities (87.7-94.5%) to known porcine RVC strains, and ZP18-77-c1 and ZP18-77-c2 strains were assigned to genotype constellations, G1-P[4]/P[14]-I13-R5-C5-M1-A7-N9-T10-E5-H1. We further screened RVC genomes among pig feces collected in Zambia (n = 147) by RT-qPCR, and 78 samples (53.1%) were positive. This study demonstrated the first full genome sequence of African RVC strains with a relatively high prevalence of RVC infection in the pig populations in Zambia.
  • Lack of Lloviu Virus Disease Development in Ferret Model.
    Paige Fletcher; Kyle L O'Donnell; Joseph F Rhoderick; Corey W Henderson; Atsushi Okumura; Trenton Bushmaker; Ayato Takada; Chad S Clancy; Gábor Kemenesi; Andrea Marzi
    Emerging infectious diseases, 30, 12, 2639, 2642, Dec. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The first isolate of the emerging filovirus Lloviu virus (LLOV) was obtained in 2022. No animal disease models have been established. We assessed the pathogenic potential of LLOV in ferrets after intranasal, intramuscular, or aerosol exposure. The lack of disease development shows ferrets are not a disease model for LLOV.
  • Development of a seroepidemiological tool for bat-borne and shrew-borne hantaviruses and its application using samples from Zambia
    Rakiiya Sikatarii Sarii; Masahiro Kajihara; Zuoxing Wei; Sithumini M. W. Lokpathirage; Devinda S. Muthusinghe; Akina Mori-Kajihara; Katendi Changula; Yongjin Qiu; Joseph Ndebe; Bernard M. Hang’ombe; Fuka Kikuchi; Ai Hayashi; Motoi Suzuki; Hajime Kamiya; Satoru Arai; Ayato Takada; Kumiko Yoshimatsu
    PLOS Neglected Tropical Diseases, 18, 11, e0012669, e0012669, Public Library of Science (PLoS), 21 Nov. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Background

    Rodent-borne orthohantaviruses are the causative agents of hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Apart from the classic rodent-borne hantaviruses, numerous species of hantaviruses have been identified in shrews and bats; however, their antigenicity and pathogenicity are unknown. This study focused on developing a serological method to detect antibodies against bat- and shrew-borne hantaviruses.

    Methodology/Principal findings

    Five bat-borne (Brno, Dakrong, Quezon, Robina, and Xuan Song) and 6 shrew-borne (Asama, Altai, Cao Bang, Nova, Seewis, and Thottapalayam) viruses were selected based on the phylogenetic differences in their N proteins. The recombinant N (rN) proteins of these viruses were expressed as antigens in Vero E6 and 293T cell lines using the pCAGGS/MCS vector. Antisera against the Nus-tagged rN fusion proteins of these viruses (mouse anti-Brno, Dakrong, Quezon, Robina, Xuan Song, Asama, Cao Bang, and Nova, while rabbit anti-Altai, Seewis and Thottapalayam) were also generated. Antigenic cross-reactivity was examined in antisera and rN-expressing Vero E6 cells. The rN proteins of almost all the tested viruses, except for the Quezon and Robina viruses, showed independent antigenicity. For serological screening of bat samples, 5 rNs of the bat-borne viruses were expressed together in a single transfection protocol. Similarly, 6 rNs of shrew-borne viruses were expressed. Reactivities of the mixed antigen system were also examined across the singly transfected Vero cell lines to ensure that all antigens were expressed. Using these antigens, bat serum samples collected from Zambia were screened using the indirect immunofluorescence antibody test (IFAT). Selected positive samples were individually tested for the respective antigens by IFAT and western blot assays using rN-expressing 293T cell lysates. Of the 1,764 bat serum samples tested, 11.4% and 17.4% were positive for bat and shrew mixed antigens, respectively. These samples showed positive reactions to the Brno, Dakrong, Quezon, Xuan Son, Robina, Asama, Altai, Cao Bang, or Thottapalayam virus antigens.

    Conclusions/Significance

    These observations suggest that the mixed-antigen screening system is useful for serological screening For Orthohantavirus infections and that bats in Zambia are likely exposed to not only bat-borne hantaviruses but also to shrew-borne hantaviruses.
  • A first report of rotavirus B from Zambian pigs leading to the discovery of a novel VP4 genotype P[9].
    Hayato Harima; Yongjin Qiu; Michihito Sasaki; Joseph Ndebe; Kapila Penjaninge; Edgar Simulundu; Masahiro Kajihara; Aiko Ohnuma; Keita Matsuno; Naganori Nao; Yasuko Orba; Ayato Takada; Kanako Ishihara; William W Hall; Bernard M Hang'ombe; Hirofumi Sawa
    Virology journal, 21, 1, 263, 263, 24 Oct. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Rotavirus B (RVB) causes diarrhea in humans and pigs. Although various RVB strains were identified in humans and various animals globally, little is known about the epidemiology RVB infection in Africa. In this study, we attempted to examine the prevalence of RVB infection in pig populations in Zambia. METHODS: Metagenomic analyses were conducted on pig feces collected in Zambia to detect double stranded RNA viruses, including RVB. To clarify the prevalence of RVB infection in pig populations in Zambia, 147 fecal samples were screened for the RVB detection by RT-qPCR. Full genome sequence of a detected RVB was determined by Sanger sequencing and genetically analyzed. RESULTS: The metagenomic analyses revealed that RVB sequence reads and contigs of RVB were detected from one fecal sample collected from pigs in Zambia. RT-qPCR screening detected RVB genomes in 36.7% (54/147) of fecal samples. Among 54 positive samples, 13 were positive in non-diarrheal samples (n = 48, 27.1%) and 41 in diarrheal samples (n = 99, 41.4%). Genetic analyses demonstrated that all the segments of ZP18-18, except for VP4, had high nucleotide sequence identities (80.6-92.6%) with all other known RVB strains detected in pigs. In contrast, the VP4 sequence of ZP18-18 was highly divergent from other RVB strains (< 64.6% identities) and formed a distinct lineage in the phylogenetic tree. Notably, the VP8 subunit of the VP4 showed remarkably low amino acid identities (33.3%) to those of known RVB strains, indicating that the VP8 subunit of ZP18-18 was unique among RVB strains. According to the whole genome classification for RVB, ZP18-18 was assigned to a genotype constellation, G18-P[9]-I12-R4-C4-M4-A8-N10-T5-E4-H7 with the newly established VP4 genotype P[9]. CONCLUSIONS: This current study updates the geographical distribution and the genetic diversity of RVB. Given the lack of information regarding RVB in Africa, further RVB surveillance is required to assess the potential risk to humans and animals.
  • Stability of Bas-Congo virus neutralising antibodies in serum samples during long-term storage-Authors' reply.
    Yannick Munyeku-Bazitama; Patient Okitale-Talunda; Takanari Hattori; Takeshi Saito; Boniface Pongombo Lombe; Hiroko Miyamoto; Akina Mori-Kajihara; Masahiro Kajihara; Agathe Bikupe Nkoy; Augustin Tshibwabwa Twabela; Justin Masumu; Steve Ahuka-Mundeke; Jean-Jacques Muyembe-Tamfum; Manabu Igarashi; Eun-Sil Park; Shigeru Morikawa; Sheila Makiala-Mandanda; Ayato Takada
    The Lancet. Microbe, 5, 10, 100917, 100917, Oct. 2024, [Invited], [Last author, Corresponding author], [International Magazine]
    English
  • Non-Ebola Filoviruses: Potential Threats to Global Health Security.
    Yannick Munyeku-Bazitama; Francois Edidi-Atani; Ayato Takada
    Viruses, 16, 8, 23 Jul. 2024, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Filoviruses are negative-sense single-stranded RNA viruses often associated with severe and highly lethal hemorrhagic fever in humans and nonhuman primates, with case fatality rates as high as 90%. Of the known filoviruses, Ebola virus (EBOV), the prototype of the genus Orthoebolavirus, has been a major public health concern as it frequently causes outbreaks and was associated with an unprecedented outbreak in several Western African countries in 2013-2016, affecting 28,610 people, 11,308 of whom died. Thereafter, filovirus research mostly focused on EBOV, paying less attention to other equally deadly orthoebolaviruses (Sudan, Bundibugyo, and Taï Forest viruses) and orthomarburgviruses (Marburg and Ravn viruses). Some of these filoviruses have emerged in nonendemic areas, as exemplified by four Marburg disease outbreaks recorded in Guinea, Ghana, Tanzania, and Equatorial Guinea between 2021 and 2023. Similarly, the Sudan virus has reemerged in Uganda 10 years after the last recorded outbreak. Moreover, several novel bat-derived filoviruses have been discovered in the last 15 years (Lloviu virus, Bombali virus, Měnglà virus, and Dehong virus), most of which are poorly characterized but may display a wide host range. These novel viruses have the potential to cause outbreaks in humans. Several gaps are yet to be addressed regarding known and emerging filoviruses. These gaps include the virus ecology and pathogenicity, mechanisms of zoonotic transmission, host range and susceptibility, and the development of specific medical countermeasures. In this review, we summarize the current knowledge on non-Ebola filoviruses (Bombali virus, Bundibugyo virus, Reston virus, Sudan virus, Tai Forest virus, Marburg virus, Ravn virus, Lloviu virus, Měnglà virus, and Dehong virus) and suggest some strategies to accelerate specific countermeasure development.
  • Characterization of human tibrovirus envelope glycoproteins
    Yannick Munyeku-Bazitama; Takeshi Saito; Takanari Hattori; Hiroko Miyamoto; Boniface Pongombo Lombe; Akina Mori-Kajihara; Masahiro Kajihara; Jean-Jacques Muyembe-Tamfum; Manabu Igarashi; Eun-sil Park; Shigeru Morikawa; Sheila Makiala-Mandanda; Ayato Takada
    Journal of Virology, 98, 7, e0049924, American Society for Microbiology, 02 Jul. 2024, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, ABSTRACT

    Tibroviruses are novel rhabdoviruses detected in humans, cattle, and arthropods. Four tibroviruses are known to infect humans: Bas-Congo virus (BASV), Ekpoma virus 1 (EKV-1), Ekpoma virus 2, and Mundri virus. However, since none of them has been isolated, their biological properties are largely unknown. We aimed to characterize the human tibrovirus glycoprotein (G), which likely plays a pivotal role in viral tropism and pathogenicity. Human tibrovirus Gs were found to share some primary structures and display 14 conserved cysteine residues, although their overall amino acid homology was low (29%–48%). Multiple potential glycosylation sites were found on the G molecules, and endoglycosidase H- and peptide-N-glycosidase F-sensitive glycosylation was confirmed. AlphaFold-predicted three-dimensional (3D) structures of human tibrovirus Gs were overall similar. Membrane fusion mediated by these tibrovirus Gs was induced by acidic pH. The low pH-induced conformational change that triggers fusion was reversible. Virus-like particles (VLPs) were produced by transient expression of Gs in cultured cells and used to produce mouse antisera. Using vesicular stomatitis Indiana virus pseudotyped with Gs, we found that the antisera to the respective tibrovirus VLPs showed limited cross-neutralizing activity. It was also found that human C-type lectins and T-cell immunoglobulin mucin 1 acted as attachment factors for G-mediated entry into cells. Interestingly, BASV-G showed the highest ability to utilize these molecules. The viruses infected a wide range of cell lines with preferential tropism for human-derived cells whereas the preference of EKV-1 was unique compared with the other human tibroviruses. These findings provide fundamental information to understand the biological properties of the human tibroviruses.

    IMPORTANCE

    Human tibroviruses are poorly characterized emerging rhabdoviruses associated with either asymptomatic infection or severe disease with a case fatality rate as high as 60% in humans. However, the extent and burden of human infection as well as factors behind differences in infection outcomes are largely unknown. In this study, we characterized human tibrovirus glycoproteins, which play a key role in virus-host interactions, mainly focusing on their structural and antigenic differences and cellular tropism. Our results provide critical information for understanding the biological properties of these novel viruses and for developing appropriate preparedness interventions such as diagnostic tools, vaccines, and effective therapies.
  • Detection of Human Adenovirus and Rotavirus in Wastewater in Lusaka, Zambia: Demonstrating the Utility of Environmental Surveillance for the Community
    Ngonda Saasa; Ethel M’kandawire; Joseph Ndebe; Mulenga Mwenda; Fred Chimpukutu; Andrew Nalishuwa Mukubesa; Fred Njobvu; Doreen Mainza Shempela; Jay Sikalima; Carol Chiyesu; Bruce Muvwanga; Sarah M. Nampokolwe; Clement Sulwe; Thokozile Khondiwa; Todd Jennings; Ameck Kamanga; Edgar Simulundu; Conceptor Mulube; Wizaso Mwasinga; Jalaimo Mumeka; John Simwanza; Patrick Sakubita; Otridah Kapona; Chilufya Susan Aneta Mulenga; Musole Chipoya; Kunda Musonda; Nathan Kapata; Nyambe Sinyange; Muzala Kapina; Joyce Siwila; Misheck Shawa; Masahiro Kajihara; Ayato Takada; Hirofumi Sawa; Simulyamana A. Choonga; Roma Chilengi; Earnest Muyunda; King S. Nalubamba; Bernard M. Hang’ombe
    Pathogens, 13, 6, 486, 486, MDPI AG, 07 Jun. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Enteric infections due to viral pathogens are a major public health concern. Detecting the risk areas requires a strong surveillance system for pathogenic viruses in sources such as wastewater. Towards building an environmental surveillance system in Zambia, we aimed to identify group A rotavirus (RVA) and human adenovirus (HAdV) in wastewater. Convenient sampling was conducted at four study sites every Tuesday for five consecutive weeks. The research team focused on three different methods of viral concentration to determine the suitability in terms of cost and applicability for a regular surveillance system: the bag-mediated filtration system (BMFS), polyethylene glycol-based (PEG) precipitation, and skimmed milk (SM) flocculation. We screened 20 wastewater samples for HAdV and RVA using quantitative polymerase chain reaction (qPCR) and conventional polymerase chain reaction (cPCR). Of the 20 samples tested using qPCR, 18/20 (90%) tested positive for HAdV and 14/20 (70%) tested positive for RVA. For the genetic sequencing, qPCR positives were subjected to cPCR, of which 12 positives were successfully amplified. The human adenovirus was identified with a nucleotide identity range of 98.48% to 99.53% compared with the reference genome from GenBank. The BMFS and SM flocculation were the most consistent viral concentration methods for HAdV and RVA, respectively. A statistical analysis of the positives showed that viral positivity differed by site (p < 0.001). SM and PEG may be the most appropriate options in resource-limited settings such as Zambia due to the lower costs associated with these concentration methods. The demonstration of HAdV and RVA detection in wastewater suggests the presence of the pathogens in the communities under study and the need to establish a routine wastewater surveillance system for the identification of pathogens.
  • Pathogenic differences of cynomolgus macaques after Taï Forest virus infection depend on the viral stock propagation.
    Paige Fletcher; Chad S Clancy; Kyle L O'Donnell; Brianna M Doratt; Delphine C Malherbe; Joseph F Rhoderick; Friederike Feldmann; Patrick W Hanley; Ayato Takada; Ilhem Messaoudi; Andrea Marzi
    PLoS pathogens, 20, 6, e1012290, Jun. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Taï Forest virus (TAFV) is a negative-sense RNA virus in the Filoviridae family. TAFV has caused only a single human infection, but several disease outbreaks in chimpanzees have been linked to this virus. Limited research has been done on this human-pathogenic virus. We sought to establish an animal model to assess TAFV disease progression and pathogenicity at our facility. We had access to two different viral stock preparations from different institutions, both originating from the single human case. Type I interferon receptor knockout mice were inoculated with TAFV stock 1 or stock 2 by the intraperitoneal route. Inoculation resulted in 100% survival with no disease regardless of viral stock preparation or infectious dose. Next, cynomolgus macaques were inoculated with TAFV stock 1 or stock 2. Inoculation with TAFV stock 1 resulted in 100% survival and robust TAFV glycoprotein-specific IgG responses including neutralizing antibodies. In contrast, macaques infected with TAFV stock 2 developed disease and were euthanized 8-11 days after infection exhibiting viremia, thrombocytopenia, and increased inflammatory mediators identified by transcriptional analysis. Histopathologic analysis of tissue samples collected at necropsy confirmed classic filovirus disease in numerous organs. Genomic differences in both stock preparations were mapped to several viral genes which may have contributed to disease severity. Taken together, we demonstrate that infection with the two TAFV stocks resulted in no disease in mice and opposing disease phenotypes in cynomolgus macaques, highlighting the impact of viral stock propagation on pathogenicity in animal models.
  • Molecular characterization of an avian rotavirus a strain detected from a large-billed crow (Corvus macrorhynchos) in Japan.
    Yuji Fujii; Tatsunori Masatani; Shoko Nishiyama; Tatsuki Takahashi; Misuzu Okajima; Fumiki Izumi; Yoshihiro Sakoda; Ayato Takada; Makoto Ozawa; Makoto Sugiyama; Naoto Ito
    Virology, 596, 110114, 110114, 18 May 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Avian rotaviruses A (RVAs) are occasionally transmitted to animals other than the original hosts across species barriers. Information on RVAs carried by various bird species is important for identifying the origin of such interspecies transmission. In this study, to facilitate an understanding of the ecology of RVAs from wild birds, we characterized all of the genes of an RVA strain, JC-105, that was detected in a fecal sample of a large-billed crow (Corvus macrorhynchos) in Japan. All of the genes of this strain except for the VP4 and VP7 genes, which were classified as novel genotypes (P[56] and G40, respectively), were closely related to those of the avian-like RVA strain detected from a raccoon, indicating the possibility that crows had been involved in the transmission of avian RVAs to raccoons. Our findings highlight the need for further viral investigations in wild birds and mammals to understand the mechanisms of avian-to-mammal RVA transmission.
  • Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities.
    Ryuichi Sakai; Ken Matsumura; Hajime Uchimasu; Kei Miyako; Tohru Taniguchi; V Raghavendra Rao Kovvuri; Anjana Delpe Acharige; Kenneth G Hull; Daniel Romo; Lakkana Thaveepornkul; Sarin Chimnaronk; Hiroko Miyamoto; Ayato Takada; Hiromi Watari; Masaki J Fujita; Jiro Sakaue
    The Journal of organic chemistry, 89, 9, 5977, 5987, 01 Apr. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Mellpaladines A-C (1-3) and dopargimine (4) are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (5), three additional mellpaladines D-F (6-8), and serotodopalgimine (9), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (10). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound 4 and its congeners dopargine (11), nordopargimine (15), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine (16) were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of 1-4 using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for in vivo behavioral toxicity. Interestingly, these alkaloids also emerged during a screen of our marine natural product library aimed at identifying antiviral activities against dengue virus, SARS-CoV-2, and vesicular stomatitis Indiana virus (VSV) pseudotyped with Ebola virus glycoprotein (VSV-ZGP).
  • Seroprevalence of Bas-Congo virus in Mangala, Democratic Republic of the Congo: a population-based cross-sectional study
    Yannick Munyeku-Bazitama; Patient Okitale-Talunda; Takanari Hattori; Takeshi Saito; Boniface Pongombo Lombe; Hiroko Miyamoto; Akina Mori-Kajihara; Masahiro Kajihara; Agathe Bikupe Nkoy; Augustin Tshibwabwa Twabela; Justin Masumu; Steve Ahuka-Mundeke; Jean-Jacques Muyembe-Tamfum; Manabu Igarashi; Eun-sil Park; Shigeru Morikawa; Sheila Makiala-Mandanda; Ayato Takada
    The Lancet Microbe, 5, 6, e529-e537, Elsevier BV, Mar. 2024, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, BACKGROUND: Bas-Congo virus (BASV), an emerging tibrovirus, was associated with an outbreak of acute haemorrhagic fever in Mangala, Democratic Republic of the Congo, in 2009. In 2012, neutralising antibodies to BASV were detected in the lone survivor and one of his close contacts. However, subsequent serological and molecular surveys were unsuccessful as neither BASV antibodies nor its RNA were detected. In this study, we determined the seroprevalence of BASV infection in Mangala 13 years after the initial outbreak. METHODS: We conducted a population-based serological survey from Jan 17 to Jan 23, 2022. Consenting individuals at least 5 years of age, living in Mangala for at least 4 weeks, and who had no contraindication to venepuncture were enrolled. Participants were interviewed using a pre-tested questionnaire for sociodemographic and clinical characteristics. We supplemented the collected serum samples with 284 archived samples from Matadi and Kinshasa. All samples were tested for antibodies to BASV and other tibroviruses using a pseudovirus-based neutralisation test. FINDINGS: Among the 267 individuals from Mangala, the prevalence of BASV antibodies was 55% (95% CI 49-61; n=147). BASV seropositivity odds significantly increased with age (5·2 [95% CI 2·1-12·9] to 83·9 [20·8-337·7] times higher in participants aged 20 years or older than participants aged 5-19 years). Some occupational categories (eg, farmer or public servant) were associated with seropositivity. Only nine (6%) of 160 samples from Matadi and one (<1%) of 124 samples from Kinshasa had neutralising antibodies to BASV. Moreover, we also detected neutralising antibodies to other tibroviruses-Ekpoma virus 1, Ekpoma virus 2, and Mundri virus-in 84 (31%), 251 (94%), and 219 (82%) of 267 Mangala samples; 14 (9%), 62 (39%), and 120 (75%) of 160 Matadi samples; and six (5%), five (4%), and 33 (27%) of 124 Kinshasa samples, respectively. INTERPRETATION: Human infection with BASV and other tibroviruses seems common in Mangala, although no deadly outbreak has been reported since 2009. Exposure to BASV might be highly restricted to Mangala and the increasing prevalence of neutralising antibodies with age suggests regular contact with the virus in this city. Altogether, our findings suggest that human infection with tibroviruses could be common in the study areas and not associated with deadly haemorrhagic or debilitating syndromes. FUNDING: Japan Agency for Medical Research and Development (AMED) and Japan International Cooperation Agency (JICA) under the Science and Technology Research Partnership for Sustainable Development (SATREPS) and Japan Program for Infectious Diseases Research and Infrastructure from AMED.
  • Phylogenetic Analysis of Newcastle Disease Virus Isolated from Poultry in Live Bird Markets and Wild Waterfowl in Zambia.
    Annie Kalonda; Ngonda Saasa; Masahiro Kajihara; Naganori Nao; Ladslav Moonga; Joseph Ndebe; Akina Mori-Kajihara; Andrew Nalishuwa Mukubesa; Yoshihiro Sakoda; Hirofumi Sawa; Ayato Takada; Edgar Simulundu
    Microorganisms, 12, 2, 08 Feb. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Poultry production is essential to the economy and livelihood of many rural Zambian households. However, the industry is threatened by infectious diseases, particularly Newcastle disease virus (NDV) infection. Therefore, this study employed next-generation sequencing to characterise six NDV isolates from poultry in Zambia's live bird markets (LBMs) and wild waterfowl. Four NDV isolates were detected from 410 faecal samples collected from chickens in LBMs in Lusaka and two from 2851 wild birds from Lochinvar National Park. Phylogenetic analysis revealed that the four NDVs from LBM clustered in genotype VII and sub-genotype VII.2 were closely related to viruses previously isolated in Zambia and other Southern African countries, suggesting possible local and regional transboundary circulation of the virus. In contrast, the two isolates from wild birds belonged to class I viruses, genotype 1, and were closely related to isolates from Europe and Asia, suggesting the possible introduction of these viruses from Eurasia, likely through wild bird migration. The fusion gene cleavage site motif for all LBM-associated isolates was 112RRQKR|F117, indicating that the viruses are virulent, while the isolates from wild waterfowl had the typical 112ERQER|L117 avirulent motif. This study demonstrates the circulation of virulent NDV strains in LBMs and has, for the first time, characterised NDV from wild birds in Zambia. The study further provides the first whole genomes of NDV sub-genotype VII.2 and genotype 1 from Zambia and stresses the importance of surveillance and molecular analysis for monitoring the circulation of NDV genotypes and viral evolution.
  • ICTV Virus Taxonomy Profile: Filoviridae 2024.
    Nadine Biedenkopf; Alexander Bukreyev; Kartik Chandran; Nicholas Di Paola; Pierre B H Formenty; Anthony Griffiths; Adam J Hume; Elke Mühlberger; Sergey V Netesov; Gustavo Palacios; Janusz T Pawęska; Sophie Smither; Ayato Takada; Victoria Wahl; Jens H Kuhn
    The Journal of general virology, 105, 2, Feb. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Filoviridae is a family of negative-sense RNA viruses with genomes of about 13.1-20.9 kb that infect fish, mammals and reptiles. The filovirid genome is a linear, non-segmented RNA with five canonical open reading frames (ORFs) that encode a nucleoprotein (NP), a polymerase cofactor (VP35), a glycoprotein (GP1,2), a transcriptional activator (VP30) and a large protein (L) containing an RNA-directed RNA polymerase (RdRP) domain. All filovirid genomes encode additional proteins that vary among genera. Several filovirids (e.g., Ebola virus, Marburg virus) are pathogenic for humans and highly virulent. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Filoviridae, which is available at www.ictv.global/report/filoviridae.
  • Development of an Immunochromatography Assay to Detect Marburg Virus and Ravn Virus
    Katendi Changula; Masahiro Kajihara; Shino Muramatsu; Koji Hiraoka; Toru Yamaguchi; Yoko Yago; Daisuke Kato; Hiroko Miyamoto; Akina Mori-Kajihara; Asako Shigeno; Reiko Yoshida; Corey W. Henderson; Andrea Marzi; Ayato Takada
    Viruses, 15, 12, 2349, 2349, MDPI AG, 29 Nov. 2023, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, The recent outbreaks of Marburg virus disease (MVD) in Guinea, Ghana, Equatorial Guinea, and Tanzania, none of which had reported previous outbreaks, imply increasing risks of spillover of the causative viruses, Marburg virus (MARV) and Ravn virus (RAVV), from their natural host animals. These outbreaks have emphasized the need for the development of rapid diagnostic tests for this disease. Using monoclonal antibodies specific to the viral nucleoprotein, we developed an immunochromatography (IC) assay for the rapid diagnosis of MVD. The IC assay was found to be capable of detecting approximately 102−4 50% tissue culture infectious dose (TCID50)/test of MARV and RAVV in the infected culture supernatants. We further confirmed that the IC assay could detect the MARV and RAVV antigens in the serum samples from experimentally infected nonhuman primates. These results indicate that the IC assay to detect MARV can be a useful tool for the rapid point-of-care diagnosis of MVD.
  • The evolution and determinants of neutralization of potent head-binding antibodies against Ebola virus.
    Xiaoying Yu; Kathryn M Hastie; Carl W Davis; Ruben Diaz Avalos; Dewight Williams; Diptiben Parekh; Sean Hui; Colin Mann; Chitra Hariharan; Ayato Takada; Rafi Ahmed; Erica Ollmann Saphire
    Cell reports, 42, 11, 113366, 113366, 28 Nov. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Monoclonal antibodies against the Ebola virus (EBOV) surface glycoprotein are effective treatments for EBOV disease. Antibodies targeting the EBOV glycoprotein (GP) head epitope have potent neutralization and Fc effector function activity and thus are of high interest as therapeutics and for vaccine design. Here we focus on the head-binding antibodies 1A2 and 1D5, which have been identified previously in a longitudinal study of survivors of EBOV infection. 1A2 and 1D5 have the same heavy- and light-chain germlines despite being isolated from different individuals and at different time points after recovery from infection. Cryoelectron microscopy analysis of each antibody in complex with the EBOV surface GP reveals key amino acid substitutions in 1A2 that contribute to greater affinity, improved neutralization potency, and enhanced breadth as well as two strategies for antibody evolution from a common site.
  • Prevalence and Genomic Characterization of Rotavirus A from Domestic Pigs in Zambia: Evidence for Possible Porcine–Human Interspecies Transmission
    Joseph Ndebe; Hayato Harima; Herman Moses Chambaro; Michihito Sasaki; Junya Yamagishi; Annie Kalonda; Misheck Shawa; Yongjin Qiu; Masahiro Kajihara; Ayato Takada; Hirofumi Sawa; Ngonda Saasa; Edgar Simulundu
    Pathogens, 12, 10, 1199, 1199, MDPI AG, 27 Sep. 2023, [Peer-reviewed]
    English, Scientific journal, Rotavirus is a major cause of diarrhea globally in animals and young children under 5 years old. Here, molecular detection and genetic characterization of porcine rotavirus in smallholder and commercial pig farms in the Lusaka Province of Zambia were conducted. Screening of 148 stool samples by RT-PCR targeting the VP6 gene revealed a prevalence of 22.9% (34/148). Further testing of VP6-positive samples with VP7-specific primers produced 12 positives, which were then Sanger-sequenced. BLASTn of the VP7 positives showed sequence similarity to porcine and human rotavirus strains with identities ranging from 87.5% to 97.1%. By next-generation sequencing, the full-length genetic constellation of the representative strains RVA/pig-wt/ZMB/LSK0137 and RVA/pig-wt/ZMB/LSK0147 were determined. Genotyping of these strains revealed a known Wa-like genetic backbone, and their genetic constellations were G4-P[6]-I5-R1-C1-M1-A8-N1-T1-E1-H1 and G9-P[13]-I5-R1-C1-M1-A8-N1-T1-E1-H1, respectively. Phylogenetic analysis revealed that these two viruses might have their ancestral origin from pigs, though some of their gene segments were related to human strains. The study shows evidence of reassortment and possible interspecies transmission between pigs and humans in Zambia. Therefore, the “One Health” surveillance approach for rotavirus A in animals and humans is recommended to inform the design of effective control measures.
  • ザンビアにおけるブタインフルエンザの疫学調査
    播磨 勇人; 奥谷 公亮; 梶原 将大; 小川 寛人; Simulundu Edgar; Bwalya Eugene; 邱 永晋; 迫田 義博; 西藤 岳彦; Hang' ombe Bernard; 澤 洋文; Mweene Aaron; 高田 礼人
    日本獣医学会学術集会講演要旨集, 166回, 154, 154, (公社)日本獣医学会, Sep. 2023, [Last author]
    Japanese
  • Annual (2023) taxonomic update of RNA-directed RNA polymerase-encoding negative-sense RNA viruses (realm Riboviria: kingdom Orthornavirae: phylum Negarnaviricota).
    Jens H Kuhn; Junya Abe; Scott Adkins; Sergey V Alkhovsky; Tatjana Avšič-Županc; María A Ayllón; Justin Bahl; Anne Balkema-Buschmann; Matthew J Ballinger; Virendra Kumar Baranwal; Martin Beer; Nicolas Bejerman; Éric Bergeron; Nadine Biedenkopf; Carol D Blair; Kim R Blasdell; Arnaud G Blouin; Steven B Bradfute; Thomas Briese; Paul A Brown; Ursula J Buchholz; Michael J Buchmeier; Alexander Bukreyev; Felicity Burt; Carmen Büttner; Charles H Calisher; Mengji Cao; Inmaculada Casas; Kartik Chandran; Rémi N Charrel; Krishna Kumar Chaturvedi; Kar Mun Chooi; Anya Crane; Elena Dal Bó; Juan Carlos de la Torre; William M de Souza; Rik L de Swart; Humberto Debat; Nolwenn M Dheilly; Nicholas Di Paola; Francesco Di Serio; Ralf G Dietzgen; Michele Digiaro; J Felix Drexler; W Paul Duprex; Ralf Dürrwald; Andrew J Easton; Toufic Elbeaino; Koray Ergünay; Guozhong Feng; Andrew E Firth; Anthony R Fooks; Pierre B H Formenty; Juliana Freitas-Astúa; Selma Gago-Zachert; María Laura García; Adolfo García-Sastre; Aura R Garrison; Thomas R Gaskin; Wenjie Gong; Jean-Paul J Gonzalez; JoëlleGoüy de Bellocq; Anthony Griffiths; Martin H Groschup; Ines Günther; Stephan Günther; John Hammond; Yusuke Hasegawa; Kazusa Hayashi; Jussi Hepojoki; Colleen M Higgins; Seiji Hongō; Masayuki Horie; Holly R Hughes; Adam J Hume; Timothy H Hyndman; Kenichi Ikeda; Dàohóng Jiāng; Gilda B Jonson; Sandra Junglen; Boris Klempa; Jonas Klingström; Hideki Kondō; Eugene V Koonin; Mart Krupovic; Kenji Kubota; Gael Kurath; Lies Laenen; Amy J Lambert; Jiànróng Lǐ; Jun-Min Li; Ran Liu; Igor S Lukashevich; Robin M MacDiarmid; Piet Maes; Marco Marklewitz; Sergio H Marshall; Shin-Yi L Marzano; John W McCauley; Ali Mirazimi; Elke Mühlberger; Tomoyuki Nabeshima; Rayapati Naidu; Tomohide Natsuaki; Beatriz Navarro; José A Navarro; Yutaro Neriya; Sergey V Netesov; Gabriele Neumann; Norbert Nowotny; Márcio R T Nunes; Francisco M Ochoa-Corona; Tomoyuki Okada; Gustavo Palacios; Vicente Pallás; Anna Papa; Sofia Paraskevopoulou; Colin R Parrish; Alex Pauvolid-Corrêa; Janusz T Pawęska; Daniel R Pérez; Florian Pfaff; Richard K Plemper; Thomas S Postler; Lee O Rabbidge; Sheli R Radoshitzky; Pedro L Ramos-González; Marius Rehanek; Renato O Resende; Carina A Reyes; Thaís C S Rodrigues; Víctor Romanowski; Dennis Rubbenstroth; Luisa Rubino; Jonathan A Runstadler; Sead Sabanadzovic; Sabrina Sadiq; Maria S Salvato; Takahide Sasaya; Martin Schwemmle; Stephen R Sharpe; Mang Shi; Yoshifumi Shimomoto; Venkidusamy Kavi Sidharthan; Manuela Sironi; Sophie Smither; Jin-Won Song; Kirsten M Spann; Jessica R Spengler; Mark D Stenglein; Ayato Takada; Sawana Takeyama; Akio Tatara; Robert B Tesh; Natalie J Thornburg; Xin Tian; Nicole D Tischler; Yasuhiro Tomitaka; Keizō Tomonaga; Noël Tordo; Changchun Tu; Massimo Turina; Ioannis E Tzanetakis; Anna Maria Vaira; Bernadette van den Hoogen; Bert Vanmechelen; Nikos Vasilakis; Martin Verbeek; Susanne von Bargen; Jiro Wada; Victoria Wahl; Peter J Walker; Thomas B Waltzek; Anna E Whitfield; Yuri I Wolf; Han Xia; Evanthia Xylogianni; Hironobu Yanagisawa; Kazutaka Yano; Gongyin Ye; Zhiming Yuan; F Murilo Zerbini; Guilin Zhang; Song Zhang; Yong-Zhen Zhang; Lu Zhao; Arnfinn Lodden Økland
    The Journal of general virology, 104, 8, Aug. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
  • Surveillance, Isolation, and Genetic Characterization of Bat Herpesviruses in Zambia.
    Hayato Harima; Yongjin Qiu; Junya Yamagishi; Masahiro Kajihara; Katendi Changula; Kosuke Okuya; Mao Isono; Tomoyuki Yamaguchi; Hirohito Ogawa; Naganori Nao; Michihito Sasaki; Edgar Simulundu; Aaron S Mweene; Hirofumi Sawa; Kanako Ishihara; Bernard M Hang'ombe; Ayato Takada
    Viruses, 15, 6, 13 Jun. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Bats are of significant interest as reservoirs for various zoonotic viruses with high diversity. During the past two decades, many herpesviruses have been identified in various bats worldwide by genetic approaches, whereas there have been few reports on the isolation of infectious herpesviruses. Herein, we report the prevalence of herpesvirus infection of bats captured in Zambia and genetic characterization of novel gammaherpesviruses isolated from striped leaf-nosed bats (Macronycteris vittatus). By our PCR screening, herpesvirus DNA polymerase (DPOL) genes were detected in 29.2% (7/24) of Egyptian fruit bats (Rousettus aegyptiacus), 78.1% (82/105) of Macronycteris vittatus, and one Sundevall's roundleaf bat (Hipposideros caffer) in Zambia. Phylogenetic analyses of the detected partial DPOL genes revealed that the Zambian bat herpesviruses were divided into seven betaherpesvirus groups and five gammaherpesvirus groups. Two infectious strains of a novel gammaherpesvirus, tentatively named Macronycteris gammaherpesvirus 1 (MaGHV1), were successfully isolated from Macronycteris vittatus bats, and their complete genomes were sequenced. The genome of MaGHV1 encoded 79 open reading frames, and phylogenic analyses of the DNA polymerase and glycoprotein B demonstrated that MaGHV1 formed an independent lineage sharing a common origin with other bat-derived gammaherpesviruses. Our findings provide new information regarding the genetic diversity of herpesviruses maintained in African bats.
  • Head-to-head comparison of diagnostic accuracy of four Ebola virus disease rapid diagnostic tests versus GeneXpert® in eastern Democratic Republic of the Congo outbreaks: a prospective observational study
    Daniel Mukadi-Bamuleka; Junior Bulabula-Penge; Bart K.M. Jacobs; Anja De Weggheleire; François Edidi-Atani; Fabrice Mambu-Mbika; Anaïs Legand; John D. Klena; Peter N. Fonjungo; Placide Mbala-Kingebeni; Sheila Makiala-Mandanda; Masahiro Kajihara; Ayato Takada; Joel M. Montgomery; Pierre Formenty; Jean-Jacques Muyembe-Tamfum; Kevin K. Ariën; Johan van Griensven; Steve Ahuka-Mundeke; Hgo Kavunga-Membo; Elie Ishara-Nshombo; Stijn Roge; Noella Mulopo-Mukanya; Espérance Tsiwedi-Tsilabia; Emile Muhindo-Milonde; Marie-Anne Kavira-Muhindo; Maria E. Morales-Betoulle; Antoine Nkuba-Ndaye
    eBioMedicine, 91, 104568, 104568, Elsevier BV, May 2023, [Peer-reviewed]
    Scientific journal
  • Structural and energetic basis for differential binding of Ebola and Marburg virus glycoproteins to a bat-derived Niemann-Pick C1 protein.
    Manabu Igarashi; Takatsugu Hirokawa; Ayato Takada
    The Journal of infectious diseases, 29 Apr. 2023, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Our previous study demonstrated that the fruit bat (Yaeyama flying fox)-derived cell line FBKT1 showed preferential susceptibility to Ebola virus (EBOV), whereas the human cell line HEK293T was similarly susceptible to EBOV and Marburg virus (MARV). This was due to three amino acid differences of the endosomal receptor Niemann-Pick C1 (NPC1) between this bat species and humans (i.e., TET and SGA, respectively, at positions 425-427 of NPC1), as well as two specific amino acid differences at positions 87 and 142 of the viral surface glycoprotein (GP) between EBOV and MARV. To understand the contribution of these amino acid differences to intermolecular interactions between NPC1 and GP, we performed molecular dynamics simulations and binding free energy calculations. The average binding free energies of human NPC1 (hNPC1) and its mutant having TET at positions 425-427 (hNPC1/TET) were similar for the interaction with EBOV GP. In contrast, hNPC1/TET had a weaker interaction with MARV GP than wildtype hNPC1. As expected, substitutions of amino acid residues at 87 or 142 in EBOV and MARV GPs converted the binding affinity to hNPC1/TET. Our data provide structural and energetic insights for understanding potential differences in the GP-NPC1 interaction, which could influence the host tropism of EBOV and MARV.
  • Morphogenesis of Bullet-Shaped Rabies Virus Particles Regulated by TSG101.
    Yukari Itakura; Koshiro Tabata; Takeshi Saito; Kittiya Intaruck; Nijiho Kawaguchi; Mai Kishimoto; Shiho Torii; Shintaro Kobayashi; Naoto Ito; Michiko Harada; Satoshi Inoue; Ken Maeda; Ayato Takada; William W Hall; Yasuko Orba; Hirofumi Sawa; Michihito Sasaki
    Journal of virology, 97, 5, e0043823, 12 Apr. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Viral protein assembly and virion budding are tightly regulated to enable the proper formation of progeny virions. At this late stage in the virus life cycle, some enveloped viruses take advantage of the host endosomal sorting complex required for transport (ESCRT) machinery, which contributes to the physiological functions of membrane modulation and abscission. Bullet-shaped viral particles are unique morphological characteristics of rhabdoviruses; however, the involvement of host factors in rhabdovirus infection and, specifically, the molecular mechanisms underlying virion formation are not fully understood. In the present study, we used a small interfering RNA (siRNA) screening approach and found that the ESCRT-I component TSG101 contributes to the propagation of rabies virus (RABV). We demonstrated that the matrix protein (M) of RABV interacts with TSG101 via the late domain containing the PY and YL motifs, which are conserved in various viral proteins. Loss of the YL motif in the RABV M or the downregulation of host TSG101 expression resulted in the intracellular aggregation of viral proteins and abnormal virus particle formation, indicating a defect in the RABV assembly and budding processes. These results indicate that the interaction of the RABV M and TSG101 is pivotal for not only the efficient budding of progeny RABV from infected cells but also for the bullet-shaped virion morphology. IMPORTANCE Enveloped viruses bud from cells with the host lipid bilayer. Generally, the membrane modulation and abscission are mediated by host ESCRT complexes. Some enveloped viruses utilize their late (L-) domain to interact with ESCRTs, which promotes viral budding. Rhabdoviruses form characteristic bullet-shaped enveloped virions, but the underlying molecular mechanisms involved remain elusive. Here, we showed that TSG101, one of the ESCRT components, supports rabies virus (RABV) budding and proliferation. TSG101 interacted with RABV matrix protein via the L-domain, and the absence of this interaction resulted in intracellular virion accumulation and distortion of the morphology of progeny virions. Our study reveals that virion formation of RABV is highly regulated by TSG101 and the virus matrix protein.
  • Surveillance and Phylogenetic Characterisation of Avian Influenza Viruses Isolated from Wild Waterfowl in Zambia in 2015, 2020, and 2021
    Annie Kalonda; Ngonda Saasa; Masahiro Kajihara; Naganori Nao; Ladislav Moonga; Joseph Ndebe; Akina Mori-Kajihara; Andrew Nalishuwa Mukubesa; Mulemba Samutela; Samuel Munjita; Yoshihiro Sakoda; Hirofumi Sawa; Ayato Takada; Edgar Simulundu
    Transboundary and Emerging Diseases, 2023, 1, 16, Hindawi Limited, 01 Mar. 2023, [Peer-reviewed]
    Scientific journal, In recent years, the southern African region has experienced repeated incursions of highly pathogenic avian influenza viruses (HPAIVs), with wild migratory birds being implicated in the spread. To understand the profile of avian influenza viruses (AIVs) circulating in Zambia, we surveyed wild waterfowl for AIVs and phylogenetically characterised the isolates detected in 2015, 2020, and 2021. A total of 2,851 faecal samples of wild waterfowl were collected from Lochinvar National Park in the Southern Province of Zambia. During the study period, 85 (3.0%) low pathogenicity AIVs belonging to various subtypes were isolated, with H2N9, H8N4, and H10N8 being reported for the first time in avian species in Africa. The majority of the isolates were detected from glossy ibis (order Pelecaniformes) making it the first report of AIV from these birds in Zambia. Phylogenetic analysis of all eight gene segments of the 30 full genomes obtained in this study revealed that all the isolates belonged to the Eurasian lineage with their closest relatives being viruses isolated from wild and/or domestic birds in Bangladesh, Belgium, Egypt, Georgia, Mongolia, the Netherlands, and South Africa. Additionally, the Zambian viruses were grouped into distinct clusters based on the year of isolation. While no notifiable AIVs of the H5 or H7 subtypes were detected in wild birds in Zambia, viral internal protein genes of some viruses were closely related to H7 low pathogenicity AIVs. This study shows that periodically, a considerable diversity of AIV subtypes are introduced into the Zambian ecosystem by wild migratory waterfowl. The findings highlight the importance of continuous surveillance and monitoring of AIVs in wild waterfowl, including birds traditionally not considered to be major AIV reservoirs, for a better understanding of the eco-epidemiology and evolutionary dynamics of AIVs in Africa.
  • Detection of Old and New World Relapsing Fever Borreliae in Ornithodoros Ticks Collected from Warthog Burrows in Zambia.
    Yongjin Qiu; Herman M Chambaro; Kozue Sato; David Squarre; Edgar Simulundu; Masahiro Kajihara; Katendi Changula; Manyando Simbotwe; Hayato Harima; Joseph Ndebe; Ladslav Moonga; Ryo Nakao; Ayato Takada; Bernard Mudenda Hang'ombe; Hirofumi Sawa; Hiroki Kawabata
    Microorganisms, 11, 1, 12 Jan. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Relapsing fever (RF) is an arthropod-borne disease caused by Borrelia spirochete, which is one of the major public health concerns in endemic regions including Africa. However, information on Borrelia&nbsp;spirochetes is limited in Zambia. Here, we investigate the Borrelia&nbsp;spirochetes harbored by Ornithodoros ticks in Zambian National Parks. We analyzed 182 DNA samples pooled from 886 Ornithodoros ticks. Of these, 43 tested positive, and their sequence revealed that the ticks harbored both Old and New World RF borreliae. This research presents the first evidence of Old-World RF borreliae in Zambia. The New World RF borreliae detected herein differed from the Candidatus Borrelia fainii previously reported in Zambia and were closely related to the pathogenic Borrelia sp. VS4 identified in Tanzania. Additionally, Borrelia theileri was recently reported in Zambia. Hence, at least four different Borrelia species occur in Zambia, and the organisms causing relapsing fever there might be more complex than previously thought. We empirically confirmed that real-time PCR with TaqMan minor groove binder probes accurately and simultaneously detected both Old and New World RF. In this manner, they could facilitate quantitative analyses of both types of RF borreliae. Subsequent investigations should endeavor to isolate the aforementioned Borrelia spp. and perform serosurveys on patients with RF.
  • Current status and molecular epidemiology of rabies virus from different hosts and regions in Malawi.
    Henson Kainga; Elisha Chatanga; Marvin Collen Phonera; John Pilate Kothowa; Precious Dzimbiri; Gladson Kamwendo; Malala Mulavu; Cynthia Sipho Khumalo; Katendi Changula; Herman Chambaro; Hayato Harima; Masahiro Kajihara; Kholiwe Mkandawire; Patrick Chikungwa; Julius Chulu; Gilson Njunga; Simbarashe Chitanga; Benjamin Mubemba; Michihito Sasaki; Yasuko Orba; Yongjin Qiu; Junya Yamagishi; Edgar Simulundu; Ayato Takada; Boniface Namangala; Hirofumi Sawa; Walter Muleya
    Archives of virology, 168, 2, 61, 61, 12 Jan. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Although rabies is endemic in Malawi, there have been no studies in which rabies virus was systematically investigated and characterized in multiple animal hosts in that country. In order to provide molecular epidemiological data on rabies virus in Malawi, 683 suspected rabies case reports from 2008 to 2021 were examined, and 46 (dog = 40, cow = 5, and cat = 1) viable rabies-positive brain samples archived at the Central Veterinary Laboratory (CVL), Lilongwe, Malawi, were analyzed genetically. The results showed an increase in the submission of brain samples from 2008 to 2010, with the highest number of submissions observed in 2020. Of the 683 case reports analyzed for the period under review, 38.1% (260/683) (CI: 34.44 - 41.84) were confirmed by direct fluorescent antibody test. Among the confirmed cases, 65.4% (170/260) (CI: 59.23 - 71.09) were canine rabies. Further, phylogenetic analysis revealed that sequences from different animal hosts clustered together within the Africa 1b lineage, suggesting that the strains circulating in livestock are similar to those in domestic dogs. This finding supports the hypothesis that canine rabies is spilling over to livestock and emphasizes the need for further studies to provide data for effective control of rabies in Malawi.
  • Isolation and Characterization of Distinct Rotavirus A in Bat and Rodent Hosts.
    Mai Kishimoto; Masahiro Kajihara; Koshiro Tabata; Yukari Itakura; Shinsuke Toba; Seiya Ozono; Yuko Sato; Tadaki Suzuki; Naoto Ito; Katendi Changula; Yongjin Qiu; Akina Mori-Kajihara; Yoshiki Eto; Hayato Harima; Daniel Mwizabi; Bernard M Hang'ombe; William W Hall; Ayato Takada; Yasuko Orba; Hirofumi Sawa; Michihito Sasaki
    Journal of virology, 97, 1, e0145522, 12 Jan. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Rotavirus A (RVA) causes diarrheal disease in humans and various animals. Recent studies have identified bat and rodent RVAs with evidence of zoonotic transmission and genome reassortment. However, the virological properties of bat and rodent RVAs with currently identified genotypes still need to be better clarified. Here, we performed virus isolation-based screening for RVA in animal specimens and isolated RVAs (representative strains: 16-06 and MpR12) from Egyptian fruit bat and Natal multimammate mouse collected in Zambia. Whole-genome sequencing and phylogenetic analysis revealed that the genotypes of bat RVA 16-06 were identical to that of RVA BATp39 strain from the Kenyan fruit bat, which has not yet been characterized. Moreover, all segments of rodent RVA MpR12 were highly divergent and assigned to novel genotypes, but RVA MpR12 was phylogenetically closer to bat RVAs than to other rodent RVAs, indicating a unique evolutionary history. We further investigated the virological properties of the isolated RVAs. In brief, we found that 16-06 entered cells by binding to sialic acids on the cell surface, while MpR12 entered in a sialic acid-independent manner. Experimental inoculation of suckling mice with 16-06 and MpR12 revealed that these RVAs are causative agents of diarrhea. Moreover, 16-06 and MpR12 demonstrated an ability to infect and replicate in a 3D-reconstructed primary human intestinal epithelium with comparable efficiency to the human RVA. Taken together, our results detail the unique genetic and virological features of bat and rodent RVAs and demonstrate the need for further investigation of their zoonotic potential. IMPORTANCE Recent advances in nucleotide sequence detection methods have enabled the detection of RVA genomes from various animals. These studies have discovered multiple divergent RVAs and have resulted in proposals for the genetic classification of novel genotypes. However, most of these RVAs have been identified via dsRNA viral genomes and not from infectious viruses, and their virological properties, such as cell/host tropisms, transmissibility, and pathogenicity, are unclear and remain to be clarified. Here, we successfully isolated RVAs with novel genome constellations from three bats and one rodent in Zambia. In addition to whole-genome sequencing, the isolated RVAs were characterized by glycan-binding affinity, pathogenicity in mice, and infectivity to the human gut using a 3D culture of primary intestinal epithelium. Our study reveals the first virological properties of bat and rodent RVAs with high genetic diversity and unique evolutional history and provides basic knowledge to begin estimating the potential of zoonotic transmission.
  • Susceptibility of common dabbling and diving duck species to clade 2.3.2.1 H5N1 high pathogenicity avian influenza virus: an experimental infection study
    Kosuke SODA; Yukiko TOMIOKA; Tatsufumi USUI; Hiroichi OZAKI; Hiroshi ITO; Yasuko NAGAI; Naoki YAMAMOTO; Masatoshi OKAMATSU; Norikazu ISODA; Masahiro KAJIHARA; Yoshihiro SAKODA; Ayato TAKADA; Toshihiro ITO
    Journal of Veterinary Medical Science, 85, 9, 942, 949, Japanese Society of Veterinary Science, 2023, [Peer-reviewed]
    Scientific journal
  • Field-deployable multiplex detection method of SARS-CoV-2 and influenza virus using loop-mediated isothermal amplification and DNA chromatography.
    Kyoko Hayashida; Alejandro Garcia; Lavel Chinyama Moonga; Tatsuki Sugi; Kodera Takuya; Mitsuo Kawase; Fumihiro Kodama; Atsushi Nagasaka; Nobuhisa Ishiguro; Ayato Takada; Masahiro Kajihara; Naganori Nao; Masashi Shingai; Hiroshi Kida; Yasuhiko Suzuki; William W Hall; Hirofumi Sawa; Junya Yamagishi
    PloS one, 18, 5, e0285861, 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, A novel multiplex loop-mediated isothermal amplification (LAMP) method combined with DNA chromatography was developed for the simultaneous detection of three important respiratory disease-causing viruses: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus. Amplification was performed at a constant temperature, and a positive result was confirmed by a visible colored band. An in-house drying protocol with trehalose was used to prepare the dried format multiplex LAMP test. Using this dried multiplex LAMP test, the analytical sensitivity was determined to be 100 copies for each viral target and 100-1000 copies for the simultaneous detection of mixed targets. The multiplex LAMP system was validated using clinical COVID-19 specimens and compared with the real-time qRT-PCR method as a reference test. The determined sensitivity of the multiplex LAMP system for SARS-CoV-2 was 71% (95% CI: 0.62-0.79) for cycle threshold (Ct) ≤ 35 samples and 61% (95% CI: 0.53-0.69) for Ct ≤40 samples. The specificity was 99% (95%CI: 0.92-1.00) for Ct ≤35 samples and 100% (95%CI: 0.92-1.00) for the Ct ≤40 samples. The developed simple, rapid, low-cost, and laboratory-free multiplex LAMP system for the two major important respiratory viral diseases, COVID-19 and influenza, is a promising field-deployable diagnosis tool for the possible future 'twindemic, ' especially in resource-limited settings.
  • 2022 taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales
    Jens H. Kuhn; Scott Adkins; Sergey V. Alkhovsky; Tatjana Avšič-Županc; María A. Ayllón; Justin Bahl; Anne Balkema-Buschmann; Matthew J. Ballinger; Martina Bandte; Martin Beer; Nicolas Bejerman; Éric Bergeron; Nadine Biedenkopf; Laurent Bigarré; Carol D. Blair; Kim R. Blasdell; Steven B. Bradfute; Thomas Briese; Paul A. Brown; Rémy Bruggmann; Ursula J. Buchholz; Michael J. Buchmeier; Alexander Bukreyev; Felicity Burt; Carmen Büttner; Charles H. Calisher; Thierry Candresse; Jeremy Carson; Inmaculada Casas; Kartik Chandran; Rémi N. Charrel; Yuya Chiaki; Anya Crane; Mark Crane; Laurent Dacheux; Elena Dal Bó; Juan Carlos de la Torre; Xavier de Lamballerie; William M. de Souza; Rik L. de Swart; Nolwenn M. Dheilly; Nicholas Di Paola; Francesco Di Serio; Ralf G. Dietzgen; Michele Digiaro; J. Felix Drexler; W. Paul Duprex; Ralf Dürrwald; Andrew J. Easton; Toufic Elbeaino; Koray Ergünay; Guozhong Feng; Claudette Feuvrier; Andrew E. Firth; Anthony R. Fooks; Pierre B. H. Formenty; Juliana Freitas-Astúa; Selma Gago-Zachert; María Laura García; Adolfo García-Sastre; Aura R. Garrison; Scott E. Godwin; Jean-Paul J. Gonzalez; Joëlle Goüy de Bellocq; Anthony Griffiths; Martin H. Groschup; Stephan Günther; John Hammond; Jussi Hepojoki; Melanie M. Hierweger; Seiji Hongō; Masayuki Horie; Hidenori Horikawa; Holly R. Hughes; Adam J. Hume; Timothy H. Hyndman; Dàohóng Jiāng; Gilda B. Jonson; Sandra Junglen; Fujio Kadono; David G. Karlin; Boris Klempa; Jonas Klingström; Michel C. Koch; Hideki Kondō; Eugene V. Koonin; Jarmila Krásová; Mart Krupovic; Kenji Kubota; Ivan V. Kuzmin; Lies Laenen; Amy J. Lambert; Jiànróng Lǐ; Jun-Min Li; François Lieffrig; Igor S. Lukashevich; Dongsheng Luo; Piet Maes; Marco Marklewitz; Sergio H. Marshall; Shin-Yi L. Marzano; John W. McCauley; Ali Mirazimi; Peter G. Mohr; Nick J. G. Moody; Yasuaki Morita; Richard N. Morrison; Elke Mühlberger; Rayapati Naidu; Tomohide Natsuaki; José A. Navarro; Yutaro Neriya; Sergey V. Netesov; Gabriele Neumann; Norbert Nowotny; Francisco M. Ochoa-Corona; Gustavo Palacios; Laurane Pallandre; Vicente Pallás; Anna Papa; Sofia Paraskevopoulou; Colin R. Parrish; Alex Pauvolid-Corrêa; Janusz T. Pawęska; Daniel R. Pérez; Florian Pfaff; Richard K. Plemper; Thomas S. Postler; Françoise Pozet; Sheli R. Radoshitzky; Pedro L. Ramos-González; Marius Rehanek; Renato O. Resende; Carina A. Reyes; Víctor Romanowski; Dennis Rubbenstroth; Luisa Rubino; Artemis Rumbou; Jonathan A. Runstadler; Melanie Rupp; Sead Sabanadzovic; Takahide Sasaya; Heike Schmidt-Posthaus; Martin Schwemmle; Torsten Seuberlich; Stephen R. Sharpe; Mang Shi; Manuela Sironi; Sophie Smither; Jin-Won Song; Kirsten M. Spann; Jessica R. Spengler; Mark D. Stenglein; Ayato Takada; Robert B. Tesh; Jana Těšíková; Natalie J. Thornburg; Nicole D. Tischler; Yasuhiro Tomitaka; Keizō Tomonaga; Noël Tordo; Kenta Tsunekawa; Massimo Turina; Ioannis E. Tzanetakis; Anna Maria Vaira; Bernadette van den Hoogen; Bert Vanmechelen; Nikos Vasilakis; Martin Verbeek; Susanne von Bargen; Jiro Wada; Victoria Wahl; Peter J. Walker; Anna E. Whitfield; John V. Williams; Yuri I. Wolf; Junki Yamasaki; Hironobu Yanagisawa; Gongyin Ye; Yong-Zhen Zhang; Arnfinn Lodden Økland
    Archives of Virology, 167, 12, 2857, 2906, Springer Science and Business Media LLC, 28 Nov. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, In March 2022, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by two new families (bunyaviral Discoviridae and Tulasviridae), 41 new genera, and 98 new species. Three hundred forty-nine species were renamed and/or moved. The accidentally misspelled names of seven species were corrected. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
  • Luna Virus and Helminths in Wild Mastomys natalensis in Two Contrasting Habitats in Zambia: Risk Factors and Evidence of Virus Dissemination in Semen.
    Samuel Munalula Munjita; Given Moonga; Andrew Nalishuwa Mukubesa; Joseph Ndebe; Benjamin Mubemba; Manu Vanaerschot; Cristina Tato; John Tembo; Nathan Kapata; Simbarashe Chitanga; Katendi Changula; Mashiro Kajihara; Walter Muleya; Ayato Takada; Elisabeth Fichet-Calvet; Alimuddin Zumla; Hirofumi Sawa; Matthew Bates; Sody Munsaka; Edgar Simulundu
    Pathogens (Basel, Switzerland), 11, 11, 14 Nov. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Transmission dynamics and the maintenance of mammarenaviruses in nature are poorly understood. Using metagenomic next-generation sequencing (mNGS) and RT-PCR, we investigated the presence of mammarenaviruses and co-infecting helminths in various tissues of 182 Mastomys natalensis rodents and 68 other small mammals in riverine and non-riverine habitats in Zambia. The Luna virus (LUAV) genome was the only mammarenavirus detected (7.7%; 14/182) from M. natalensis. Only one rodent from the non-riverine habitat was positive, while all six foetuses from one pregnant rodent carried LUAV. LUAV-specific mNGS reads were 24-fold higher in semen than in other tissues from males. Phylogenetically, the viruses were closely related to each other within the LUAV clade. Helminth infections were found in 11.5% (21/182) of M. natalensis. LUAV-helminth co-infections were observed in 50% (7/14) of virus-positive rodents. Juvenility (OR = 9.4; p = 0.018; 95% CI: 1.47-59.84), nematodes (OR = 15.5; p = 0.001; 95% CI: 3.11-76.70), cestodes (OR = 10.8; p = 0.025; 95% CI: 1.35-86.77), and being male (OR = 4.6; p = 0.036; 95% CI: 1.10-18.90) were associated with increased odds of LUAV RNA detection. The role of possible sexual and/or congenital transmission in the epidemiology of LUAV infections in rodents requires further study, along with the implications of possible helminth co-infection.
  • Seroprevalence and Associated Risk Factors of Rift Valley Fever in Livestock from Three Ecological Zones of Malawi.
    Henson Kainga; Marvin Collen Phonera; Elisha Chatanga; Simegnew Adugna Kallu; Prudence Mpundu; Mulemba Samutela; Herman Moses Chambaro; Masahiro Kajihara; Doreen Mainza Shempela; Jay Sikalima; Walter Muleya; Misheck Shawa; Julius Chulu; Gilson Njunga; Martin Simuunza; Ayato Takada; Hirofumi Sawa; Edgar Simulundu; Ngonda Saasa
    Pathogens (Basel, Switzerland), 11, 11, 14 Nov. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The epidemiology of Rift Valley fever (RVF) is poorly understood in Malawi. Here, a cross-sectional study was conducted (March-June 2020) to investigate the seroprevalence and potential risk factors of RVF virus (RVFV) in cattle, goats, and sheep in three ecological zones of Malawi. A total of 1523 serum samples were tested for anti-RVFV IgG and IgM antibodies by ELISA. Additionally, a questionnaire survey was used to assess potential RVF risk factors. The overall seroprevalence was 17.14% (261/1523; 95% CI = 15.33-19.11) for individual livestock and 33.24% (120/361; 95% CI = 28.18-38.11) for the livestock herd. Seroprevalence was significantly high in sheep (25.68%, 95% CI = 19.31-33.26) compared with cattle (21.35%, 95% CI = 18.74-24.22) and goats (7.72%, 95% CI = 5.72-10.34), (p = 0.047). At the individual livestock level, the risk was elevated in female livestock (OR: 1.74, 95% CI = 1.08-12.82) (p = 0.016), while at the herd level, areas receiving approximately 1001-1500 mm of rainfall (OR: 2.47, 95% CI = 1.14-5.37) (p = 0.022), areas of rainfall amount greater than approximately 1600 mm (OR: 2.239, 95% CI = 1.07-8.82) (p = 0.023), and mixed species herds (OR: 10.410, 95% CI = 3.04-35.59) (p = 0.001), were significant risk factors. The detection of IgM antibodies confirmed active circulation of RVFV in Malawi. Therefore, monitoring of RVF in animals, humans, and vectors using a "One Health" approach, along with community sensitization among the high-risk populations, could help mitigate the threat posed by this zoonotic disease in Malawi.
  • Experimental and natural infections of white-tailed sea eagles (Haliaeetus albicilla) with high pathogenicity avian influenza virus of H5 subtype
    Yoshikazu Fujimoto; Kohei Ogasawara; Norikazu Isoda; Hitoshi Hatai; Kosuke Okuya; Yukiko Watanabe; Ayato Takada; Yoshihiro Sakoda; Keisuke Saito; Makoto Ozawa
    Frontiers in Microbiology, 13, Frontiers Media SA, 03 Oct. 2022, [Peer-reviewed]
    English, Scientific journal, White-tailed sea eagle (Haliaeetus albicilla), a regionally rare species of raptor, is threatened in several countries. To assess the risk of H5 high pathogenicity avian influenza (HPAI) viral infection in rare bird species, we performed experimental infections with a GS/GD96-lineage H5N6 HPAI virus of clade 2.3.4.4e in white-tailed sea eagles. Additionally, during the winter of 2020–2021 in Japan, we accidentally encountered a white-tailed sea eagle that had a fatal outcome due to natural infection with a GS/GD96-lineage H5N8 HPAI virus of clade 2.3.4.4b, allowing us to compare experimental and natural infections in the same rare raptor species. Our experiments demonstrated the susceptibility of white-tailed sea eagles to the GS/GD96-lineage H5 HPAI virus with efficient replication in systemic organs. The potential for the viruses to spread within the white-tailed sea eagle population through indirect transmission was also confirmed. Comprehensive comparisons of both viral distribution and histopathological observations between experimentally and naturally infected white-tailed sea eagles imply that viral replication in the brain is responsible for the disease severity and mortality in this species. These findings provide novel insights into the risk assessment of H5 HPAI viral infection in white-tailed sea eagles, proper diagnostic procedures, potential risks to artificially fed eagle populations and persons handling superficially healthy eagles, potential impact of intragastric infection on eagle outcomes, and possibility of severity of the disease being attributed to viral replication in the brain.
  • Molecular characterisation of a novel avian rotavirus A strain detected from a gull species (Larus sp.).
    Yuji Fujii; Tatsunori Masatani; Shoko Nishiyama; Misuzu Okajima; Fumiki Izumi; Katsunori Okazaki; Yoshihiro Sakoda; Ayato Takada; Makoto Ozawa; Makoto Sugiyama; Naoto Ito
    The Journal of general virology, 103, 10, Oct. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, A recent study demonstrated the possibility that migratory birds are responsible for the global spread of avian rotavirus A (RVA). However, little is known about what types of RVAs are retained in migratory birds. In this study, to obtain information on RVA strains in migratory birds, we characterised an RVA strain, Ho374, that was detected in a faecal sample from a gull species (Larus sp.). Genetic analysis revealed that all 11 genes of this strain were classified as new genotypes (G28-P[39]-I21-R14-C14-M13-A24-N14-T16-E21-H16). This clearly indicates that the genetic diversity of avian RVAs is greater than previously recognised. Our findings highlight the need for investigations of RVA strains retained in migratory birds, including gulls.
  • Single Nucleotide Variants of the Human TIM-1 IgV Domain with Reduced Ability to Promote Viral Entry into Cells
    Takanari Hattori; Takeshi Saito; Hiroko Miyamoto; Masahiro Kajihara; Manabu Igarashi; Ayato Takada
    Viruses, 14, 10, 2124, 2124, MDPI AG, 26 Sep. 2022, [Peer-reviewed], [Last author, Corresponding author]
    Scientific journal, Human T-cell immunoglobulin mucin 1 (hTIM-1) is known to promote cellular entry of enveloped viruses. Previous studies suggested that the polymorphisms of hTIM-1 affected its function. Here, we analyzed single nucleotide variants (SNVs) of hTIM-1 to determine their ability to promote cellular entry of viruses using pseudotyped vesicular stomatitis Indiana virus (VSIV). We obtained hTIM-1 sequences from a public database (Ensembl genome browser) and identified 35 missense SNVs in 3 loops of the hTIM-1 immunoglobulin variable (IgV) domain, which had been reported to interact with the Ebola virus glycoprotein (GP) and phosphatidylserine (PS) in the viral envelope. HEK293T cells transiently expressing wildtype hTIM-1 or its SNV mutants were infected with VSIVs pseudotyped with filovirus or arenavirus GPs, and their infectivities were compared. Eleven of the thirty-five SNV substitutions reduced the efficiency of hTIM-1-mediated entry of pseudotyped VSIVs. These SNV substitutions were found not only around the PS-binding pocket but also in other regions of the molecule. Taken together, our findings suggest that some SNVs of the hTIM-1 IgV domain have impaired ability to interact with PS and/or viral GPs in the viral envelope, which may affect the hTIM-1 function to promote viral entry into cells.
  • Detection of anti-ebolavirus antibodies in Ghanaian pigs.
    Hirohito Ogawa; Kenji Ohya; Raphael Ayizanga; Hiroko Miyamoto; Asako Shigeno; Masao Yamada; Yasuhiro Takashima; Miho Inoue-Murayama; Ayato Takada; Boniface Baboreka Kayang
    The Journal of veterinary medical science, 20 Sep. 2022, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Some filoviruses such as ebolaviruses and marburgviruses, cause hemorrhagic fever in humans and nonhuman primates. Pigs are suggested to play a potential role in the filovirus ecology. We investigated the seroprevalence of filovirus infection in pigs in Ghana. Using a viral glycoprotein (GP)-based enzyme-linked immunosorbent assay, we detected filovirus-specific immunoglobulin G antibodies in 5 of 139 samples. These positive sera showed specificities to four different filovirus species. Particularly, two of the positive sera reacted to GPs of two African ebolaviruses (i.e., Ebola virus and Taï Forest virus) in Western blotting. Our results suggest that these Ghanaian pigs were exposed to multiple filoviruses and emphasize the importance of continuous monitoring of filovirus infection in pig populations in West African countries.
  • Genomic Surveillance of SARS-CoV-2 in the Southern Province of Zambia: Detection and Characterization of Alpha, Beta, Delta, and Omicron Variants of Concern.
    Ben Katowa; Annie Kalonda; Benjamin Mubemba; Japhet Matoba; Doreen Mainza Shempela; Jay Sikalima; Boniface Kabungo; Katendi Changula; Simbarashe Chitanga; Mpanga Kasonde; Otridah Kapona; Nathan Kapata; Kunda Musonda; Mwaka Monze; John Tembo; Matthew Bates; Alimuddin Zumla; Catherine G Sutcliffe; Masahiro Kajihara; Junya Yamagishi; Ayato Takada; Hirofumi Sawa; Roma Chilengi; Victor Mukonka; Walter Muleya; Edgar Simulundu
    Viruses, 14, 9, 24 Aug. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have significantly impacted the global epidemiology of the pandemic. From December 2020 to April 2022, we conducted genomic surveillance of SARS-CoV-2 in the Southern Province of Zambia, a region that shares international borders with Botswana, Namibia, and Zimbabwe and is a major tourist destination. Genetic analysis of 40 SARS-CoV-2 whole genomes revealed the circulation of Alpha (B.1.1.7), Beta (B.1.351), Delta (AY.116), and multiple Omicron subvariants with the BA.1 subvariant being predominant. Whereas Beta, Delta, and Omicron variants were associated with the second, third, and fourth pandemic waves, respectively, the Alpha variant was not associated with any wave in the country. Phylogenetic analysis showed evidence of local transmission and possible multiple introductions of SARS-CoV-2 VOCs in Zambia from different European and African countries. Across the 40 genomes analysed, a total of 292 mutations were observed, including 182 missense mutations, 66 synonymous mutations, 23 deletions, 9 insertions, 1 stop codon, and 11 mutations in the non-coding region. This study stresses the need for the continued monitoring of SARS-CoV-2 circulation in Zambia, particularly in strategically positioned regions such as the Southern Province which could be at increased risk of introduction of novel VOCs.
  • Human ACE2 Genetic Polymorphism Affecting SARS-CoV and SARS-CoV-2 Entry into Cells
    Takanari Hattori; Takeshi Saito; Kosuke Okuya; Yuji Takahashi; Hiroko Miyamoto; Masahiro Kajihara; Manabu Igarashi; Ayato Takada
    Microbiology Spectrum, 10, 4, e0087022, American Society for Microbiology, 11 Jul. 2022, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal, SARS-CoV and SARS-CoV-2 are known to cause severe pneumonia in humans. The S protein of these CoVs binds to the ACE2 molecule on the plasma membrane and mediates virus entry into cells.
  • Field performance of three Ebola rapid diagnostic tests used during the 2018–20 outbreak in the eastern Democratic Republic of the Congo: a retrospective, multicentre observational study
    Daniel Mukadi-Bamuleka; Junior Bulabula-Penge; Anja De Weggheleire; Bart K M Jacobs; François Edidi-Atani; Fabrice Mambu-Mbika; Placide Mbala-Kingebeni; Sheila Makiala-Mandanda; Martin Faye; Cheick T Diagne; Moussa M Diagne; Oumar Faye; Masahiro Kajihara; Ousmane Faye; Ayato Takada; Amadou A Sall; Jean-Jacques Muyembe-Tamfum; Johan van Griensven; Kevin K Ariën; Steve Ahuka-Mundeke
    The Lancet Infectious Diseases, 22, 6, 891, 900, Elsevier BV, Jun. 2022, [Peer-reviewed]
    Scientific journal
  • Influenza A Virus Infection in Domestic Ferrets.
    Yudai Kuroda; Ai Okada; Hiroshi Shimoda; Yasutsugu Miwa; Akiko Watamori; Hiroho Ishida; Shin Murakami; Ayato Takada; Taisuke Horimoto; Ken Maeda
    Japanese journal of infectious diseases, 75, 3, 325, 327, 24 May 2022, [Peer-reviewed], [Invited], [Domestic magazines]
    English, Scientific journal, Ferrets are animals that are known to be susceptible to influenza A virus (IAV) infection. To evaluate the risk of IAV transmission from diseased ferrets to humans, we performed a serosurvey to detect specific antibodies against the H1, H3, H5, and H7 subtypes of IAV. We found a high positive rate of the H1 (24.1%) and H3 (5.2%) subtypes in pet ferrets by using an enzyme-linked immunosorbent assay for hemagglutinin proteins. The results were confirmed by the virus-neutralization test for representative antibody-positive serum samples. We also detected hemagglutinin and neuraminidase genes in two ferrets showing acute respiratory illness and whose owner was diagnosed with IAV infection; a human H1N1pdm virus was isolated from one of these ferrets. Our findings suggest that attention should be paid for IAV infection from humans to ferrets, and vice versa.
  • Detection of Tick-Borne Bacterial and Protozoan Pathogens in Ticks from the Zambia-Angola Border.
    Yongjin Qiu; Martin Simuunza; Masahiro Kajihara; Joseph Ndebe; Ngonda Saasa; Penjani Kapila; Hayato Furumoto; Alice C C Lau; Ryo Nakao; Ayato Takada; Hirofumi Sawa
    Pathogens (Basel, Switzerland), 11, 5, 10 May 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Tick-borne diseases (TBDs), including emerging and re-emerging zoonoses, are of public health importance worldwide; however, TBDs tend to be overlooked, especially in countries with fewer resources, such as Zambia and Angola. Here, we investigated Rickettsia, Anaplasmataceae, and Apicomplexan pathogens in 59 and 96 adult ticks collected from dogs and cattle, respectively, in Shangombo, a town at the Zambia-Angola border. We detected Richkettsia africae and Rickettsia aeschilimannii in 15.6% of Amblyomma variegatum and 41.7% of Hyalomma truncatum ticks, respectively. Ehrlichia minasensis was detected in 18.8% of H. truncatum, and Candidatus Midichloria mitochondrii was determined in Hyalomma marginatum. We also detected Babesia caballi and Theileria velifera in A. variegatum ticks with a 4.4% and 6.7% prevalence, respectively. In addition, Hepatozoon canis was detected in 6.5% of Rhipicephalus lunulatus and 4.3% of Rhipicephalus sanguineus. Coinfection of R. aeshilimannii and E. minasensis were observed in 4.2% of H. truncatum. This is the first report of Ca. M. mitochondrii and E. minasensis, and the second report of B. caballi, in the country. Rickettsia africae and R. aeschlimannii are pathogenic to humans, and E. minasensis, B. caballi, T. velifera, and H. canis are pathogenic to animals. Therefore, individuals, clinicians, veterinarians, and pet owners should be aware of the distribution of these pathogens in the area.
  • Gargling with povidone iodine has a short-term inhibitory effect on SARS-CoV-2 in patients with COVID-19
    T. Seikai; A. Takada; A. Hasebe; M. Kajihara; K. Okuya; T. Sekiguchi (Yamada); W. Kakuguchi; S. Konno; Y. Ohiro
    Journal of Hospital Infection, 123, 179, 181, Elsevier BV, May 2022, [Peer-reviewed]
    English, Scientific journal
  • Multiple Routes of Antibody-Dependent Enhancement of SARS-CoV-2 Infection.
    Kosuke Okuya; Takanari Hattori; Takeshi Saito; Yoshihiro Takadate; Michihito Sasaki; Wakako Furuyama; Andrea Marzi; Yoichi Ohiro; Satoshi Konno; Takeshi Hattori; Ayato Takada
    Microbiology spectrum, 10, 2, e0155321, 27 Apr. 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Antibody-dependent enhancement (ADE) of infection is generally known for many viruses. A potential risk of ADE in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has also been discussed since the beginning of the coronavirus disease 2019 (COVID-19) pandemic; however, clinical evidence of the presence of antibodies with ADE potential is limited. Here, we show that ADE antibodies are produced by SARS-CoV-2 infection and the ADE process can be mediated by at least two different host factors, Fcγ receptor (FcγR) and complement component C1q. Of 89 serum samples collected from acute or convalescent COVID-19 patients, 62.9% were found to be positive for SARS-CoV-2-specific IgG. FcγR- and/or C1q-mediated ADE were detected in 50% of the IgG-positive sera, whereas most of them showed neutralizing activity in the absence of FcγR and C1q. Importantly, ADE antibodies were found in 41.4% of the acute COVID-19 patients. Neutralizing activity was also detected in most of the IgG-positive sera, but it was counteracted by ADE in subneutralizing conditions in the presence of FcγR or C1q. Although the clinical importance of ADE needs to be further investigated with larger numbers of COVID-19 patient samples, our data suggest that SARS-CoV-2 utilizes multiple mechanisms of ADE. C1q-mediated ADE may particularly have a clinical impact since C1q is present at high concentrations in plasma and its receptors are ubiquitously expressed on the surfaces of many types of cells, including respiratory epithelial cells, which SARS-CoV-2 primarily infects. IMPORTANCE Potential risks of antibody-dependent enhancement (ADE) in the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been discussed and the proposed mechanism mostly depends on the Fc gamma receptor (FcγR). However, since FcγRs are exclusively expressed on immune cells, which are not primary targets of SARS-CoV-2, the clinical importance of ADE of SARS-CoV-2 infection remains controversial. Our study demonstrates that SARS-CoV-2 infection induces antibodies that increase SARS-CoV-2 infection through another ADE mechanism in which complement component C1q mediates the enhancement. Although neutralizing activity was also detected in the serum samples, it was counteracted by ADE in the presence of FcγR or C1q. Considering the ubiquity of C1q and its cellular receptors, C1q-mediated ADE may more likely occur in respiratory epithelial cells, which SARS-CoV-2 primarily infects. Our data highlight the importance of careful monitoring of the antibody properties in COVID-19 convalescent and vaccinated individuals.
  • Susceptibility of herons (family: Ardeidae) to clade 2.3.2.1 H5N1 subtype high pathogenicity avian influenza virus.
    Kosuke Soda; Yukiko Tomioka; Tatsufumi Usui; Yukiko Uno; Yasuko Nagai; Hiroshi Ito; Takahiro Hiono; Tomokazu Tamura; Masatoshi Okamatsu; Masahiro Kajihara; Naganori Nao; Yoshihiro Sakoda; Ayato Takada; Toshihiro Ito
    Avian pathology : journal of the W.V.P.A, 51, 2, 146, 153, Apr. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The pathogenicity of the H5 subtype high pathogenicity avian influenza viruses (HPAIVs) in Ardeidae bird species has not been investigated yet, despite the increasing infections reported. Therefore, the present study aimed to examine the susceptibility of the Ardeidae species, which had already been reported to be susceptible to HPAIVs, to a clade 2.3.2.1 H5N1 HPAIV. Juvenile herons (four grey herons, one intermediate egret, two little egrets, and three black-crowned night herons) were intranasally inoculated with 106 50% egg infectious dose of the virus and observed for 10 days. Two of the four grey herons showed lethargy and conjunctivitis; among them, one died at 6 days post-inoculation (dpi). The viruses were transmitted to the other two cohoused naïve grey herons. Some little egrets and black-crowned night herons showing neurological disorders died at 4-5 dpi; these birds mainly shed the virus via the oral route. The viruses predominantly replicated in the brains of birds that died of infection. Seroconversion was observed in most surviving birds, except some black-crowned night herons. These results demonstrate that most Ardeidae species are susceptible to H5 HPAIVs, sometimes with lethal effects. Herons are mostly colonial and often share habitats with Anseriformes, natural hosts of influenza A viruses; therefore, the risks of cluster infection and contribution to viral dissemination should be continuously evaluated. RESEARCH HIGHLIGHTSClade 2.3.2.1 H5N1 HPAIV causes lethal infections in Ardeidae sp.Viruses are transmitted among grey herons.Some herons with HPAIV showed conjunctivitis or neurological symptoms.HPAIV systemically replicated in herons tissues.
  • Mapping of Antibody Epitopes on the Crimean-Congo Hemorrhagic Fever Virus Nucleoprotein.
    Boniface Pongombo Lombe; Takeshi Saito; Hiroko Miyamoto; Akina Mori-Kajihara; Masahiro Kajihara; Masayuki Saijo; Justin Masumu; Takanari Hattori; Manabu Igarashi; Ayato Takada
    Viruses, 14, 3, 06 Mar. 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Crimean-Congo hemorrhagic fever virus (CCHFV), a nairovirus, is a tick-borne zoonotic virus that causes hemorrhagic fever in humans. The CCHFV nucleoprotein (NP) is the antigen most used for serological screening of CCHFV infection in animals and humans. To gain insights into antibody epitopes on the NP molecule, we produced recombinant chimeric NPs between CCHFV and Nairobi sheep disease virus (NSDV), which is another nairovirus, and tested rabbit and mouse antisera/immune ascites, anti-NP monoclonal antibodies, and CCHFV-infected animal/human sera for their reactivities to the NP antigens. We found that the amino acids at positions 161-320 might include dominant epitopes recognized by anti-CCHFV IgG antibodies, whereas cross-reactivity between anti-CCHFV and anti-NSDV antibodies was limited. Their binding capacities were further tested using a series of synthetic peptides whose sequences were derived from CCHFV NP. IgG antibodies in CCHFV-infected monkeys and patients were reactive to some of the synthetic peptide antigens (e.g., amino acid residues at positions 131-150 and 211-230). Only a few peptides were recognized by IgG antibodies in the anti-NSDV serum. These results provide useful information to improve NP-based antibody detection assays as well as antigen detection tests relying on anti-NP monoclonal antibodies.
  • Molecular Mechanisms Underlying the Cellular Entry and Host Range Restriction of Lujo Virus.
    Takeshi Saito; Takanari Hattori; Kosuke Okuya; Rashid Manzoor; Hiroko Miyamoto; Masahiro Kajihara; Ayato Takada
    mBio, 13, 1, e0306021, 15 Feb. 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Like other human-pathogenic arenaviruses, Lujo virus (LUJV) is a causative agent of viral hemorrhagic fever in humans. LUJV infects humans with high mortality rates, but the susceptibilities of other animal species and the molecular determinants of its host specificity remain unknown. We found that mouse- and hamster-derived cell lines (NIH 3T3 and BHK, respectively) were less susceptible to a replication-incompetent recombinant vesicular stomatitis virus (Indiana) pseudotyped with the LUJV glycoprotein (GP) (VSVΔG*-LUJV/GP) than were human-derived cell lines (HEK293T and Huh7). To determine the cellular factors involved in the differential susceptibilities between the human and mouse cell lines, we focused on the CD63 molecule, which is required for pH-activated GP-mediated membrane fusion during LUJV entry into host cells. The exogenous introduction of human CD63, but not mouse or hamster CD63, into BHK cells significantly increased susceptibility to VSVΔG*-LUJV/GP. Using chimeric human-mouse CD63 proteins, we found that the amino acid residues at positions 141 to 150 in the large extracellular loop (LEL) region of CD63 were important for the cellular entry of VSVΔG*-LUJV/GP. By site-directed mutagenesis, we further determined that a phenylalanine at position 143 in human CD63 was the key residue for efficient membrane fusion and VSVΔG*-LUJV/GP infection. Our data suggest that the interaction of LUJV GP with the LEL region of CD63 is essential for cell susceptibility to LUJV, thus providing new insights into the molecular mechanisms underlying the cellular entry of LUJV and the host range restriction of this virus. IMPORTANCE Lujo virus (LUJV) infects humans with high mortality rates, but the host range of LUJV remains unknown. We found that rodent-derived cell lines were less susceptible to LUJV infection than were human-derived cell lines, and the differential susceptibilities were determined by the difference of CD63, the intercellular receptor of LUJV. We further identified an amino acid residue on human CD63 important for efficient LUJV infection. These results suggest that the interaction between LUJV glycoprotein and CD63 is one of the important factors determining the host range of LUJV. Our findings on the CD63-regulated susceptibilities of the cell lines to LUJV infection provide important information for the development of anti-LUJV drugs as well as the identification of natural hosts of LUJV. Importantly, our data support a concept explaining the molecular mechanism underlying viral tropisms controlled by endosomal receptors.
  • Current knowledge of vector-borne zoonotic pathogens in Zambia: A clarion call to scaling-up "One Health" research in the wake of emerging and re-emerging infectious diseases.
    Benjamin Mubemba; Monicah M Mburu; Katendi Changula; Walter Muleya; Lavel C Moonga; Herman M Chambaro; Masahiro Kajihara; Yongjin Qiu; Yasuko Orba; Kyoko Hayashida; Catherine G Sutcliffe; Douglas E Norris; Philip E Thuma; Phillimon Ndubani; Simbarashe Chitanga; Hirofumi Sawa; Ayato Takada; Edgar Simulundu
    PLoS neglected tropical diseases, 16, 2, e0010193, Feb. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Although vector-borne zoonotic diseases are a major public health threat globally, they are usually neglected, especially among resource-constrained countries, including those in sub-Saharan Africa. This scoping review examined the current knowledge and identified research gaps of vector-borne zoonotic pathogens in Zambia. METHODS AND FINDINGS: Major scientific databases (Web of Science, PubMed, Scopus, Google Scholar, CABI, Scientific Information Database (SID)) were searched for articles describing vector-borne (mosquitoes, ticks, fleas and tsetse flies) zoonotic pathogens in Zambia. Several mosquito-borne arboviruses have been reported including Yellow fever, Ntaya, Mayaro, Dengue, Zika, West Nile, Chikungunya, Sindbis, and Rift Valley fever viruses. Flea-borne zoonotic pathogens reported include Yersinia pestis and Rickettsia felis. Trypanosoma sp. was the only tsetse fly-borne pathogen identified. Further, tick-borne zoonotic pathogens reported included Crimean-Congo Haemorrhagic fever virus, Rickettsia sp., Anaplasma sp., Ehrlichia sp., Borrelia sp., and Coxiella burnetii. CONCLUSIONS: This study revealed the presence of many vector-borne zoonotic pathogens circulating in vectors and animals in Zambia. Though reports of human clinical cases were limited, several serological studies provided considerable evidence of zoonotic transmission of vector-borne pathogens in humans. However, the disease burden in humans attributable to vector-borne zoonotic infections could not be ascertained from the available reports and this precludes the formulation of national policies that could help in the control and mitigation of the impact of these diseases in Zambia. Therefore, there is an urgent need to scale-up "One Health" research in emerging and re-emerging infectious diseases to enable the country to prepare for future epidemics, including pandemics.
  • Seroprevalence and Risk Factors of Crimean-Congo Hemorrhagic Fever in Cattle of Smallholder Farmers in Central Malawi.
    Marvin Collen Phonera; Martin Chitolongo Simuunza; Henson Kainga; Joseph Ndebe; Mwelwa Chembensofu; Elisha Chatanga; Setiala Kanyanda; Katendi Changula; Walter Muleya; Benjamin Mubemba; Simbarashe Chitanga; Masahiro Kajihara; Hirofumi Sawa; Gilson Njunga; Ayato Takada; Edgar Simulundu
    Pathogens (Basel, Switzerland), 10, 12, 10 Dec. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in Africa, Asia, and Eastern Europe where it circulates among animals and ticks causing sporadic outbreaks in humans. Although CCHF is endemic in sub-Saharan Africa, epidemiological information is lacking in many countries, including Malawi. To assess the risk of CCHF in Malawi, we conducted an epidemiological study in cattle reared by smallholder livestock farmers in central Malawi. A cross-sectional study was conducted in April 2020 involving seven districts, four from Kasungu and three from Lilongwe Agriculture Development Divisions. A structured questionnaire was administered to farmers to obtain demographic, animal management, and ecological risk factors data. Sera were collected from randomly selected cattle and screened for CCHF virus (CCHFV) specific antibodies using a commercial ELISA kit. Ticks were collected from cattle and classified morphologically to species level. An overall CCHFV seropositivity rate of 46.9% (n = 416; 95% CI: 42.0-51.8%) was observed. The seropositivity was significantly associated with the age of cattle (p < 0.001), sex (p < 0.001), presence of ticks in herds (p = 0.01), district (p = 0.025), and type of grazing lands (p = 0.013). Five species of ticks were identified, including Hyalomma truncatum, a known vector of CCHFV. Ticks of the species Hyalomma truncatum were not detected in two districts with the highest seroprevalence for CCHF and vector competency must be further explored in the study area. To our knowledge, this is the first report of serologic evidence of the presence of CCHV among smallholder cattle in central Malawi. This study emphasizes the need for continued monitoring of CCHFV infection among livestock, ticks, and humans for the development of data-based risk mitigation strategies.
  • Structural Requirements in the Hemagglutinin Cleavage Site-Coding RNA Region for the Generation of Highly Pathogenic Avian Influenza Virus.
    Yurie Kida; Kosuke Okuya; Takeshi Saito; Junya Yamagishi; Aiko Ohnuma; Takanari Hattori; Hiroko Miyamoto; Rashid Manzoor; Reiko Yoshida; Naganori Nao; Masahiro Kajihara; Tokiko Watanabe; Ayato Takada
    Pathogens (Basel, Switzerland), 10, 12, 09 Dec. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Highly pathogenic avian influenza viruses (HPAIVs) with H5 and H7 hemagglutinin (HA) subtypes are derived from their low pathogenic counterparts following the acquisition of multiple basic amino acids in their HA cleavage site. It has been suggested that consecutive adenine residues and a stem-loop structure in the viral RNA region that encodes the cleavage site are essential for the acquisition of the polybasic cleavage site. By using a reporter assay to detect non-templated nucleotide insertions, we found that insertions more frequently occurred in the RNA region (29 nucleotide-length) encoding the cleavage site of an H5 HA gene that was predicted to have a stem-loop structure containing consecutive adenines than in a mutated corresponding RNA region that had a disrupted loop structure with fewer adenines. In virus particles generated by using reverse genetics, nucleotide insertions that created additional codons for basic amino acids were found in the RNA region encoding the cleavage site of an H5 HA gene but not in the mutated RNA region. We confirmed the presence of virus clones with the ability to replicate without trypsin in a plaque assay and to cause lethal infection in chicks. These results demonstrate that the stem-loop structure containing consecutive adenines in HA genes is a key molecular determinant for the emergence of H5 HPAIVs.
  • Influenza A and D Viruses in Non-Human Mammalian Hosts in Africa: A Systematic Review and Meta-Analysis.
    Annie Kalonda; Marvin Phonera; Ngonda Saasa; Masahiro Kajihara; Catherine G Sutcliffe; Hirofumi Sawa; Ayato Takada; Edgar Simulundu
    Viruses, 13, 12, 02 Dec. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, We conducted a systematic review and meta-analysis to investigate the prevalence and current knowledge of influenza A virus (IAV) and influenza D virus (IDV) in non-human mammalian hosts in Africa. PubMed, Google Scholar, Wiley Online Library and World Organisation for Animal Health (OIE-WAHIS) were searched for studies on IAV and IDV from 2000 to 2020. Pooled prevalence and seroprevalences were estimated using the quality effects meta-analysis model. The estimated pooled prevalence and seroprevalence of IAV in pigs in Africa was 1.6% (95% CI: 0-5%) and 14.9% (95% CI: 5-28%), respectively. The seroprevalence of IDV was 87.2% (95% CI: 24-100%) in camels, 9.3% (95% CI: 0-24%) in cattle, 2.2% (95% CI: 0-4%) in small ruminants and 0.0% (95% CI: 0-2%) in pigs. In pigs, H1N1 and H1N1pdm09 IAVs were commonly detected. Notably, the highly pathogenic H5N1 virus was also detected in pigs. Other subtypes detected serologically and/or virologically included H3N8 and H7N7 in equids, H1N1, and H3N8 and H5N1 in dogs and cats. Furthermore, various wildlife animals were exposed to different IAV subtypes. For prudent mitigation of influenza epizootics and possible human infections, influenza surveillance efforts in Africa should not neglect non-human mammalian hosts. The impact of IAV and IDV in non-human mammalian hosts in Africa deserves further investigation.
  • Correction to: 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.
    Jens H Kuhn; Scott Adkins; Bernard R Agwanda; Rim Al Kubrusli; Sergey V Alkhovsky; Gaya K Amarasinghe; Tatjana Avšič-Županc; María A Ayllón; Justin Bahl; Anne Balkema-Buschmann; Matthew J Ballinger; Christopher F Basler; Sina Bavari; Martin Beer; Nicolas Bejerman; Andrew J Bennett; Dennis A Bente; Éric Bergeron; Brian H Bird; Carol D Blair; Kim R Blasdell; Dag-Ragnar Blystad; Jamie Bojko; Wayne B Borth; Steven Bradfute; Rachel Breyta; Thomas Briese; Paul A Brown; Judith K Brown; Ursula J Buchholz; Michael J Buchmeier; Alexander Bukreyev; Felicity Burt; Carmen Büttner; Charles H Calisher; Mengji Cao; Inmaculada Casas; Kartik Chandran; Rémi N Charrel; Qi Cheng; Yuya Chiaki; Marco Chiapello; Il-Ryong Choi; Marina Ciuffo; J Christopher S Clegg; Ian Crozier; Elena Dal Bó; Juan Carlos de la Torre; Xavier de Lamballerie; Rik L de Swart; Humberto Debat; Nolwenn M Dheilly; Emiliano Di Cicco; Nicholas Di Paola; Francesco Di Serio; Ralf G Dietzgen; Michele Digiaro; Olga Dolnik; Michael A Drebot; J Felix Drexler; William G Dundon; W Paul Duprex; Ralf Dürrwald; John M Dye; Andrew J Easton; Hideki Ebihara; Toufic Elbeaino; Koray Ergünay; Hugh W Ferguson; Anthony R Fooks; Marco Forgia; Pierre B H Formenty; Jana Fránová; Juliana Freitas-Astúa; Jingjing Fu; Stephanie Fürl; Selma Gago-Zachert; George Fú Gāo; María Laura García; Adolfo García-Sastre; Aura R Garrison; Thomas Gaskin; Jean-Paul J Gonzalez; Anthony Griffiths; Tony L Goldberg; Martin H Groschup; Stephan Günther; Roy A Hall; John Hammond; Tong Han; Jussi Hepojoki; Roger Hewson; Jiang Hong; Ni Hong; Seiji Hongo; Masayuki Horie; John S Hu; Tao Hu; Holly R Hughes; Florian Hüttner; Timothy H Hyndman; M Ilyas; Risto Jalkanen; Dàohóng Jiāng; Gilda B Jonson; Sandra Junglen; Fujio Kadono; Karia H Kaukinen; Michael Kawate; Boris Klempa; Jonas Klingström; Gary Kobinger; Igor Koloniuk; Hideki Kondō; Eugene V Koonin; Mart Krupovic; Kenji Kubota; Gael Kurath; Lies Laenen; Amy J Lambert; Stanley L Langevin; Benhur Lee; Elliot J Lefkowitz; Eric M Leroy; Shaorong Li; Longhui Li; Jiànróng Lǐ; Huazhen Liu; Igor S Lukashevich; Piet Maes; William Marciel de Souza; Marco Marklewitz; Sergio H Marshall; Shin-Yi L Marzano; Sebastien Massart; John W McCauley; Michael Melzer; Nicole Mielke-Ehret; Kristina M Miller; Tobi J Ming; Ali Mirazimi; Gideon J Mordecai; Hans-Peter Mühlbach; Elke Mühlberger; Rayapati Naidu; Tomohide Natsuaki; José A Navarro; Sergey V Netesov; Gabriele Neumann; Norbert Nowotny; Márcio R T Nunes; Alejandro Olmedo-Velarde; Gustavo Palacios; Vicente Pallás; Bernadett Pályi; Anna Papa; Sofia Paraskevopoulou; Adam C Park; Colin R Parrish; David A Patterson; Alex Pauvolid-Corrêa; Janusz T Pawęska; Susan Payne; Carlotta Peracchio; Daniel R Pérez; Thomas S Postler; Liying Qi; Sheli R Radoshitzky; Renato O Resende; Carina A Reyes; Bertus K Rima; Gabriel Robles Luna; Víctor Romanowski; Paul Rota; Dennis Rubbenstroth; Luisa Rubino; Jonathan A Runstadler; Sead Sabanadzovic; Amadou Alpha Sall; Maria S Salvato; Rosemary Sang; Takahide Sasaya; Angela D Schulze; Martin Schwemmle; Mang Shi; Xiǎohóng Shí; Zhènglì Shí; Yoshifumi Shimomoto; Yukio Shirako; Stuart G Siddell; Peter Simmonds; Manuela Sironi; Guy Smagghe; Sophie Smither; Jin-Won Song; Kirsten Spann; Jessica R Spengler; Mark D Stenglein; David M Stone; Jari Sugano; Curtis A Suttle; Amy Tabata; Ayato Takada; Shigeharu Takeuchi; David P Tchouassi; Amy Teffer; Robert B Tesh; Natalie J Thornburg; Yasuhiro Tomitaka; Keizō Tomonaga; Noël Tordo; Baldwyn Torto; Jonathan S Towner; Shinya Tsuda; Changchun Tu; Massimo Turina; Ioannis E Tzanetakis; Janice Uchida; Tomio Usugi; Anna Maria Vaira; Marta Vallino; Bernadette van den Hoogen; Arvind Varsani; Nikos Vasilakis; Martin Verbeek; Susanne von Bargen; Jiro Wada; Victoria Wahl; Peter J Walker; Lin-Fa Wang; Guoping Wang; Yanxiang Wang; Yaqin Wang; Muhammad Waqas; Tàiyún Wèi; Shaohua Wen; Anna E Whitfield; John V Williams; Yuri I Wolf; Jiangxiang Wu; Lei Xu; Hironobu Yanagisawa; Caixia Yang; Zuokun Yang; F Murilo Zerbini; Lifeng Zhai; Yong-Zhen Zhang; Song Zhang; Jinguo Zhang; Zhe Zhang; Xueping Zhou
    Archives of virology, 166, 12, 3567, 3579, Dec. 2021, [Peer-reviewed], [International Magazine]
    English
  • Functional Importance of Hydrophobic Patches on the Ebola Virus VP35 IFN-Inhibitory Domain.
    Nodoka Kasajima; Keita Matsuno; Hiroko Miyamoto; Masahiro Kajihara; Manabu Igarashi; Ayato Takada
    Viruses, 13, 11, 20 Nov. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Viral protein 35 (VP35) of Ebola virus (EBOV) is a multifunctional protein that mainly acts as a viral polymerase cofactor and an interferon antagonist. VP35 interacts with the viral nucleoprotein (NP) and double-stranded RNA for viral RNA transcription/replication and inhibition of type I interferon (IFN) production, respectively. The C-terminal portion of VP35, which is termed the IFN-inhibitory domain (IID), is important for both functions. To further identify critical regions in this domain, we analyzed the physical properties of the surface of VP35 IID, focusing on hydrophobic patches, which are expected to be functional sites that are involved in interactions with other molecules. Based on the known structural information of VP35 IID, three hydrophobic patches were identified on its surface and their biological importance was investigated using minigenome and IFN-β promoter-reporter assays. Site-directed mutagenesis revealed that some of the amino acid substitutions that were predicted to disrupt the hydrophobicity of the patches significantly decreased the efficiency of viral genome replication/transcription due to reduced interaction with NP, suggesting that the hydrophobic patches might be critical for the formation of a replication complex through the interaction with NP. It was also found that the hydrophobic patches were involved in the IFN-inhibitory function of VP35. These results highlight the importance of hydrophobic patches on the surface of EBOV VP35 IID and also indicate that patch analysis is useful for the identification of amino acid residues that directly contribute to protein functions.
  • Serological and molecular epidemiological study on swine influenza in Zambia.
    Hayato Harima; Kosuke Okuya; Masahiro Kajihara; Hirohito Ogawa; Edgar Simulundu; Eugene Bwalya; Yongjin Qiu; Akina Mori-Kajihara; Musso Munyeme; Yoshihiro Sakoda; Takehiko Saito; Bernard M Hang'ombe; Hirofumi Sawa; Aaron S Mweene; Ayato Takada
    Transboundary and emerging diseases, 69, 4, e931-e943, 01 Nov. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Influenza A viruses (IAVs) cause highly contagious respiratory diseases in humans and animals. In 2009, a swine-origin pandemic H1N1 IAV, designated A(H1N1)pdm09 virus, spread worldwide, and has since frequently been introduced into pig populations. Since novel reassortant IAVs with pandemic potential may emerge in pigs, surveillance for IAV in pigs is therefore necessary not only for the pig industry but also for public health. However, epidemiological information on IAV infection of pigs in Africa remains sparse. In this study, we collected 246 serum and 605 nasal swab samples from pigs in Zambia during the years 2011-2018. Serological analyses revealed that 49% and 32% of the sera collected in 2011 were positive for hemagglutination-inhibition (HI) and neutralizing antibodies against A(H1N1)pdm09 virus, respectively, whereas less than 5.3% of sera collected during the following period (2012-2018) were positive in both serological tests. The positive rate and the neutralization titres to A(H1N1)pdm09 virus were higher than those to classical swine H1N1 and H1N2 IAVs. On the other hand, the positive rate for swine H3N2 IAV was very low in the pig population in Zambia in 2011-2018 (5.3% and 0% in HI and neutralization tests, respectively). From nasal swab samples, we isolated one H3N2 and eight H1N1 IAV strains with an isolation rate of 1.5%. Phylogenetic analyses of all eight gene segments revealed that the isolated IAVs were closely related to human IAV strains belonging to A(H1N1)pdm09 and seasonal H3N2 lineages. Our findings indicate that reverse zoonotic transmission from humans to pigs occurred during the study period in Zambia and highlight the need for continued surveillance to monitor the status of IAVs circulating in swine populations in Africa.
  • 北海道の野鳥から検出されたロタウイルスA JC-105株の遺伝学的解析
    藤井 祐至; 正谷 達謄; 西山 祥子; 藤原 拓朗; 迫田 義博; 高田 礼人; 小澤 真; 杉山 誠; 伊藤 直人
    日本獣医学会学術集会講演要旨集, 164回, [FO, 1], (公社)日本獣医学会, Sep. 2021
    Japanese
  • Attenuated infection by a Pteropine orthoreovirus isolated from an Egyptian fruit bat in Zambia.
    Hayato Harima; Michihito Sasaki; Yasuko Orba; Kosuke Okuya; Yongjin Qiu; Christida E Wastika; Katendi Changula; Masahiro Kajihara; Edgar Simulundu; Tomoyuki Yamaguchi; Yoshiki Eto; Akina Mori-Kajihara; Akihiko Sato; Satoshi Taniguchi; Ayato Takada; Masayuki Saijo; Bernard M Hang'ombe; Hirofumi Sawa
    PLoS neglected tropical diseases, 15, 9, e0009768, Sep. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Pteropine orthoreovirus (PRV) is an emerging bat-borne zoonotic virus that causes severe respiratory illness in humans. Although PRVs have been identified in fruit bats and humans in Australia and Asia, little is known about the prevalence of PRV infection in Africa. Therefore, this study performed an PRV surveillance in fruit bats in Zambia. METHODS: Egyptian fruit bats (Rousettus aegyptiacus, n = 47) and straw-colored fruit bats (Eidolon helvum, n = 33) captured in Zambia in 2017-2018 were screened for PRV infection using RT-PCR and serum neutralization tests. The complete genome sequence of an isolated PRV strain was determined by next generation sequencing and subjected to BLAST and phylogenetic analyses. Replication capacity and pathogenicity of the strain were investigated using Vero E6 cell cultures and BALB/c mice, respectively. RESULTS: An PRV strain, tentatively named Nachunsulwe-57, was isolated from one Egyptian fruit bat. Serological assays demonstrated that 98% of sera (69/70) collected from Egyptian fruit bats (n = 37) and straw-colored fruit bats (n = 33) had neutralizing antibodies against PRV. Genetic analyses revealed that all 10 genome segments of Nachunsulwe-57 were closely related to a bat-derived Kasama strain found in Uganda. Nachunsulwe-57 showed less efficiency in viral growth and lower pathogenicity in mice than another PRV strain, Miyazaki-Bali/2007, isolated from a patient. CONCLUSIONS: A high proportion of Egyptian fruit bats and straw-colored fruit bats were found to be seropositive to PRV in Zambia. Importantly, a new PRV strain (Nachunsulwe-57) was isolated from an Egyptian fruit bat in Zambia, which had relatively weak pathogenicity in mice. Taken together, our findings provide new epidemiological insights about PRV infection in bats and indicate the first isolation of an PRV strain that may have low pathogenicity to humans.
  • 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.
    Jens H Kuhn; Scott Adkins; Bernard R Agwanda; Rim Al Kubrusli; Sergey V Alkhovsky Aльxoвcкий Cepгeй Bлaдимиpoвич; Gaya K Amarasinghe; Tatjana Avšič-Županc; María A Ayllón; Justin Bahl; Anne Balkema-Buschmann; Matthew J Ballinger; Christopher F Basler; Sina Bavari; Martin Beer; Nicolas Bejerman; Andrew J Bennett; Dennis A Bente; Éric Bergeron; Brian H Bird; Carol D Blair; Kim R Blasdell; Dag-Ragnar Blystad; Jamie Bojko; Wayne B Borth; Steven Bradfute; Rachel Breyta; Thomas Briese; Paul A Brown; Judith K Brown; Ursula J Buchholz; Michael J Buchmeier; Alexander Bukreyev; Felicity Burt; Carmen Büttner; Charles H Calisher; Mengji Cao 曹孟籍; Inmaculada Casas; Kartik Chandran; Rémi N Charrel; Qi Cheng; Yuya Chiaki 千秋祐也; Marco Chiapello; Il-Ryong Choi; Marina Ciuffo; J Christopher S Clegg; Ian Crozier; Elena Dal Bó; Juan Carlos de la Torre; Xavier de Lamballerie; Rik L de Swart; Humberto Debat; Nolwenn M Dheilly; Emiliano Di Cicco; Nicholas Di Paola; Francesco Di Serio; Ralf G Dietzgen; Michele Digiaro; Olga Dolnik; Michael A Drebot; J Felix Drexler; William G Dundon; W Paul Duprex; Ralf Dürrwald; John M Dye; Andrew J Easton; Hideki Ebihara 海老原秀喜; Toufic Elbeaino; Koray Ergünay; Hugh W Ferguson; Anthony R Fooks; Marco Forgia; Pierre B H Formenty; Jana Fránová; Juliana Freitas-Astúa; Jingjing Fu 付晶晶; Stephanie Fürl; Selma Gago-Zachert; George Fú Gāo 高福; María Laura García; Adolfo García-Sastre; Aura R Garrison; Thomas Gaskin; Jean-Paul J Gonzalez; Anthony Griffiths; Tony L Goldberg; Martin H Groschup; Stephan Günther; Roy A Hall; John Hammond; Tong Han 韩彤; Jussi Hepojoki; Roger Hewson; Jiang Hong 洪健; Ni Hong 洪霓; Seiji Hongo 本郷誠治; Masayuki Horie 堀江真行; John S Hu; Tao Hu; Holly R Hughes; Florian Hüttner; Timothy H Hyndman; M Ilyas; Risto Jalkanen; Dàohóng Jiāng 姜道宏; Gilda B Jonson; Sandra Junglen; Fujio Kadono 上遠野冨士夫; Karia H Kaukinen; Michael Kawate; Boris Klempa; Jonas Klingström; Gary Kobinger; Igor Koloniuk; Hideki Kondō 近藤秀樹; Eugene V Koonin; Mart Krupovic; Kenji Kubota 久保田健嗣; Gael Kurath; Lies Laenen; Amy J Lambert; Stanley L Langevin; Benhur Lee; Elliot J Lefkowitz; Eric M Leroy; Shaorong Li 李邵蓉; Longhui Li 李龙辉; Jiànróng Lǐ 李建荣; Huazhen Liu 刘华珍; Igor S Lukashevich; Piet Maes; William Marciel de Souza; Marco Marklewitz; Sergio H Marshall; Shin-Yi L Marzano; Sebastien Massart; John W McCauley; Michael Melzer; Nicole Mielke-Ehret; Kristina M Miller; Tobi J Ming; Ali Mirazimi; Gideon J Mordecai; Hans-Peter Mühlbach; Elke Mühlberger; Rayapati Naidu; Tomohide Natsuaki 夏秋知英; José A Navarro; Sergey V Netesov Heтёcoв Cepгeй Bиктopoвич; Gabriele Neumann; Norbert Nowotny; Márcio R T Nunes; Alejandro Olmedo-Velarde; Gustavo Palacios; Vicente Pallás; Bernadett Pályi; Anna Papa Άννα Παπά; Sofia Paraskevopoulou Σοφία Παρασκευοπούλου; Adam C Park; Colin R Parrish; David A Patterson; Alex Pauvolid-Corrêa; Janusz T Pawęska; Susan Payne; Carlotta Peracchio; Daniel R Pérez; Thomas S Postler; Liying Qi 亓立莹; Sheli R Radoshitzky; Renato O Resende; Carina A Reyes; Bertus K Rima; Gabriel Robles Luna; Víctor Romanowski; Paul Rota; Dennis Rubbenstroth; Luisa Rubino; Jonathan A Runstadler; Sead Sabanadzovic; Amadou Alpha Sall; Maria S Salvato; Rosemary Sang; Takahide Sasaya 笹谷孝英; Angela D Schulze; Martin Schwemmle; Mang Shi 施莽; Xiǎohóng Shí 石晓宏; Zhènglì Shí 石正丽; Yoshifumi Shimomoto 下元祥史; Yukio Shirako; Stuart G Siddell; Peter Simmonds; Manuela Sironi; Guy Smagghe; Sophie Smither; Jin-Won Song 송진원; Kirsten Spann; Jessica R Spengler; Mark D Stenglein; David M Stone; Jari Sugano; Curtis A Suttle; Amy Tabata; Ayato Takada 高田礼人; Shigeharu Takeuchi 竹内繁治; David P Tchouassi; Amy Teffer; Robert B Tesh; Natalie J Thornburg; Yasuhiro Tomitaka 冨高保弘; Keizō Tomonaga 朝長啓造; Noël Tordo; Baldwyn Torto; Jonathan S Towner; Shinya Tsuda 津田新哉; Changchun Tu 涂长春; Massimo Turina; Ioannis E Tzanetakis; Janice Uchida; Tomio Usugi 宇杉富雄; Anna Maria Vaira; Marta Vallino; Bernadette van den Hoogen; Arvind Varsani; Nikos Vasilakis Νίκος Βασιλάκης; Martin Verbeek; Susanne von Bargen; Jiro Wada 和田治郎; Victoria Wahl; Peter J Walker; Lin-Fa Wang 王林发; Guoping Wang 王国平; Yanxiang Wang 王雁翔; Yaqin Wang 王亚琴; Muhammad Waqas; Tàiyún Wèi 魏太云; Shaohua Wen 温少华; Anna E Whitfield; John V Williams; Yuri I Wolf; Jiangxiang Wu 吴建祥; Lei Xu 徐雷; Hironobu Yanagisawa 栁澤広宣; Caixia Yang 杨彩霞; Zuokun Yang 杨作坤; F Murilo Zerbini; Lifeng Zhai 翟立峰; Yong-Zhen Zhang 张永振; Song Zhang 张松; Jinguo Zhang 张靖国; Zhe Zhang 张哲; Xueping Zhou 周雪平
    Archives of virology, 166, 12, 3513, 3566, 31 Aug. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
  • Dual Effect of Organogermanium Compound THGP on RIG-I-Mediated Viral Sensing and Viral Replication during Influenza a Virus Infection.
    Sunanda Baidya; Yoko Nishimoto; Seiichi Sato; Yasuhiro Shimada; Nozomi Sakurai; Hirotaka Nonaka; Koki Noguchi; Mizuki Kido; Satoshi Tadano; Kozo Ishikawa; Kai Li; Aoi Okubo; Taisho Yamada; Yasuko Orba; Michihito Sasaki; Hirofumi Sawa; Hiroko Miyamoto; Ayato Takada; Takashi Nakamura; Akinori Takaoka
    Viruses, 13, 9, 24 Aug. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The interaction of viral nucleic acid with protein factors is a crucial process for initiating viral polymerase-mediated viral genome replication while activating pattern recognition receptor (PRR)-mediated innate immune responses. It has previously been reported that a hydrolysate of Ge-132, 3-(trihydroxygermyl) propanoic acid (THGP), shows a modulatory effect on microbial infections, inflammation, and immune responses. However, the detailed mechanism by which THGP can modify these processes during viral infections remained unknown. Here, we show that THGP can specifically downregulate type I interferon (IFN) production in response to stimulation with a cytosolic RNA sensor RIG-I ligand 5'-triphosphate RNA (3pRNA) but not double-stranded RNA, DNA, or lipopolysaccharide. Consistently, treatment with THGP resulted in the dose-dependent suppression of type I IFN induction upon infections with influenza virus (IAV) and vesicular stomatitis virus, which are known to be mainly sensed by RIG-I. Mechanistically, THGP directly binds to the 5'-triphosphate moiety of viral RNA and competes with RIG-I-mediated recognition. Furthermore, we found that THGP can directly counteract the replication of IAV but not EMCV (encephalitismyocarditis virus), by inhibiting the interaction of viral polymerase with RNA genome. Finally, IAV RNA levels were significantly reduced in the lung tissues of THGP-treated mice when compared with untreated mice. These results suggest a possible therapeutic implication of THGP and show direct antiviral action, together with the suppressive activity of innate inflammation.
  • Mosquito-Borne Viral Pathogens Detected in Zambia: A Systematic Review.
    Rachel Milomba Velu; Geoffrey Kwenda; Liyali Libonda; Caroline Cleopatra Chisenga; Bumbangi Nsoni Flavien; Obvious Nchimunya Chilyabanyama; Michelo Simunyandi; Samuel Bosomprah; Nicholus Chintu Sande; Katendi Changula; Walter Muleya; Monicah Mirai Mburu; Benjamin Mubemba; Simbarashe Chitanga; John Tembo; Matthew Bates; Nathan Kapata; Yasuko Orba; Masahiro Kajihara; Ayato Takada; Hirofumi Sawa; Roma Chilengi; Edgar Simulundu
    Pathogens (Basel, Switzerland), 10, 8, 10 Aug. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Emerging and re-emerging mosquito-borne viral diseases are a threat to global health. This systematic review aimed to investigate the available evidence of mosquito-borne viral pathogens reported in Zambia. A search of literature was conducted in PubMed and Google Scholar for articles published from 1 January 1930 to 30 June 2020 using a combination of keywords. Eight mosquito-borne viruses belonging to three families, Togaviridae, Flaviviridae and Phenuiviridae were reported. Three viruses (Chikungunya virus, Mayaro virus, Mwinilunga virus) were reported among the togaviruses whilst four (dengue virus, West Nile virus, yellow fever virus, Zika virus) were among the flavivirus and only one virus, Rift Valley fever virus, was reported in the Phenuiviridae family. The majority of these mosquito-borne viruses were reported in Western and North-Western provinces. Aedes and Culex species were the main mosquito-borne viral vectors reported. Farming, fishing, movement of people and rain patterns were among factors associated with mosquito-borne viral infection in Zambia. Better diagnostic methods, such as the use of molecular tools, to detect the viruses in potential vectors, humans, and animals, including the recognition of arboviral risk zones and how the viruses circulate, are important for improved surveillance and design of effective prevention and control measures.
  • Screening of tick-borne pathogens in argasid ticks in Zambia: Expansion of the geographic distribution of Rickettsia lusitaniae and Rickettsia hoogstraalii and detection of putative novel Anaplasma species.
    Yongjin Qiu; Martin Simuunza; Masahiro Kajihara; Herman Chambaro; Hayato Harima; Yoshiki Eto; Edgar Simulundu; David Squarre; Shiho Torii; Ayato Takada; Bernard Mudenda Hang'ombe; Hirofumi Sawa; Chihiro Sugimoto; Ryo Nakao
    Ticks and tick-borne diseases, 12, 4, 101720, 101720, Jul. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Ticks (Ixodidae and Argasidae) are important arthropod vectors of various pathogens that cause human and animal infectious diseases. Many previously published studies on tick-borne pathogens focused on those transmitted by ixodid ticks. Although there are increasing reports of viral pathogens associated with argasid ticks, information on bacterial pathogens they transmit is scarce. The aim of this molecular study was to detect and characterize Rickettsia and Anaplasmataceae in three different argasid tick species, Ornithodoros faini, Ornithodoros moubata, and Argas walkerae collected in Zambia. Rickettsia hoogstraalii and Rickettsia lusitaniae were detected in 77 % (77/100) of Ar. walkerae and 10 % (5/50) of O. faini, respectively. All O. moubata pool samples (n = 124) were negative for rickettsial infections. Anaplasmataceae were detected in 63 % (63/100) of Ar. walkerae and in 82.2 % (102/124) of O. moubata pools, but not in O. faini. Phylogenetic analysis based on the concatenated sequences of 16S rRNA and groEL genes revealed that Anaplasma spp. detected in the present study were distinct from previously validated Anaplasma species, indicating that the current knowledge on the diversity and vector range of Anaplasma spp. is incomplete. Our findings highlight new geographical records of R. lusitaniae and R. hoogstraalii and confirm that the wide geographic distribution of these species includes the African continent. The data presented here increase our knowledge on argasid tick-borne bacteria and contribute toward understanding their epidemiology.
  • Serological Evidence of Filovirus Infection in Nonhuman Primates in Zambia.
    Katendi Changula; Edgar Simulundu; Boniface Pongombo Lombe; Eri Nakayama; Hiroko Miyamoto; Yuji Takahashi; Hirofumi Sawa; Chuma Simukonda; Bernard M Hang'ombe; Ayato Takada
    Viruses, 13, 7, 30 Jun. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Ebolaviruses and marburgviruses are filoviruses that are known to cause severe hemorrhagic fever in humans and nonhuman primates (NHPs). While some bat species are suspected to be natural reservoirs of these filoviruses, wild NHPs often act as intermediate hosts for viral transmission to humans. Using an enzyme-linked immunosorbent assay, we screened two NHP species, wild baboons and vervet monkeys captured in Zambia, for their serum IgG antibodies specific to the envelope glycoproteins of filoviruses. From 243 samples tested, 39 NHPs (16%) were found to be seropositive either for ebolaviruses or marburgviruses with endpoint antibody titers ranging from 100 to 25,600. Interestingly, antibodies reactive to Reston virus, which is found only in Asia, were detected in both NHP species. There was a significant difference in the seropositivity for the marburgvirus antigen between the two NHP species, with baboons having a higher positive rate. These results suggest that wild NHPs in Zambia might be nonlethally exposed to these filoviruses, and this emphasizes the need for continuous monitoring of filovirus infection in wild animals to better understand the ecology of filoviruses and to assess potential risks of outbreaks in humans in previously nonendemic countries.
  • Molecular Detection and Genotyping of Coxiella-Like Endosymbionts in Ticks Collected from Animals and Vegetation in Zambia.
    Toshiya Kobayashi; Elisha Chatanga; Yongjin Qiu; Martin Simuunza; Masahiro Kajihara; Bernard Mudenda Hang'ombe; Yoshiki Eto; Ngonda Saasa; Akina Mori-Kajihara; Edgar Simulundu; Ayato Takada; Hirofumi Sawa; Ken Katakura; Nariaki Nonaka; Ryo Nakao
    Pathogens (Basel, Switzerland), 10, 6, 21 Jun. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Ticks are obligate ectoparasites as they require to feed on their host blood during some or all stages of their life cycle. In addition to the pathogens that ticks harbor and transmit to vertebrate hosts, they also harbor other seemingly nonpathogenic microorganisms including nutritional mutualistic symbionts. Tick nutritional mutualistic symbionts play important roles in the physiology of the host ticks as they are involved in tick reproduction and growth through the supply of B vitamins as well as in pathogen maintenance and propagation. Coxiella-like endosymbionts (CLEs) are the most widespread endosymbionts exclusively reported in ticks. Although CLEs have been investigated in ticks in other parts of the world, there is no report of their investigation in ticks in Zambia. To investigate the occurrence of CLEs, their maintenance, and association with host ticks in Zambia, 175 ticks belonging to six genera, namely Amblyomma, Argas, Haemaphysalis, Hyalomma, Ornithodoros, and Rhipicephalus, were screened for CLEs, followed by characterization of CLEs by multi-locus sequence typing of the five Coxiella housekeeping genes (dnaK, groEL, rpoB, 16S rRNA, and 23S rRNA). The results showed that 45.7% (n = 80) were positive for CLEs. The comparison of the tick 16S rDNA phylogenetic tree with that of the CLEs concatenated sequences showed that there was a strong correlation between the topology of the trees. The results suggest that most of the CLEs have evolved within tick species, supporting the vertical transmission phenomenon. However, the negative results for CLE in some ticks warrants further investigations of other endosymbionts that the ticks in Zambia may also harbor.
  • Immunization Coverage and Antibody Retention against Rabies in Domestic Dogs in Lusaka District, Zambia.
    Chiho Kaneko; Michihito Sasaki; Ryosuke Omori; Ryo Nakao; Chikako Kataoka-Nakamura; Ladslav Moonga; Joseph Ndebe; Walter Muleya; Edgar Simulundu; Bernard M Hang'ombe; George Dautu; Masahiro Kajihara; Akina Mori-Kajihara; Yongjin Qiu; Naoto Ito; Herman M Chambaro; Chihiro Sugimoto; Hideaki Higashi; Ayato Takada; Hirofumi Sawa; Aaron S Mweene; Norikazu Isoda
    Pathogens (Basel, Switzerland), 10, 6, 11 Jun. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Rabies remains endemic in Zambia. Despite conducting canine vaccinations in Lusaka district, the vaccination coverage and actual seropositivity in the dog population in Lusaka district are rarely evaluated. This study estimated the seropositivity-based immunization coverage in the owned dog population in Lusaka district using the expanded program on immunization cluster survey method. The time-series trend of neutralizing antibodies against rabies in vaccinated dogs was also evaluated. Of 366 dogs in 200 dog-owning households in Lusaka district, blood samples were collected successfully from 251 dogs. In the sampled dogs, 42.2% (106/251) had an antibody titer ≥0.5 IU/mL. When the 115 dogs whose blood was not collected were assumed to be seronegative, the minimum immunization coverage in Lusaka district's owned dog population was estimated at 29.0% (95% confidence interval: 22.4-35.5). It was also found that a single vaccination with certified vaccines is capable of inducing protective levels of antibodies. In contrast, higher antibody titers were observed in multiple-vaccinated dogs than in single-vaccinated dogs, coupled with the observation of a decline in antibody titer over time. These results suggest the importance of continuous booster immunization to maintain herd immunity and provide useful information to plan mass vaccination against rabies in Zambia.
  • Serologic and molecular evidence for circulation of Crimean-Congo hemorrhagic fever virus in ticks and cattle in Zambia.
    Masahiro Kajihara; Martin Simuunza; Ngonda Saasa; George Dautu; Akina Mori-Kajihara; Yongjin Qiu; Ryo Nakao; Yoshiki Eto; Hayato Furumoto; Bernard M Hang'ombe; Yasuko Orba; Hirofumi Sawa; Edgar Simulundu; Shuetsu Fukushi; Shigeru Morikawa; Masayuki Saijo; Jiro Arikawa; Swithine Kabilika; Mwaka Monze; Victor Mukonka; Aaron Mweene; Ayato Takada; Kumiko Yoshimatsu
    PLoS neglected tropical diseases, 15, 6, e0009452, Jun. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonosis with a high case fatality rate in humans. Although the disease is widely found in Africa, Europe, and Asia, the distribution and genetic diversity of CCHF virus (CCHFV) are poorly understood in African countries. To assess the risks of CCHF in Zambia, where CCHF has never been reported, epidemiologic studies in cattle and ticks were conducted. Through an indirect immunofluorescence assay, CCHFV nucleoprotein-specific serum IgG was detected in 8.4% (88/1,047) of cattle. Among 290 Hyalomma ticks, the principal vector of CCHFV, the viral genome was detected in 11 ticks. Phylogenetic analyses of the CCHFV S and M genome segments revealed that one of the detected viruses was a genetic reassortant between African and Asian strains. This study provides compelling evidence for the presence of CCHFV in Zambia and its transmission to vertebrate hosts.
  • Structural Insights into the Interaction of Filovirus Glycoproteins with the Endosomal Receptor Niemann-Pick C1: A Computational Study.
    Manabu Igarashi; Takatsugu Hirokawa; Yoshihiro Takadate; Ayato Takada
    Viruses, 13, 5, 14 May 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Filoviruses, including marburgviruses and ebolaviruses, have a single transmembrane glycoprotein (GP) that facilitates their entry into cells. During entry, GP needs to be cleaved by host proteases to expose the receptor-binding site that binds to the endosomal receptor Niemann-Pick C1 (NPC1) protein. The crystal structure analysis of the cleaved GP (GPcl) of Ebola virus (EBOV) in complex with human NPC1 has demonstrated that NPC1 has two protruding loops (loops 1 and 2), which engage a hydrophobic pocket on the head of EBOV GPcl. However, the molecular interactions between NPC1 and the GPcl of other filoviruses remain unexplored. In the present study, we performed molecular modeling and molecular dynamics simulations of NPC1 complexed with GPcls of two ebolaviruses, EBOV and Sudan virus (SUDV), and one marburgvirus, Ravn virus (RAVV). Similar binding structures were observed in the GPcl-NPC1 complexes of EBOV and SUDV, which differed from that of RAVV. Specifically, in the RAVV GPcl-NPC1 complex, the tip of loop 2 was closer to the pocket edge comprising residues at positions 79-88 of GPcl; the root of loop 1 was predicted to interact with P116 and Q144 of GPcl. Furthermore, in the SUDV GPcl-NPC1 complex, the tip of loop 2 was slightly closer to the residue at position 141 than those in the EBOV and RAVV GPcl-NPC1 complexes. These structural differences may affect the size and/or shape of the receptor-binding pocket of GPcl. Our structural models could provide useful information for improving our understanding the differences in host preference among filoviruses as well as contributing to structure-based drug design.
  • A Fc engineering approach to define functional humoral correlates of immunity against Ebola virus.
    Bronwyn M Gunn; Richard Lu; Matthew D Slein; Philipp A Ilinykh; Kai Huang; Caroline Atyeo; Sharon L Schendel; Jiyoung Kim; Caitlin Cain; Vicky Roy; Todd J Suscovich; Ayato Takada; Peter J Halfmann; Yoshihiro Kawaoka; Matthias G Pauthner; Mambu Momoh; Augustine Goba; Lansana Kanneh; Kristian G Andersen; John S Schieffelin; Donald Grant; Robert F Garry; Erica Ollmann Saphire; Alexander Bukreyev; Galit Alter
    Immunity, 54, 4, 815, 828, 13 Apr. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Protective Ebola virus (EBOV) antibodies have neutralizing activity and induction of antibody constant domain (Fc)-mediated innate immune effector functions. Efforts to enhance Fc effector functionality often focus on maximizing antibody-dependent cellular cytotoxicity, yet distinct combinations of functions could be critical for antibody-mediated protection. As neutralizing antibodies have been cloned from EBOV disease survivors, we sought to identify survivor Fc effector profiles to help guide Fc optimization strategies. Survivors developed a range of functional antibody responses, and we therefore applied a rapid, high-throughput Fc engineering platform to define the most protective profiles. We generated a library of Fc variants with identical antigen-binding fragments (Fabs) from an EBOV neutralizing antibody. Fc variants with antibody-mediated complement deposition and moderate natural killer (NK) cell activity demonstrated complete protective activity in a stringent in vivo mouse model. Our findings highlight the importance of specific effector functions in antibody-mediated protection, and the experimental platform presents a generalizable resource for identifying correlates of immunity to guide therapeutic antibody design.
  • Effect of varying storage conditions on diagnostic test outcomes of SARS-CoV-2.
    Satoshi Oguri; Shinichi Fujisawa; Keisuke Kamada; Sho Nakakubo; Yu Yamashita; Junichi Nakamura; Hiroshi Horii; Kazuki Sato; Mutsumi Nishida; Takanori Teshima; Yoichi Ohiro; Ayato Takada; Satoshi Konno
    The Journal of infection, 83, 1, 119, 145, 03 Apr. 2021, [Peer-reviewed], [International Magazine]
    English
  • Domestic dog demographics and estimates of canine vaccination coverage in a rural area of Zambia for the elimination of rabies.
    Chiho Kaneko; Ryosuke Omori; Michihito Sasaki; Chikako Kataoka-Nakamura; Edgar Simulundu; Walter Muleya; Ladslav Moonga; Joseph Ndebe; Bernard M Hang'ombe; George Dautu; Yongjin Qiu; Ryo Nakao; Masahiro Kajihara; Akina Mori-Kajihara; Herman M Chambaro; Hideaki Higashi; Chihiro Sugimoto; Hirofumi Sawa; Aaron S Mweene; Ayato Takada; Norikazu Isoda
    PLoS neglected tropical diseases, 15, 4, e0009222, Apr. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: An estimated 75% or more of the human rabies cases in Africa occur in rural settings, which underscores the importance of rabies control in these areas. Understanding dog demographics can help design strategies for rabies control and plan and conduct canine mass vaccination campaigns effectively in African countries. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional survey was conducted to investigate domestic dog demographics in Kalambabakali, in the rural Mazabuka District of Zambia. The population of ownerless dogs and the total achievable vaccination coverage among the total dog population was estimated using the capture-recapture-based Bayesian model by conducting a canine mass vaccination campaign. This study revealed that 29% of the domestic dog population was under one year old, and 57.7% of those were under three months old and thus were not eligible for the canine rabies vaccination in Zambia. The population growth was estimated at 15% per annum based on the cross-sectional household survey. The population of ownerless dogs was estimated to be small, with an ownerless-to-owned-dog ratio of 0.01-0.06 in the target zones. The achieved overall vaccination coverage from the first mass vaccination was estimated 19.8-51.6%. This low coverage was principally attributed to the owners' lack of information, unavailability, and dog-handling difficulties. The follow-up mass vaccination campaign achieved an overall coverage of 54.8-76.2%. CONCLUSIONS/SIGNIFICANCE: This paper indicates the potential for controlling canine rabies through mass vaccination in rural Zambia. Rabies education and responsible dog ownership are required to achieve high and sustainable vaccination coverage. Our findings also propose including puppies below three months old in the target population for rabies vaccination and emphasize that securing an annual enforcement of canine mass vaccination that reaches 70% coverage in the dog population is necessary to maintain protective herd immunity.
  • Prevalence and genetic diversity of Shibuyunji virus, a novel tick-borne phlebovirus identified in Zambia.
    Edgar Simulundu; Saidon Mbambara; Herman M Chambaro; Karen Sichibalo; Masahiro Kajihara; King S Nalubamba; Hirofumi Sawa; Ayato Takada; Katendi Changula; Simbarashe Chitanga
    Archives of virology, 166, 3, 915, 919, Mar. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Tick-borne pathogens are an emerging public health threat worldwide. However, information on tick-borne viruses is scanty in sub-Saharan Africa. Here, by RT-PCR, 363 ticks (Amblyomma, Hyalomma and Rhipicephalus) in the Namwala and Livingstone districts of Zambia were screened for tick-borne phleboviruses (TBPVs). TBPVs (L gene) were detected in 19 (5.2%) Rhipicephalus ticks in Namwala. All the detected TBPVs were Shibuyunji viruses. Phylogenetically, they were closely related to American dog tick phlebovirus. This study highlights the possible role of Rhipicephalus ticks as the main host of Shibuyunji virus and suggests that these viruses may be present outside the area where they were initially discovered.
  • Variation in the HA antigenicity of A(H1N1)pdm09-related swine influenza viruses.
    Ahmed Magdy Khalil; Reiko Yoshida; Tatsunori Masatani; Ayato Takada; Makoto Ozawa
    The Journal of general virology, 102, 3, Mar. 2021, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, Since the influenza pandemic in 2009, the causative agent 'A(H1N1)pdm09 virus', has been circulating in both human and swine populations. Although phylogenetic analyses of the haemagglutinin (HA) gene segment have revealed broader genetic diversity of A(H1N1)pdm09-related swine influenza A viruses (swIAVs) compared with human A(H1N1)pdm09 viruses, it remains unclear whether the genetic diversity reflects the antigenic differences in HA. To assess the impact of the diversity of the HA gene of A(H1N1)pdm09-related swIAVs on HA antigenicity, we characterized 12 swIAVs isolated in Japan from 2013 to 2018. We used a ferret antiserum and a panel of anti-HA mouse monoclonal antibodies (mAbs) raised against an early A(H1N1)pdm09 isolate. The neutralization assay with the ferret antiserum revealed that five of the 12 swIAVs were significantly different in their HA antigenicity from the early A(H1N1)pdm09 isolate. The mAbs also showed differential neutralization patterns depending on the swIAV strains. In addition, the single amino acid substitution at position 190 of HA, which was found in one of the five antigenically different swIAVs but not in human isolates, was shown to be one of the critical determinants for the antigenic difference of swIAV HAs. Two potential N-glycosylation sites at amino acid positions 185 and 276 of the HA molecule were identified in two antigenically different swIAVs. These results indicated that the genetic diversity of HA in the A(H1N1)pdm09-related swIAVs is associated with their HA antigenic variation. Our findings highlighted the need for surveillance to monitor the emergence of swIAV antigenic variants with public health importance.
  • An African tick flavivirus forming an independent clade exhibits unique exoribonuclease-resistant RNA structures in the genomic 3'-untranslated region.
    Hayato Harima; Yasuko Orba; Shiho Torii; Yongjin Qiu; Masahiro Kajihara; Yoshiki Eto; Naoya Matsuta; Bernard M Hang'ombe; Yuki Eshita; Kentaro Uemura; Keita Matsuno; Michihito Sasaki; Kentaro Yoshii; Ryo Nakao; William W Hall; Ayato Takada; Takashi Abe; Michael T Wolfinger; Martin Simuunza; Hirofumi Sawa
    Scientific reports, 11, 1, 4883, 4883, 01 Mar. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Tick-borne flaviviruses (TBFVs) infect mammalian hosts through tick bites and can cause various serious illnesses, such as encephalitis and hemorrhagic fevers, both in humans and animals. Despite their importance to public health, there is limited epidemiological information on TBFV infection in Africa. Herein, we report that a novel flavivirus, Mpulungu flavivirus (MPFV), was discovered in a Rhipicephalus muhsamae tick in Zambia. MPFV was found to be genetically related to Ngoye virus detected in ticks in Senegal, and these viruses formed a unique lineage in the genus Flavivirus. Analyses of dinucleotide contents of flaviviruses indicated that MPFV was similar to those of other TBFVs with a typical vertebrate genome signature, suggesting that MPFV may infect vertebrate hosts. Bioinformatic analyses of the secondary structures in the 3'-untranslated regions (UTRs) revealed that MPFV exhibited unique exoribonuclease-resistant RNA (xrRNA) structures. Utilizing biochemical approaches, we clarified that two xrRNA structures of MPFV in the 3'-UTR could prevent exoribonuclease activity. In summary, our findings provide new information regarding the geographical distribution of TBFV and xrRNA structures in the 3'-UTR of flaviviruses.
  • Tim4 recognizes carbon nanotubes and mediates phagocytosis leading to granuloma formation.
    Satoshi Omori; Misato Tsugita; Yasuto Hoshikawa; Masanobu Morita; Fumiya Ito; Shin-Ichiro Yamaguchi; Qilin Xie; Osamu Noyori; Tomoya Yamaguchi; Ayato Takada; Tatsuya Saitoh; Shinya Toyokuni; Hisaya Akiba; Shigekazu Nagata; Kengo Kinoshita; Masafumi Nakayama
    Cell reports, 34, 6, 108734, 108734, 09 Feb. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Macrophage recognition and phagocytosis of crystals is critical for the associated fibrosis and cancer. Of note, multi-walled carbon nanotubes (MWCNTs), the highly representative products of nanotechnology, induce macrophage NLRP3 inflammasome activation and cause asbestosis-like pathogenesis. However, it remains largely unknown how macrophages efficiently recognize MWCNTs on their cell surfaces. Here, we identify by a targeted screening of phagocyte receptors the phosphatidylserine receptors T cell immunoglobulin mucin 4 (Tim4) and Tim1 as the pattern-recognition receptors for carbon crystals. Docking simulation studies reveal spatiotemporally stable interfaces between aromatic residues in the extracellular IgV domain of Tim4 and one-dimensional carbon crystals. Further, CRISPR-Cas9-mediated deletion of Tim4 and Tim1 reveals that Tim4, but not Tim1, critically contributes to the recognition of MWCNTs by peritoneal macrophages and to granuloma development in a mouse model of direct mesothelium exposure to MWCNTs. These results suggest that Tim4 recognizes MWCNTs through aromatic interactions and mediates phagocytosis leading to granulomas.
  • Purification of Crimean-Congo hemorrhagic fever virus nucleoprotein and its utility for serological diagnosis.
    Boniface Pongombo Lombe; Hiroko Miyamoto; Takeshi Saito; Reiko Yoshida; Rashid Manzoor; Masahiro Kajihara; Masayuki Shimojima; Shuetsu Fukushi; Shigeru Morikawa; Tomoki Yoshikawa; Takeshi Kurosu; Masayuki Saijo; Qing Tang; Justin Masumu; David Hawman; Heinz Feldmann; Ayato Takada
    Scientific reports, 11, 1, 2324, 2324, 27 Jan. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Crimean-Congo hemorrhagic fever virus (CCHFV) causes a zoonotic disease, Crimean-Congo hemorrhagic fever (CCHF) endemic in Africa, Asia, the Middle East, and Southeastern Europe. However, the prevalence of CCHF is not monitored in most of the endemic countries due to limited availability of diagnostic assays and biosafety regulations required for handling infectious CCHFV. In this study, we established a protocol to purify the recombinant CCHFV nucleoprotein (NP), which is antigenically highly conserved among multiple lineages/clades of CCHFVs and investigated its utility in an enzyme-linked immunosorbent assay (ELISA) to detect CCHFV-specific antibodies. The NP gene was cloned into the pCAGGS mammalian expression plasmid and human embryonic kidney 293 T cells were transfected with the plasmid. The expressed NP molecule was purified from the cell lysate using cesium-chloride gradient centrifugation. Purified NP was used as the antigen for the ELISA to detect anti-CCHFV IgG. Using the CCHFV NP-based ELISA, we efficiently detected CCHFV-specific IgG in anti-NP rabbit antiserum and CCHFV-infected monkey serum. When compared to the commercially available Blackbox CCHFV IgG ELISA kit, our assay showed equivalent performance in detecting CCHFV-specific IgG in human sera. These results demonstrate the usefulness of our CCHFV NP-based ELISA for seroepidemiological studies.
  • First COVID-19 case in Zambia - Comparative phylogenomic analyses of SARS-CoV-2 detected in African countries.
    Edgar Simulundu; Francis Mupeta; Pascalina Chanda-Kapata; Ngonda Saasa; Katendi Changula; Walter Muleya; Simbarashe Chitanga; Miniva Mwanza; Paul Simusika; Herman Chambaro; Benjamin Mubemba; Masahiro Kajihara; Duncan Chanda; Lloyd Mulenga; Sombo Fwoloshi; Aaron Lunda Shibemba; Fred Kapaya; Paul Zulu; Kunda Musonda; Mwaka Monze; Nyambe Sinyange; Mazyanga L Mazaba; Muzala Kapin'a; Peter J Chipimo; Raymond Hamoonga; Davie Simwaba; William Ngosa; Albertina N Morales; Nkomba Kayeyi; John Tembo; Mathew Bates; Yasuko Orba; Hirofumi Sawa; Ayato Takada; King S Nalubamba; Kennedy Malama; Victor Mukonka; Alimuddin Zumla; Nathan Kapata
    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 102, 455, 459, Jan. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Since its first discovery in December 2019 in Wuhan, China, COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread rapidly worldwide. While African countries were relatively spared initially, the initial low incidence of COVID-19 cases was not sustained for long due to continuing travel links between China, Europe and Africa. In preparation, Zambia had applied a multisectoral national epidemic disease surveillance and response system resulting in the identification of the first case within 48 h of the individual entering the country by air travel from a trip to France. Contact tracing showed that SARS-CoV-2 infection was contained within the patient's household, with no further spread to attending health care workers or community members. Phylogenomic analysis of the patient's SARS-CoV-2 strain showed that it belonged to lineage B.1.1., sharing the last common ancestor with SARS-CoV-2 strains recovered from South Africa. At the African continental level, our analysis showed that B.1 and B.1.1 lineages appear to be predominant in Africa. Whole genome sequence analysis should be part of all surveillance and case detection activities in order to monitor the origin and evolution of SARS-CoV-2 lineages across Africa.
  • A Novel Mechanism Underlying Antiviral Activity of an Influenza Virus M2-Specific Antibody.
    Rashid Manzoor; Nao Eguchi; Reiko Yoshida; Hiroichi Ozaki; Tatsunari Kondoh; Kosuke Okuya; Hiroko Miyamoto; Ayato Takada
    Journal of virology, 95, 1, 09 Dec. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Protective immunity against influenza A viruses (IAVs) generally depends on antibodies to the major envelope glycoprotein, hemagglutinin (HA), whose antigenicity is distinctive among IAV subtypes. On the other hand, the matrix 2 (M2) protein is antigenically highly conserved and has been studied as an attractive vaccine antigen to confer cross-protective immunity against multiple subtypes of IAVs. However, antiviral mechanisms of M2-specific antibodies are not fully understood. Here, we report the molecular basis of antiviral activity of an M2-specific monoclonal antibody (MAb), rM2ss23. We first found that rM2ss23 inhibited A/Aichi/2/1968 (H3N2) (Aichi) but not A/PR/8/1934 (H1N1) (PR8) replication. rM2ss23 altered the cell surface distribution of M2, likely by cross-linking the molecules, and interfered with the colocalization of HA and M2, resulting in reduced budding of progeny viruses. However, these effects were not observed for another strain, PR8, despite the binding capacity of rM2ss23 to PR8 M2. Interestingly, HA was also involved in the resistance of PR8 to rM2ss23. We also found that two amino acid residues at positions 54 and 57 in the M2 cytoplasmic tail were critical for the insensitivity of PR8 to rM2ss2. These findings suggest that the disruption of the M2-HA colocalization on infected cells and subsequent reduction of virus budding is one of the principal mechanisms of antiviral activity of M2-specific antibodies and that anti-M2 antibody-sensitive and -resistant IAVs have different properties in the interaction between M2 and HA.IMPORTANCE Although the IAV HA is the major target of neutralizing antibodies, most of the antibodies are HA subtype specific, restricting the potential of HA-based vaccines. On the contrary, the IAV M2 protein has been studied as a vaccine antigen to confer cross-protective immunity against IAVs with multiple HA subtypes, since M2 is antigenically conserved. Although a number of studies highlight the protective role of anti-HA neutralizing and nonneutralizing antibodies, precise information on the molecular mechanism of action of M2-specific antibodies is still obscure. In this study, we found that an anti-M2 antibody interfered with the HA-M2 association, which is important for efficient budding of progeny virus particles from infected cells. The antiviral activity was IAV strain dependent despite the similar binding capacity of the antibody to M2, and, interestingly, HA was involved in susceptibility to the antibody. Our data provide a novel mechanism underlying antiviral activity of M2-specific antibodies.
  • 2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.
    Jens H Kuhn; Scott Adkins; Daniela Alioto; Sergey V Alkhovsky; Gaya K Amarasinghe; Simon J Anthony; Tatjana Avšič-Županc; María A Ayllón; Justin Bahl; Anne Balkema-Buschmann; Matthew J Ballinger; Tomáš Bartonička; Christopher Basler; Sina Bavari; Martin Beer; Dennis A Bente; Éric Bergeron; Brian H Bird; Carol Blair; Kim R Blasdell; Steven B Bradfute; Rachel Breyta; Thomas Briese; Paul A Brown; Ursula J Buchholz; Michael J Buchmeier; Alexander Bukreyev; Felicity Burt; Nihal Buzkan; Charles H Calisher; Mengji Cao; Inmaculada Casas; John Chamberlain; Kartik Chandran; Rémi N Charrel; Biao Chen; Michela Chiumenti; Il-Ryong Choi; J Christopher S Clegg; Ian Crozier; John V da Graça; Elena Dal Bó; Alberto M R Dávila; Juan Carlos de la Torre; Xavier de Lamballerie; Rik L de Swart; Patrick L Di Bello; Nicholas Di Paola; Francesco Di Serio; Ralf G Dietzgen; Michele Digiaro; Valerian V Dolja; Olga Dolnik; Michael A Drebot; Jan Felix Drexler; Ralf Dürrwald; Lucie Dufkova; William G Dundon; W Paul Duprex; John M Dye; Andrew J Easton; Hideki Ebihara; Toufic Elbeaino; Koray Ergünay; Jorlan Fernandes; Anthony R Fooks; Pierre B H Formenty; Leonie F Forth; Ron A M Fouchier; Juliana Freitas-Astúa; Selma Gago-Zachert; George Fú Gāo; María Laura García; Adolfo García-Sastre; Aura R Garrison; Aiah Gbakima; Tracey Goldstein; Jean-Paul J Gonzalez; Anthony Griffiths; Martin H Groschup; Stephan Günther; Alexandro Guterres; Roy A Hall; John Hammond; Mohamed Hassan; Jussi Hepojoki; Satu Hepojoki; Udo Hetzel; Roger Hewson; Bernd Hoffmann; Seiji Hongo; Dirk Höper; Masayuki Horie; Holly R Hughes; Timothy H Hyndman; Amara Jambai; Rodrigo Jardim; Dàohóng Jiāng; Qi Jin; Gilda B Jonson; Sandra Junglen; Serpil Karadağ; Karen E Keller; Boris Klempa; Jonas Klingström; Gary Kobinger; Hideki Kondō; Eugene V Koonin; Mart Krupovic; Gael Kurath; Ivan V Kuzmin; Lies Laenen; Robert A Lamb; Amy J Lambert; Stanley L Langevin; Benhur Lee; Elba R S Lemos; Eric M Leroy; Dexin Li; Jiànróng Lǐ; Mifang Liang; Wénwén Liú; Yàn Liú; Igor S Lukashevich; Piet Maes; William Marciel de Souza; Marco Marklewitz; Sergio H Marshall; Giovanni P Martelli; Robert R Martin; Shin-Yi L Marzano; Sébastien Massart; John W McCauley; Nicole Mielke-Ehret; Angelantonio Minafra; Maria Minutolo; Ali Mirazimi; Hans-Peter Mühlbach; Elke Mühlberger; Rayapati Naidu; Tomohide Natsuaki; Beatriz Navarro; José A Navarro; Sergey V Netesov; Gabriele Neumann; Norbert Nowotny; Márcio R T Nunes; Are Nylund; Arnfinn L Økland; Renata C Oliveira; Gustavo Palacios; Vicente Pallas; Bernadett Pályi; Anna Papa; Colin R Parrish; Alex Pauvolid-Corrêa; Janusz T Pawęska; Susan Payne; Daniel R Pérez; Florian Pfaff; Sheli R Radoshitzky; Aziz-Ul Rahman; Pedro L Ramos-González; Renato O Resende; Carina A Reyes; Bertus K Rima; Víctor Romanowski; Gabriel Robles Luna; Paul Rota; Dennis Rubbenstroth; Jonathan A Runstadler; Daniel Ruzek; Sead Sabanadzovic; Jiří Salát; Amadou Alpha Sall; Maria S Salvato; Kamil Sarpkaya; Takahide Sasaya; Martin Schwemmle; Muhammad Z Shabbir; Xiǎohóng Shí; Zhènglì Shí; Yukio Shirako; Peter Simmonds; Jana Širmarová; Manuela Sironi; Sophie Smither; Teemu Smura; Jin-Won Song; Kirsten M Spann; Jessica R Spengler; Mark D Stenglein; David M Stone; Petra Straková; Ayato Takada; Robert B Tesh; Natalie J Thornburg; Keizō Tomonaga; Noël Tordo; Jonathan S Towner; Massimo Turina; Ioannis Tzanetakis; Rainer G Ulrich; Anna Maria Vaira; Bernadette van den Hoogen; Arvind Varsani; Nikos Vasilakis; Martin Verbeek; Victoria Wahl; Peter J Walker; Hui Wang; Jianwei Wang; Xifeng Wang; Lin-Fa Wang; Tàiyún Wèi; Heather Wells; Anna E Whitfield; John V Williams; Yuri I Wolf; Zhìqiáng Wú; Xin Yang; Xīnglóu Yáng; Xuejie Yu; Natalya Yutin; F Murilo Zerbini; Tong Zhang; Yong-Zhen Zhang; Guohui Zhou; Xueping Zhou
    Archives of virology, 165, 12, 3023, 3072, Dec. 2020, [Peer-reviewed], [International Magazine]
    English, In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
  • A biaryl sulfonamide derivative as a novel inhibitor of filovirus infection.
    Mao Isono; Wakako Furuyama; Makoto Kuroda; Tatsunari Kondoh; Manabu Igarashi; Masahiro Kajihara; Reiko Yoshida; Rashid Manzoor; Kosuke Okuya; Hiroko Miyamoto; Heinz Feldmann; Andrea Marzi; Masahiro Sakaitani; Asuka Nanbo; Ayato Takada
    Antiviral research, 183, 104932, 104932, Nov. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Ebolaviruses and marburgviruses, members of the family Filoviridae, are known to cause fatal diseases often associated with hemorrhagic fever. Recent outbreaks of Ebola virus disease in West African countries and the Democratic Republic of the Congo have made clear the urgent need for the development of therapeutics and vaccines against filoviruses. Using replication-incompetent vesicular stomatitis virus (VSV) pseudotyped with the Ebola virus (EBOV) envelope glycoprotein (GP), we screened a chemical compound library to obtain new drug candidates that inhibit filoviral entry into target cells. We discovered a biaryl sulfonamide derivative that suppressed in vitro infection mediated by GPs derived from all known human-pathogenic filoviruses. To determine the inhibitory mechanism of the compound, we monitored each entry step (attachment, internalization, and membrane fusion) using lipophilic tracer-labeled ebolavirus-like particles and found that the compound efficiently blocked fusion between the viral envelope and the endosomal membrane during cellular entry. However, the compound did not block the interaction of GP with the Niemann-Pick C1 protein, which is believed to be the receptor of filoviruses. Using replication-competent VSVs pseudotyped with EBOV GP, we selected escape mutants and identified two EBOV GP amino acid residues (positions 47 and 66) important for the interaction with this compound. Interestingly, these amino acid residues were located at the base region of the GP trimer, suggesting that the compound might interfere with the GP conformational change required for membrane fusion. These results suggest that this biaryl sulfonamide derivative is a novel fusion inhibitor and a possible drug candidate for the development of a pan-filovirus therapeutic.
  • Evidence for exposure of asymptomatic domestic pigs to African swine fever virus during an inter-epidemic period in Zambia.
    Herman M Chambaro; Michihito Sasaki; Yona Sinkala; Gabriel Gonzalez; David Squarre; Paul Fandamu; Caesar Lubaba; Liywalii Mataa; Misheck Shawa; Kabemba E Mwape; Sarah Gabriël; Mwelwa Chembensofu; Michael J Carr; William W Hall; Yongjin Qiu; Masahiro Kajihara; Ayato Takada; Yasuko Orba; Edgar Simulundu; Hirofumi Sawa
    Transboundary and emerging diseases, 67, 6, 2741, 2752, Nov. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, African swine fever (ASF) causes persistent outbreaks in endemic and non-endemic regions in Zambia. However, the epidemiology of the disease is poorly understood, particularly during the inter-epidemic periods. We conducted surveillance for ASF in asymptomatic domestic pigs and soft ticks in selected Zambian provinces. While serum samples (n = 1,134) were collected from crossbred pigs from all study sites between 2014 and 2017, whole blood (n = 300) was collected from both crossbred and indigenous pigs in Eastern Province (EP) in 2017. Soft ticks were collected from Mosi-oa-Tunya National Park in Southern Province (SP) in 2019. Sera were screened for antibodies against ASF by ELISA while genome detection in whole blood and soft ticks was conducted by PCR. Ticks were identified morphologically and by phylogenetic analysis of the 16S rRNA gene. Seroprevalence was highest in EP (50.9%, 95% CI [47.0-54.9]) compared to significantly lower rates in SP (2.9%, 95% CI [1.6-5.1]). No antibodies to ASFV were detected in Lusaka Province. In EP, the prevalence of ASFV genome was 11.7% (35/300), significantly higher (OR = 6.2, 95% CI [2.4-16.6]) in indigenous pigs compared to crossbred pigs. The pooled prevalence of ASFV genome in ticks was 11.0%, 95% CI [8.5-13.9]. Free-range husbandry system was the only factor that was significantly associated with seropositive (p < .0001, OR = 39.3) and PCR-positive results (p < .001, OR = 5.7). Phylogenetically, based on the p72 gene, ASFV from Ornithodoros moubata ticks detected in this study belonged to genotype I, but they separated into two distinct clusters. Besides confirming ASF endemicity in EP and the presence of ASFV-infected ticks in SP, these results provide evidence for exposure of domestic pigs to ASFV in non-endemic regions during the inter-epidemic period.
  • Receptor-Mediated Host Cell Preference of a Bat-Derived Filovirus, Lloviu Virus.
    Yoshihiro Takadate; Rashid Manzoor; Takeshi Saito; Yurie Kida; Junki Maruyama; Tatsunari Kondoh; Hiroko Miyamoto; Hirohito Ogawa; Masahiro Kajihara; Manabu Igarashi; Ayato Takada
    Microorganisms, 8, 10, 05 Oct. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Lloviu virus (LLOV), a bat-derived filovirus that is phylogenetically distinct from human pathogenic filoviruses such as Ebola virus (EBOV) and Marburg virus (MARV), was discovered in Europe. However, since infectious LLOV has never been isolated, the biological properties of this virus remain poorly understood. We found that vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of LLOV (VSV-LLOV) showed higher infectivity in one bat (Miniopterus sp.)-derived cell line than in the other bat-derived cell lines tested, which was distinct from the tropism of VSV pseudotyped with EBOV (VSV-EBOV) and MARV GPs. We then focused on the interaction between GP and Niemann-Pick C1 (NPC1) protein, one of the cellular receptors of filoviruses. We introduced the Miniopterus bat and human NPC1 genes into NPC1-knockout Vero E6 cells and their susceptibilities to the viruses were compared. The cell line expressing the bat NPC1 showed higher susceptibility to VSV-LLOV than that expressing human NPC1, whereas the opposite preference was seen for VSV-EBOV. Using a site-directed mutagenesis approach, amino acid residues involved in the differential tropism were identified in the NPC1 and GP molecules. Our results suggest that the interaction between GP and NPC1 is an important factor in the tropism of LLOV to a particular bat species.
  • Characterization of mammalian orthoreoviruses isolated from faeces of pigs in Zambia.
    Hayato Harima; Michihito Sasaki; Masahiro Kajihara; Gabriel Gonzalez; Edgar Simulundu; Eugene C Bwalya; Yongjin Qiu; Kosuke Okuya; Mao Isono; Yasuko Orba; Ayato Takada; Bernard M Hang'ombe; Aaron S Mweene; Hirofumi Sawa
    The Journal of general virology, 101, 10, 1027, 1036, Oct. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Mammalian orthoreovirus (MRV) has been identified in humans, livestock and wild animals; this wide host range allows individual MRV to transmit into multiple species. Although several interspecies transmission and genetic reassortment events of MRVs among humans, livestock and wildlife have been reported, the genetic diversity and geographic distribution of MRVs in Africa are poorly understood. In this study, we report the first isolation and characterization of MRVs circulating in a pig population in Zambia. In our screening, MRV genomes were detected in 19.7 % (29/147) of faecal samples collected from pigs by reverse transcription PCR. Three infectious MRV strains (MRV-85, MRV-96 and MRV-117) were successfully isolated, and their complete genomes were sequenced. Recombination analyses based on the complete genome sequences of the isolated MRVs demonstrated that MRV-96 shared the S3 segment with a different MRV isolated from bats, and that the L1 and M3 segments of MRV-117 originated from bat and human MRVs, respectively. Our results suggest that the isolated MRVs emerged through genetic reassortment events with interspecies transmission. Given the lack of information regarding MRVs in Africa, further surveillance of MRVs circulating among humans, domestic animals and wildlife is required to assess potential risk for humans and animals.
  • Avian Influenza Viruses Detected in Birds in Sub-Saharan Africa: A Systematic Review.
    Annie Kalonda; Ngonda Saasa; Panji Nkhoma; Masahiro Kajihara; Hirofumi Sawa; Ayato Takada; Edgar Simulundu
    Viruses, 12, 9, 07 Sep. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, In the recent past, sub-Saharan Africa has not escaped the devastating effects of avian influenza virus (AIV) in poultry and wild birds. This systematic review describes the prevalence, spatiotemporal distribution, and virus subtypes detected in domestic and wild birds for the past two decades (2000-2019). We collected data from three electronic databases, PubMed, SpringerLink electronic journals and African Journals Online, using the Preferred Reporting Items for Systematic reviews and Meta-Analyses protocol. A total of 1656 articles were reviewed, from which 68 were selected. An overall prevalence of 3.0% AIV in birds was observed. The prevalence varied between regions and ranged from 1.1% to 7.1%. The Kruskal-Wallis and Wilcoxon signed-rank sum test showed no significant difference in the prevalence of AIV across regions, χ2(3) = 5.237, p = 0.1553 and seasons, T = 820, z = -1.244, p = 0.2136. Nineteen hemagglutinin/neuraminidase subtype combinations were detected during the reviewed period, with southern Africa recording more diverse AIV subtypes than other regions. The most detected subtype was H5N1, followed by H9N2, H5N2, H5N8 and H6N2. Whilst these predominant subtypes were mostly detected in domestic poultry, H1N6, H3N6, H4N6, H4N8, H9N1 and H11N9 were exclusively detected in wild birds. Meanwhile, H5N1, H5N2 and H5N8 were detected in both wild and domestic birds suggesting circulation of these subtypes among wild and domestic birds. Our findings provide critical information on the eco-epidemiology of AIVs that can be used to improve surveillance strategies for the prevention and control of avian influenza in sub-Saharan Africa.
  • A complement component C1q-mediated mechanism of antibody-dependent enhancement of Ebola virus infection.
    Wakako Furuyama; Asuka Nanbo; Junki Maruyama; Andrea Marzi; Ayato Takada
    PLoS neglected tropical diseases, 14, 9, e0008602, Sep. 2020, [International Magazine]
    English, Scientific journal, Besides the common Fc receptor (FcR)-mediated mechanism of antibody-dependent enhancement (ADE), Ebola virus (EBOV) is known to utilize the complement component C1q for ADE of infection. This mechanism is FcR-independent and mediated by cross-linking of virus-antibody-C1q complexes to cell surface C1q receptors, leading to enhanced viral entry into cells. Using confocal microscopy, we found that virus-like particles (VLPs) consisting of EBOV glycoprotein, nucleoprotein, and matrix protein attached to the surface of human kidney 293 cells more efficiently in the presence of an ADE monoclonal antibody and C1q than with the antibody or C1q alone, and that there was no significant difference in the efficiency of VLP uptake into endosomes between the C1q-mediated ADE and non-ADE entry. Accordingly, both ADE and non-ADE infection were similarly decreased by inhibitors of the signaling pathways known to be required for endocytosis. These results suggest that C1q-mediated ADE of EBOV infection is simply caused by increased attachment of virus particles to the cell surface, which is distinct from the mechanism of FcR-mediated ADE requiring intracellular signaling to promote phagocytosis/macropinocytosis.
  • Modeling the efficiency of filovirus entry into cells in vitro: Effects of SNP mutations in the receptor molecule.
    Kwang Su Kim; Tatsunari Kondoh; Yusuke Asai; Ayato Takada; Shingo Iwami
    PLoS computational biology, 16, 9, e1007612, Sep. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Interaction between filovirus glycoprotein (GP) and the Niemann-Pick C1 (NPC1) protein is essential for membrane fusion during virus entry. Some single-nucleotide polymorphism (SNPs) in two surface-exposed loops of NPC1 are known to reduce viral infectivity. However, the dependence of differences in entry efficiency on SNPs remains unclear. Using vesicular stomatitis virus pseudotyped with Ebola and Marburg virus GPs, we investigated the cell-to-cell spread of viruses in cultured cells expressing NPC1 or SNP derivatives. Eclipse and virus-producing phases were assessed by in vitro infection experiments, and we developed a mathematical model describing spatial-temporal virus spread. This mathematical model fit the plaque radius data well from day 2 to day 6. Based on the estimated parameters, we found that SNPs causing the P424A and D508N substitutions in NPC1 most effectively reduced the entry efficiency of Ebola and Marburg viruses, respectively. Our novel approach could be broadly applied to other virus plaque assays.
  • A Surrogate Animal Model for Screening of Ebola and Marburg Glycoprotein-Targeting Drugs Using Pseudotyped Vesicular Stomatitis Viruses.
    Takeshi Saito; Junki Maruyama; Noriyo Nagata; Mao Isono; Kosuke Okuya; Yoshihiro Takadate; Yurie Kida; Hiroko Miyamoto; Akina Mori-Kajihara; Takanari Hattori; Wakako Furuyama; Shinya Ogawa; Shigeru Iida; Ayato Takada
    Viruses, 12, 9, 22 Aug. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Filoviruses, including Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic fever in humans and nonhuman primates with high mortality rates. There is no approved therapy against these deadly viruses. Antiviral drug development has been hampered by the requirement of a biosafety level (BSL)-4 facility to handle infectious EBOV and MARV because of their high pathogenicity to humans. In this study, we aimed to establish a surrogate animal model that can be used for anti-EBOV and -MARV drug screening under BSL-2 conditions by focusing on the replication-competent recombinant vesicular stomatitis virus (rVSV) pseudotyped with the envelope glycoprotein (GP) of EBOV (rVSV/EBOV) and MARV (rVSV/MARV), which has been investigated as vaccine candidates and thus widely used in BSL-2 laboratories. We first inoculated mice, rats, and hamsters intraperitoneally with rVSV/EBOV and found that only hamsters showed disease signs and succumbed within 4 days post-infection. Infection with rVSV/MARV also caused lethal infection in hamsters. Both rVSV/EBOV and rVSV/MARV were detected at high titers in multiple organs including the liver, spleen, kidney, and lungs of infected hamsters, indicating acute and systemic infection resulting in fatal outcomes. Therapeutic effects of passive immunization with an anti-EBOV neutralizing antibody were specifically observed in rVSV/EBOV-infected hamsters. Thus, this animal model is expected to be a useful tool to facilitate in vivo screening of anti-filovirus drugs targeting the GP molecule.
  • Genetic and antigenic characterization of H5 and H7 avian influenza viruses isolated from migratory waterfowl in Mongolia from 2017 to 2019.
    Ankhanbaatar Ulaankhuu; Enkhbold Bazarragchaa; Masatoshi Okamatsu; Takahiro Hiono; Khishgee Bodisaikhan; Tsolmon Amartuvshin; Jargalsaikhan Tserenjav; Tsogtbaatar Urangoo; Khanui Buyantogtokh; Keita Matsuno; Takanari Hattori; Tatsunari Kondoh; Masahiro Sato; Yoshihiro Takadate; Shiho Torii; Mao Isono; Kosuke Okuya; Takeshi Saito; Nodoka Kasajima; Yurie Kida; Junki Maruyama; Manabu Igarashi; Ayato Takada; Hiroshi Kida; Damdinjav Batchuluun; Yoshihiro Sakoda
    Virus genes, 56, 4, 472, 479, Aug. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The circulation of highly pathogenic avian influenza viruses (HPAIVs) of various subtypes (e.g., H5N1, H5N6, H5N8, and H7N9) in poultry remains a global concern for animal and public health. Migratory waterfowls play important roles in the transmission of these viruses across countries. To monitor virus spread by wild birds, active surveillance for avian influenza in migratory waterfowl was conducted in Mongolia from 2015 to 2019. In total, 5000 fecal samples were collected from lakesides in central Mongolia, and 167 influenza A viruses were isolated. Two H5N3, four H7N3, and two H7N7 viruses were characterized in this study. The amino acid sequence at hemagglutinin (HA) cleavage site of those isolates suggested low pathogenicity in chickens. Phylogenetic analysis revealed that all H5 and H7 viruses were closely related to recent H5 and H7 low pathogenic avian influenza viruses (LPAIVs) isolated from wild birds in Asia and Europe. Antigenicity of H7Nx was similar to those of typical non-pathogenic avian influenza viruses (AIVs). While HPAIVs or A/Anhui/1/2013 (H7N9)-related LPAIVs were not detected in migratory waterfowl in Mongolia, sporadic introductions of AIVs including H5 and H7 viruses into Mongolia through the wild bird migration were identified. Thus, continued monitoring of H5 and H7 AIVs in both domestic and wild birds is needed for the early detection of HPAIVs spread into the country.
  • Comparative Analyses of the Antiviral Activities of IgG and IgA Antibodies to Influenza A Virus M2 Protein.
    Kosuke Okuya; Nao Eguchi; Rashid Manzoor; Reiko Yoshida; Shinji Saito; Tadaki Suzuki; Michihito Sasaki; Takeshi Saito; Yurie Kida; Akina Mori-Kajihara; Hiroko Miyamoto; Osamu Ichii; Masahiro Kajihara; Hideaki Higashi; Ayato Takada
    Viruses, 12, 7, 20 Jul. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, The influenza A virus (IAV) matrix-2 (M2) protein is an antigenically conserved viral envelope protein that plays an important role in virus budding together with another envelope protein, hemagglutinin (HA). An M2-specific mouse monoclonal IgG antibody, rM2ss23, which binds to the ectodomain of the M2 protein, has been shown to be a non-neutralizing antibody, but inhibits plaque formation of IAV strains. In this study, we generated chimeric rM2ss23 (ch-rM2ss23) IgG and IgA antibodies with the same variable region and compared their antiviral activities. Using gel chromatography, ch-rM2ss23 IgA were divided into three antibody subsets: monomeric IgA (m-IgA), dimeric IgA (d-IgA), and trimeric and tetrameric IgA (t/q-IgA). We found that t/q-IgA had a significantly higher capacity to reduce the plaque size of IAVs than IgG and m-IgA, most likely due to the decreased number of progeny virus particles produced from infected cells. Interestingly, HA-M2 colocalization was remarkably reduced on the infected cell surface in the presence of ch-rM2ss23 antibodies. These results indicate that anti-M2 polymeric IgA restricts IAV budding more efficiently than IgG and suggest a role of anti-M2 IgA in cross-protective immunity to IAVs.
  • Isolation of Candidatus Bartonella rousetti and Other Bat-associated Bartonellae from Bats and Their Flies in Zambia.
    Yongjin Qiu; Masahiro Kajihara; Ryo Nakao; Evans Mulenga; Hayato Harima; Bernard Mudenda Hang'ombe; Yoshiki Eto; Katendi Changula; Daniel Mwizabi; Hirofumi Sawa; Hideaki Higashi; Aaron Mweene; Ayato Takada; Martin Simuunza; Chihiro Sugimoto
    Pathogens (Basel, Switzerland), 9, 6, 13 Jun. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Bat-associated bartonellae, including Bartonella mayotimonensis and Candidatus Bartonella rousetti, were recently identified as emerging and potential zoonotic agents, respectively. However, there is no report of bat-associated bartonellae in Zambia. Thus, we aimed to isolate and characterize Bartonella spp. from bats and bat flies captured in Zambia by culturing and PCR. Overall, Bartonella spp. were isolated from six out of 36 bats (16.7%), while Bartonella DNA was detected in nine out of 19 bat flies (47.3%). Subsequent characterization using a sequence of five different genes revealed that three isolates obtained from Egyptian fruit bats (Rousettus aegyptiacus) were Ca. B. rousetti. The isolates obtained from insectivorous bats (Macronycteris vittatus) were divided into two previously unclassified bat-associated bartonellae. A phylogenetic analysis of the six genotypes of Bartonella gltA sequences from nine pathogen-positive bat flies revealed that three genotypes belonged to the same clades as bat-associated bartonellae, including Ca. B. rousetti. The other three genotypes represented arthropod-associated bartonellae, which have previously been isolated only from ectoparasites. We demonstrated that Ca. B. rousetti is maintained between bats (R. aegyptiacus) and bat flies in Zambia. Continuous surveillance of Bartonella spp. in bats and serological surveys in humans in Africa are warranted to evaluate the public health importance of bat-associated bartonellae.
  • Host ESCRT factors are recruited during chikungunya virus infection and are required for the intracellular viral replication cycle.
    Shiho Torii; Yasuko Orba; Michihito Sasaki; Koshiro Tabata; Yuji Wada; Michael Carr; Jody Hobson-Peters; Roy A Hall; Ayato Takada; Takasuke Fukuhara; Yoshiharu Matsuura; William W Hall; Hirofumi Sawa
    The Journal of biological chemistry, 295, 23, 7941, 7957, 05 Jun. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Chikungunya fever is a re-emerging zoonotic disease caused by chikungunya virus (CHIKV), a member of the Alphavirus genus in the Togaviridae family. Only a few studies have reported on the host factors required for intracellular CHIKV trafficking. Here, we conducted an imaging-based siRNA screen to identify human host factors for intracellular trafficking that are involved in CHIKV infection, examined their interactions with CHIKV proteins, and investigated the contributions of these proteins to CHIKV infection. The results of the siRNA screen revealed that host endosomal sorting complexes required for transport (ESCRT) proteins are recruited during CHIKV infection. Co-immunoprecipitation analyses revealed that both structural and nonstructural CHIKV proteins interact with hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a component of the ESCRT-0 complex. We also observed that HGS co-localizes with the E2 protein of CHIKV and with dsRNA, a marker of the replicated CHIKV genome. Results from gene knockdown analyses indicated that, along with other ESCRT factors, HGS facilitates both genome replication and post-translational steps during CHIKV infection. Moreover, we show that ESCRT factors are also required for infections with other alphaviruses. We conclude that during CHIKV infection, several ESCRT factors are recruited via HGS and are involved in viral genome replication and post-translational processing of viral proteins.
  • Prevalence and genotypic characterization of Giardia duodenalis isolates from asymptomatic school-going children in Lusaka, Zambia.
    Shadreck J Tembo; Mable M Mutengo; Lungowe Sitali; Katendi Changula; Ayato Takada; Aaron S Mweene; Edgar Simulundu; Simbarashe Chitanga
    Food and waterborne parasitology, 19, e00072, Jun. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Giardia duodenalis is one of the most common causes of diarrhea in humans with about 250-300 million cases per year. It is considered to be a species complex comprising of eight genetic assemblages (A to H), with assemblages A and B being the major causes of human infections. In this study we carried out genotypic characterization of G. duodenalis isolates detected in asymptomatic school-going children aged 3-16 years. Between May and September 2017, a total of 329 fecal samples were collected from school-going children from Chawama compound of Lusaka City and were screened for Giardia by microscopic examination. All microscopically positive fecal samples were analyzed by semi-nested polymerase chain reaction (PCR) targeting the glutamate dehydrogenase (gdh) gene. Genotyping of amplified PCR products was conducted by restriction fragment length polymorphism (RFLP) and DNA sequence analysis. Microscopically, Giardia was found in 10% (33/329) of fecal samples. The PCR-RFLP analysis of the gdh gene revealed assemblages A and B in 27.3% (9/33) and 72.7% (24/33), respectively. Furthermore, analysis with restriction enzymes identified sub-assemblages AII (27.3%, 9/33), BIII (12.1%, 4/33), BIV (51.5%, 17/33) and mixed infections of BIII and BIV (9.1%, 3/33). Phylogenetic analysis showed the clustering of 27.6% (8/29) and 72.4% (21/29) of Zambian Giardia gdh gene sequences into assemblages A and B, respectively. This study has revealed the presence of both assemblage A and B and that spread of G. duodenalis in school-going children appears to be mostly through anthroponotic transmission. To our knowledge, this is the first report of genotypic characterization of G. duodenalis identified in Zambia.
  • Potential Role of Nonneutralizing IgA Antibodies in Cross-Protective Immunity against Influenza A Viruses of Multiple Hemagglutinin Subtypes.
    Kosuke Okuya; Reiko Yoshida; Rashid Manzoor; Shinji Saito; Tadaki Suzuki; Michihito Sasaki; Takeshi Saito; Yurie Kida; Akina Mori-Kajihara; Tatsunari Kondoh; Masahiro Sato; Masahiro Kajihara; Hiroko Miyamoto; Osamu Ichii; Hideaki Higashi; Ayato Takada
    Journal of virology, 94, 12, 01 Jun. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, IgA antibodies on mucosal surfaces are known to play an important role in protection from influenza A virus (IAV) infection and are believed to be more potent than IgG for cross-protective immunity against IAVs of multiple hemagglutinin (HA) subtypes. However, in general, neutralizing antibodies specific to HA are principally HA subtype specific. Here, we focus on nonneutralizing but broadly cross-reactive HA-specific IgA antibodies. Recombinant IgG, monomeric IgA (mIgA), and polymeric secretory IgA (pSIgA) antibodies were generated based on the sequence of a mouse anti-HA monoclonal antibody (MAb) 5A5 that had no neutralizing activity but showed broad binding capacity to multiple HA subtypes. While confirming that there was no neutralizing activity of the recombinant MAbs against IAV strains A/Puerto Rico/8/1934 (H1N1), A/Adachi/2/1957 (H2N2), A/Hong Kong/483/1997 (H5N1), A/shearwater/South Australia/1/1972 (H6N5), A/duck/England/1/1956 (H11N6), and A/duck/Alberta/60/1976 (H12N5), we found that pSIgA, but not mIgA and IgG, significantly reduced budding and release of most of the viruses from infected cells. Electron microscopy demonstrated that pSIgA deposited newly produced virus particles on the surfaces of infected cells, most likely due to tethering of virus particles. Furthermore, we found that pSIgA showed significantly higher activity to reduce plaque sizes of the viruses than IgG and mIgA. These results suggest that nonneutralizing pSIgA reactive to multiple HA subtypes may play a role in intersubtype cross-protective immunity against IAVs.IMPORTANCE Mucosal immunity represented by pSIgA plays important roles in protection from IAV infection. Furthermore, IAV HA-specific pSIgA antibodies are thought to contribute to cross-protective immunity against multiple IAV subtypes. However, the mechanisms by which pSIgA exerts such versatile antiviral activity are not fully understood. In this study, we generated broadly cross-reactive recombinant IgG and pSIgA having the same antigen-recognition site and compared their antiviral activities in vitro These recombinant antibodies did not show "classical" neutralizing activity, whereas pSIgA, but not IgG, significantly inhibited the production of progeny virus particles from infected cells. Plaque formation was also significantly reduced by pSIgA, but not IgG. These effects were seen in infection with IAVs of several different HA subtypes. Based on our findings, we propose an antibody-mediated host defense mechanism by which mucosal immunity may contribute to broad cross-protection from IAVs of multiple HA subtypes, including viruses with pandemic potential.
  • West Nile Virus in Farmed Crocodiles, Zambia, 2019.
    Edgar Simulundu; Kunda Ndashe; Herman M Chambaro; David Squarre; Paul Michael Reilly; Simbarashe Chitanga; Katendi Changula; Andrew N Mukubesa; Joseph Ndebe; John Tembo; Nathan Kapata; Matthew Bates; Yona Sinkala; Bernard M Hang'ombe; King S Nalubamba; Masahiro Kajihara; Michihito Sasaki; Yasuko Orba; Ayato Takada; Hirofumi Sawa
    Emerging infectious diseases, 26, 4, 811, 814, Apr. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, We detected West Nile virus (WNV) nucleic acid in crocodiles (Crocodylus niloticus) in Zambia. Phylogenetically, the virus belonged to lineage 1a, which is predominant in the Northern Hemisphere. These data provide evidence that WNV is circulating in crocodiles in Africa and increases the risk for animal and human transmission.
  • エボラウイルスエンベロープへのホスファチジルセリン集積に関与する宿主スクランブラーゼの同定
    南保 明日香; 丸山 隼輝; 今井 正樹; 氏江 美智子; 高田 礼人; 大場 雄介; 河岡 義裕
    日本女性科学者の会学術誌, 20, 1, 65, 66, (一社)日本女性科学者の会, Mar. 2020
    Japanese
  • Genetic and Biological Diversity of Porcine Sapeloviruses Prevailing in Zambia.
    Hayato Harima; Masahiro Kajihara; Edgar Simulundu; Eugene Bwalya; Yongjin Qiu; Mao Isono; Kosuke Okuya; Gabriel Gonzalez; Junya Yamagishi; Bernard M Hang'ombe; Hirofumi Sawa; Aaron S Mweene; Ayato Takada
    Viruses, 12, 2, 05 Feb. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Porcine sapelovirus (PSV) has been detected worldwide in pig populations. Although PSV causes various symptoms such as encephalomyelitis, diarrhea, and pneumonia in pigs, the economic impact of PSV infection remains to be determined. However, information on the distribution and genetic diversity of PSV is quite limited, particularly in Africa. In this study, we investigated the prevalence of PSV infection in Zambia and characterized the isolated PSVs genetically and biologically. We screened 147 fecal samples collected in 2018 and found that the prevalences of PSV infection in suckling pigs and fattening pigs were high (36.2% and 94.0%, respectively). Phylogenetic analyses revealed that the Zambian PSVs were divided into three different lineages (Lineages 1-3) in the clade consisting of Chinese strains. The Zambian PSVs belonging to Lineages 2 and 3 replicated more efficiently than those belonging to Lineage 1 in Vero E6 and BHK cells. Bioinformatic analyses revealed that genetic recombination events had occurred and the recombination breakpoints were located in the L and 2A genes. Our results indicated that at least two biologically distinct PSVs could be circulating in the Zambian pig population and that genetic recombination played a role in the evolution of PSVs.
  • Detection of novel orthoreovirus genomes in shrew (Crocidura hirta) and fruit bat (Rousettus aegyptiacus).
    Hayato Harima; Michihito Sasaki; Masahiro Kajihara; Akina Mori-Kajihara; Bernard M Hang'ombe; Katendi Changula; Yasuko Orba; Hirohito Ogawa; Martin Simuunza; Reiko Yoshida; Aaron Mweene; Ayato Takada; Hirofumi Sawa
    The Journal of veterinary medical science, 82, 2, 162, 167, 04 Feb. 2020, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Orthoreoviruses have been indentified in several mammals, however, there is no information about orthoreoviruses in shrews. In this study, we screened wild animals in Zambia, including shrews, rodents, and bats for the detection of orthoreoviruses. Two orthoreovirus RNA genomes were detected from a shrew intestinal-contents (1/24) and a bat colon (1/96) sample by reverse-transcription (RT)-PCR targeting the RNA-dependent RNA polymerase gene of orthoreoviruses. Phylogenetic analyses revealed that each of the identified orthoreoviruses formed a distinct branch among members of the Orthoreovirus genus. This is the first report that shrews are susceptible to orthoreovirus infection. Our results suggest the existence of undiscovered orthoreoviruses in shrews and provide important information about the genetic diversity of orthoreoviruses.
  • Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism.
    Yoshihiro Takadate; Tatsunari Kondoh; Manabu Igarashi; Junki Maruyama; Rashid Manzoor; Hirohito Ogawa; Masahiro Kajihara; Wakako Furuyama; Masahiro Sato; Hiroko Miyamoto; Reiko Yoshida; Terence E Hill; Alexander N Freiberg; Heinz Feldmann; Andrea Marzi; Ayato Takada
    Cell reports, 30, 2, 308, 319, 14 Jan. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Fruit bats are suspected to be natural hosts of filoviruses, including Ebola virus (EBOV) and Marburg virus (MARV). Interestingly, however, previous studies suggest that these viruses have different tropisms depending on the bat species. Here, we show a molecular basis underlying the host-range restriction of filoviruses. We find that bat-derived cell lines FBKT1 and ZFBK13-76E show preferential susceptibility to EBOV and MARV, respectively, whereas the other bat cell lines tested are similarly infected with both viruses. In FBKT1 and ZFBK13-76E, unique amino acid (aa) sequences are found in the Niemann-Pick C1 (NPC1) protein, one of the cellular receptors interacting with the filovirus glycoprotein (GP). These aa residues, as well as a few aa differences between EBOV and MARV GPs, are crucial for the differential susceptibility to filoviruses. Taken together, our findings indicate that the heterogeneity of bat NPC1 orthologs is an important factor controlling filovirus species-specific host tropism.
  • Seroprevalence of Rift Valley fever in cattle of smallholder farmers in Kwilu Province in the Democratic Republic of Congo.
    Abdel-Amir Dib Halawi; Ngonda Saasa; Boniface Lombe Pongombo; Masahiro Kajihara; Herman Moses Chambaro; Mutambel Hity; Hirofumi Sawa; Ayato Takada; Aaron S Mweene; Luamba Lua Nsembo; Edgar Simulundu
    Tropical animal health and production, 51, 8, 2619, 2627, Nov. 2019, [International Magazine]
    English, Scientific journal, Rift Valley fever (RVF) is a zoonotic mosquito-borne disease caused by RVF virus (RVFV) that causes abortions and high mortalities in livestock and is also associated with acute and fatal disease in humans. In the Democratic Republic of Congo (DRC), information on the epidemiology of RVF is limited, particularly among cattle reared by smallholder farmers. This cross-sectional study was conducted to investigate the seroprevalence of RVF in cattle raised by smallholder farmers in Kwilu Province of DRC, which has not yet reported an RVF epidemic. A total of 677 cattle sera were collected from four territories and tested for anti-RVFV antibodies using immunofluorescent assay and enzyme-linked immunosorbent assay. The overall seroprevalence of anti-RVFV IgG was 6.5% (44/677) (95% CI 4.81-8.7). There was a statistically significant difference in the seroprevalence among the territories (χ2 = 28.79, p < 0.001). Territory seroprevalences were as follows: Idiofa 14.08% (95% CI 9.78-19.76), Bulungu 4.14% (95% CI 1.83-8.68), Gungu 3.21% (95% CI 1.41-6.78), and Masi-Manimba 1.19% (95% CI 0.06-7.37). Seroprevalence differed significantly among age categories (p = 0.0017) and ecosystem (p < 0.001). The seroprevalence of animals aged between 1 and 2 years was 20.0% (95% CI 8.4-39.13) and was higher than group aged <1 year, between 2 and 3 years, and > 3 years. Forest area (18.92% (95% CI 12.35-27.7)) had higher seropositivity than savannah area (4.06% (95% CI 2.65-6.12)). Sex difference was not significant (χ2 = 0.14, p = 0.704). These findings indicate that cattle in Kwilu Province had been exposed to RVFV, which represents a significant risk for both livestock and human health.
  • Molecular detection and characterization of genotype 1 bovine leukemia virus from beef cattle in the traditional sector in Zambia.
    Mundia M Phiri; Evans Kaimoyo; Katendi Changula; Isaac Silwamba; Herman M Chambaro; Penjaninge Kapila; Masahiro Kajihara; Martin Simuunza; John Bwalya Muma; Girja S Pandey; Ayato Takada; Aaron S Mweene; Simbarashe Chitanga; Edgar Simulundu
    Archives of virology, 164, 10, 2531, 2536, Oct. 2019, [International Magazine]
    English, Scientific journal, Whilst bovine leukemia virus (BLV) causes considerable economic losses to the dairy industry worldwide, information on its molecular epidemiology and economic impact in beef cattle is limited. Here, blood from 880 animals from Zambia's major cattle-rearing provinces was screened for BLV by nested PCR. Positive pools were sequenced and phylogenetically analyzed. The estimated pooled prevalence was 2.1%. All strains belonged to genotype 1 and formed a distinct phylogenetic cluster. The study suggests circulation of genotype 1 BLV in beef cattle in these regions. This is the first report on molecular detection and characterization of BLV from beef cattle in Africa.
  • Genetic diversity of rabies virus in different host species and geographic regions of Zambia and Zimbabwe.
    Muleya W; Chambaro HM; Sasaki M; Gwenhure LF; Mwenechanya R; Kajihara M; Saasa N; Mupila Z; Mori-Kajihara A; Qiu Y; Kangwa E; Mweene A; Namangala B; Takada A; Sawa H
    Virus genes, 55, 5, 713, 719, Oct. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Rabies is endemic in Zambia and Zimbabwe. The previously investigated strains of rabies virus in central Zambia belong to the Africa 1b lineage, with similar circulating virus strains found in the various tested hosts and regions. However, prior work assessed only limited regions and host species. Thus, this study aimed to more comprehensively determine the genetic diversity of rabies virus across regions of Zambia and Zimbabwe. RNA (n = 76) was extracted from positive direct fluorescent antibody test brain tissues from dog, cow, goat, cat, pig, human, and jackal collected from Zambia and Zimbabwe. The amplicons of the nucleoprotein and glycoprotein genes were obtained from all examined samples by nested RT-PCR and subsequently sequenced. A phylogenetic analysis of the N gene confirmed that all the endemic strains of rabies virus in Zambia and Zimbabwe belong to the Africa 1b lineage. The obtained viral gene sequences were phylogenetically divided into two clusters. Cluster II comprised only Zambian strains. In contrast, cluster I comprised both Zambia and Zimbabwe strains, with strains from Zimbabwe forming a distinct lineage from Zambian strains, implying viral genetic divergence due to geographical barriers. However, no evidence of clustering based on host or region was observed, implying the circulation of similar virus strains occurs in different hosts and regions of Zambia and Zimbabwe. The clustering of rabies virus strains from jackals with those from domestic animals provides evidence of similar virus strains circulating in both wildlife and domestic animals, and that the jackal might be one of the potential reservoirs of rabies virus infection. In this study, no strains circulating in Zimbabwe were detected in Zambia.
  • A versatile platform technology for recombinant vaccines using non-propagative human parainfluenza virus type 2 vector.
    Junpei Ohtsuka; Masayuki Fukumura; Wakako Furuyama; Shujie Wang; Kenichiro Hara; Mitsuyo Maeda; Masato Tsurudome; Hiroko Miyamoto; Aika Kaito; Nobuyuki Tsuda; Yosky Kataoka; Akira Mizoguchi; Ayato Takada; Tetsuya Nosaka
    Scientific reports, 9, 1, 12901, 12901, 09 Sep. 2019, [International Magazine]
    English, Scientific journal, Ectopic protein with proper steric structure was efficiently loaded onto the envelope of the F gene-defective BC-PIV vector derived from human parainfluenza virus type 2 (hPIV2) by a reverse genetics method of recombinant virus production. Further, ectopic antigenic peptide was successfully loaded either outside, inside, or at both sides of the envelope of the vector. The BC-PIV vector harboring the Ebola virus GP gene was able to elicit neutralizing antibodies in mice. In addition, BC-PIV with antigenic epitopes of both melanoma gp100 and WT1 tumor antigen induced a CD8+ T-cell-mediated response in tumor-transplanted syngeneic mice. Considering the low pathogenicity and recurrent infections of parental hPIV2, BC-PIV can be used as a versatile vector with high safety for recombinant vaccine development, addressing unmet medical needs.
  • 重症熱性血小板減少症候群ウイルスの核タンパク質Nと結合する宿主RNAの機能解明
    水間 奎太; 松野 啓太; 岡松 正敏; 高田 礼人; 迫田 義博
    日本獣医学会学術集会講演要旨集, 162回, 390, 390, (公社)日本獣医学会, Aug. 2019
    Japanese
  • マダニ中のフレボウイルスの遺伝子系統解析に基づく性状推定
    松野 啓太; 中尾 亮; 梶原 将大; 下田 宙; 海老原 秀喜; 高田 礼人; 前田 健; 岡松 正敏; 迫田 義博
    日本獣医学会学術集会講演要旨集, 162回, 400, 400, (公社)日本獣医学会, Aug. 2019
    Japanese
  • Marburgvirus in Egyptian Fruit Bats, Zambia.
    Masahiro Kajihara; Bernard M Hang'ombe; Katendi Changula; Hayato Harima; Mao Isono; Kosuke Okuya; Reiko Yoshida; Akina Mori-Kajihara; Yoshiki Eto; Yasuko Orba; Hirohito Ogawa; Yongjin Qiu; Hirofumi Sawa; Edgar Simulundu; Daniel Mwizabi; Musso Munyeme; David Squarre; Victor Mukonka; Aaron Mweene; Ayato Takada
    Emerging infectious diseases, 25, 8, 1577, 1580, Aug. 2019, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, We detected Marburg virus genome in Egyptian fruit bats (Rousettus aegyptiacus) captured in Zambia in September 2018. The virus was closely related phylogenetically to the viruses that previously caused Marburg outbreaks in the Democratic Republic of the Congo. This finding demonstrates that Zambia is at risk for Marburg virus disease.
  • Taxonomy of the order Mononegavirales: update 2019.
    Gaya K Amarasinghe; María A Ayllón; Yīmíng Bào; Christopher F Basler; Sina Bavari; Kim R Blasdell; Thomas Briese; Paul A Brown; Alexander Bukreyev; Anne Balkema-Buschmann; Ursula J Buchholz; Camila Chabi-Jesus; Kartik Chandran; Chiara Chiapponi; Ian Crozier; Rik L de Swart; Ralf G Dietzgen; Olga Dolnik; Jan F Drexler; Ralf Dürrwald; William G Dundon; W Paul Duprex; John M Dye; Andrew J Easton; Anthony R Fooks; Pierre B H Formenty; Ron A M Fouchier; Juliana Freitas-Astúa; Anthony Griffiths; Roger Hewson; Masayuki Horie; Timothy H Hyndman; Dàohóng Jiāng; Elliott W Kitajima; Gary P Kobinger; Hideki Kondō; Gael Kurath; Ivan V Kuzmin; Robert A Lamb; Antonio Lavazza; Benhur Lee; Davide Lelli; Eric M Leroy; Jiànróng Lǐ; Piet Maes; Shin-Yi L Marzano; Ana Moreno; Elke Mühlberger; Sergey V Netesov; Norbert Nowotny; Are Nylund; Arnfinn L Økland; Gustavo Palacios; Bernadett Pályi; Janusz T Pawęska; Susan L Payne; Alice Prosperi; Pedro Luis Ramos-González; Bertus K Rima; Paul Rota; Dennis Rubbenstroth; Mǎng Shī; Peter Simmonds; Sophie J Smither; Enrica Sozzi; Kirsten Spann; Mark D Stenglein; David M Stone; Ayato Takada; Robert B Tesh; Keizō Tomonaga; Noël Tordo; Jonathan S Towner; Bernadette van den Hoogen; Nikos Vasilakis; Victoria Wahl; Peter J Walker; Lin-Fa Wang; Anna E Whitfield; John V Williams; F Murilo Zerbini; Tāo Zhāng; Yong-Zhen Zhang; Jens H Kuhn
    Archives of virology, 164, 7, 1967, 1980, Jul. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, In February 2019, following the annual taxon ratification vote, the order Mononegavirales was amended by the addition of four new subfamilies and 12 new genera and the creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
  • Clinical Evaluation of QuickNaviTM-Ebola in the 2018 Outbreak of Ebola Virus Disease in the Democratic Republic of the Congo.
    Sheila Makiala; Daniel Mukadi; Anja De Weggheleire; Shino Muramatsu; Daisuke Kato; Koichi Inano; Fumio Gondaira; Masahiro Kajihara; Reiko Yoshida; Katendi Changula; Aaron Mweene; Placide Mbala-Kingebeni; Jean-Jacques Muyembe-Tamfum; Justin Masumu; Steve Ahuka; Ayato Takada
    Viruses, 11, 7, 28 Jun. 2019, [International Magazine]
    English, Scientific journal, The recent large outbreaks of Ebola virus disease (EVD) in West Africa and the Democratic Republic of the Congo (DRC) have highlighted the need for rapid diagnostic tests to control this disease. In this study, we clinically evaluated a previously developed immunochromatography-based kit, QuickNaviTM-Ebola. During the 2018 outbreaks in DRC, 928 blood samples from EVD-suspected cases were tested with QuickNaviTM-Ebola and the WHO-approved GeneXpert. The sensitivity and specificity of QuickNaviTM-Ebola, estimated by comparing it to GeneXpert-confirmed cases, were 85% (68/80) and 99.8% (846/848), respectively. These results indicate the practical reliability of QuickNaviTM-Ebola for point-of-care diagnosis of EVD.
  • Human Borreliosis Caused by a New World Relapsing Fever Borrelia-like Organism in the Old World.
    Yongjin Qiu; Ryo Nakao; Bernard Mudenda Hang'ombe; Kozue Sato; Masahiro Kajihara; Sharon Kanchela; Katendi Changula; Yoshiki Eto; Joseph Ndebe; Michihito Sasaki; May June Thu; Ayato Takada; Hirohumi Sawa; Chihiro Sugimoto; Hiroki Kawabata
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 69, 1, 107, 112, 18 Jun. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Relapsing fever is an infectious disease previously neglected in Africa, which imposes a large public health burden in the country. We aimed to investigate and report on a case of relapsing fever borreliosis in Zambia. METHODS: A previously unknown Borrelia species was isolated from the blood of a febrile patient. Investigations of the presumptive vector ticks and natural hosts for the Borrelia species were conducted by culture isolation and/or DNA detection by Borrelia-specific polymerase chain reaction. Using culture isolates from the patient and bat specimens, genetic characterization was performed by multilocus sequence analysis based on the draft genome sequences. RESULTS: The febrile patient was diagnosed with relapsing fever. The isolated Borrelia species was frequently detected in Ornithodoros faini (n = 20/50 [40%]) and bats (n = 64/237 [27%]). Multilocus sequence analysis based on a draft genome sequence revealed that the Borrelia species isolates from the patient and presumptive reservoir host (bats) formed a monophyletic lineage that clustered with relapsing fever borreliae found in the United States. CONCLUSIONS: A febrile illness caused by a Borrelia species that was treatable with erythromycin was identified in Zambia. This is the first study to report on relapsing fever Borrelia in Zambia and suggesting the likely natural reservoir hosts of the isolated Borrelia species. Interestingly, the isolated Borrelia species was more closely related to New World relapsing fever borreliae, despite being detected in the Afrotropic ecozone.
  • ICTV Virus Taxonomy Profile: Filoviridae.
    Kuhn JH; Amarasinghe GK; Basler CF; Bavari S; Bukreyev A; Chandran K; Crozier I; Dolnik O; Dye JM; Formenty PBH; Griffiths A; Hewson R; Kobinger GP; Leroy EM; Mühlberger E; Netesov Нетёсов Сергей Викторович SV; Palacios G; Pályi B; Pawęska JT; Smither SJ; Takada 高田礼人; Towner JS; Wahl V; Ictv Report; Consortium
    The Journal of general virology, 100, 6, 911, 912, Jun. 2019, [Peer-reviewed]
    English, Scientific journal
  • Molecular characterization and phylogenetic analysis of Trypanosoma spp. isolated from striped leaf-nosed bat (Hipposideros vittatus) in Zambia.
    Qiu Y; Simuunza M; Mwizabi D; Changula K; Harima H; Takada A; Kajihara M; Takadate Y; Nakao R; Kawabata H; Sugimoto C; Mweene A; Sawa H; Eto Y; Mudenda Hang’ombe B; Hayashida K; Yoshida R; Mori-Kajihara A; Ndebe J
    International Journal for Parasitology, 9, 234, 238, Apr. 2019, [Peer-reviewed]
    English, Scientific journal
  • Taxonomy of the order Mononegavirales: second update 2018.
    Piet Maes; Gaya K Amarasinghe; María A Ayllón; Christopher F Basler; Sina Bavari; Kim R Blasdell; Thomas Briese; Paul A Brown; Alexander Bukreyev; Anne Balkema-Buschmann; Ursula J Buchholz; Kartik Chandran; Ian Crozier; Rik L de Swart; Ralf G Dietzgen; Olga Dolnik; Leslie L Domier; Jan F Drexler; Ralf Dürrwald; William G Dundon; W Paul Duprex; John M Dye; Andrew J Easton; Anthony R Fooks; Pierre B H Formenty; Ron A M Fouchier; Juliana Freitas-Astúa; Elodie Ghedin; Anthony Griffiths; Roger Hewson; Masayuki Horie; Julia L Hurwitz; Timothy H Hyndman; Dàohóng Jiāng; Gary P Kobinger; Hideki Kondō; Gael Kurath; Ivan V Kuzmin; Robert A Lamb; Benhur Lee; Eric M Leroy; Jiànróng Lǐ; Shin-Yi L Marzano; Elke Mühlberger; Sergey V Netesov; Norbert Nowotny; Gustavo Palacios; Bernadett Pályi; Janusz T Pawęska; Susan L Payne; Bertus K Rima; Paul Rota; Dennis Rubbenstroth; Peter Simmonds; Sophie J Smither; Qisheng Song; Timothy Song; Kirsten Spann; Mark D Stenglein; David M Stone; Ayato Takada; Robert B Tesh; Keizō Tomonaga; Noël Tordo; Jonathan S Towner; Bernadette van den Hoogen; Nikos Vasilakis; Victoria Wahl; Peter J Walker; David Wang; Lin-Fa Wang; Anna E Whitfield; John V Williams; Gōngyín Yè; F Murilo Zerbini; Yong-Zhen Zhang; Jens H Kuhn
    Archives of virology, 164, 4, 1233, 1244, Apr. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, In October 2018, the order Mononegavirales was amended by the establishment of three new families and three new genera, abolishment of two genera, and creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
  • Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans.
    Rijal P; Elias SC; Machado SR; Xiao J; Schimanski L; O'Dowd V; Baker T; Barry E; Mendelsohn SC; Cherry CJ; Jin J; Labbé GM; Donnellan FR; Rampling T; Dowall S; Rayner E; Findlay-Wilson S; Carroll M; Guo J; Xu XN; Huang KA; Takada A; Burgess G; McMillan D; Popplewell A; Lightwood DJ; Draper SJ; Townsend AR
    Cell reports, 27, 1, 172, 186.e7, Apr. 2019, [Peer-reviewed]
    English, Scientific journal
  • Diversity of spotted fever group rickettsiae and their association with host ticks in Japan.
    May June Thu; Yongjin Qiu; Keita Matsuno; Masahiro Kajihara; Akina Mori-Kajihara; Ryosuke Omori; Naota Monma; Kazuki Chiba; Junji Seto; Mutsuyo Gokuden; Masako Andoh; Hideo Oosako; Ken Katakura; Ayato Takada; Chihiro Sugimoto; Norikazu Isoda; Ryo Nakao
    Scientific reports, 9, 1, 1500, 1500, 06 Feb. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Spotted fever group (SFG) rickettsiae are obligate intracellular Gram-negative bacteria mainly associated with ticks. In Japan, several hundred cases of Japanese spotted fever, caused by Rickettsia japonica, are reported annually. Other Rickettsia species are also known to exist in ixodid ticks; however, their phylogenetic position and pathogenic potential are poorly understood. We conducted a nationwide cross-sectional survey on questing ticks to understand the overall diversity of SFG rickettsiae in Japan. Out of 2,189 individuals (19 tick species in 4 genera), 373 (17.0%) samples were positive for Rickettsia spp. as ascertained by real-time PCR amplification of the citrate synthase gene (gltA). Conventional PCR and sequencing analyses of gltA indicated the presence of 15 different genotypes of SFG rickettsiae. Based on the analysis of five additional genes, we characterised five Rickettsia species; R. asiatica, R. helvetica, R. monacensis (formerly reported as Rickettsia sp. In56 in Japan), R. tamurae, and Candidatus R. tarasevichiae and several unclassified SFG rickettsiae. We also found a strong association between rickettsial genotypes and their host tick species, while there was little association between rickettsial genotypes and their geographical origins. These observations suggested that most of the SFG rickettsiae have a limited host range and are maintained in certain tick species in the natural environment.
  • Generation of bat-derived influenza viruses and their reassortants.
    Masahiro Sato; Junki Maruyama; Tatsunari Kondoh; Naganori Nao; Hiroko Miyamoto; Yoshihiro Takadate; Wakako Furuyama; Masahiro Kajihara; Hirohito Ogawa; Rashid Manzoor; Reiko Yoshida; Manabu Igarashi; Ayato Takada
    Scientific reports, 9, 1, 1158, 1158, 04 Feb. 2019, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Two novel influenza A virus-like genomes were detected in fruit bats in Central and South America. However, the biological properties of these bat-derived influenza viruses (BatIVs) are still largely unknown since infectious viral particles have never been isolated from the infected host species. In this study, a reverse genetics approach was used to generate infectious BatIV particles entirely from plasmids encoding full-length sequences in eight gene segments. We inoculated BatIV particles into various cell cultures including bat-derived cell lines and found that BatIVs infected particular bat-derived cells efficiently but not the other cell lines tested. Reassortant viruses between the two BatIVs were also successfully generated and their replication in the susceptible bat cell lines was confirmed. These findings suggest a limited host range and reassortment potential of BatIVs in nature, providing fundamental information for understanding of the ecology of BatIVs.
  • Infection of newly identified phleboviruses in ticks and wild animals in Hokkaido, Japan indicating tick-borne life cycles.
    Shiho Torii; Keita Matsuno; Yongjin Qiu; Akina Mori-Kajihara; Masahiro Kajihara; Ryo Nakao; Naganori Nao; Katsunori Okazaki; Mariko Sashika; Takahiro Hiono; Masatoshi Okamatsu; Yoshihiro Sakoda; Hideki Ebihara; Ayato Takada; Hirofumi Sawa
    Ticks and tick-borne diseases, 10, 2, 328, 335, Feb. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Recent discoveries of tick-borne pathogens have raised public health concerns on tick-borne infectious diseases and emphasize the need to assess potential risks of unrecognized tick-borne pathogens. First, to determine the existence of tick-borne phleboviruses (TBPVs), genetic surveillance of phleboviruses in ticks was conducted mainly in Hokkaido, the northernmost island in Japan from 2013 to 2015. Genes of two TBPVs, previously reported as Mukawa virus (MKWV) and a newly identified relative of MKWV, Kuriyama virus (KURV), were detected and the viruses were isolated from Ixodes persulcatus collected in Hokkaido, but not in I. persulcatus collected from other areas of Japan. These viruses were phylogenetically and antigenically similar to each other. Next, to investigate the infection of MKWV in mammals, serum samples from wildlife captured in Hokkaido from 2007 to 2011 were used for serological screening. Neutralizing antibodies against MKWV were detected in both Yezo-deer (Cervus nippon yesoensis) (2/50) and raccoons (Procyon lotor) (16/64). However, no infectious MKWV was recovered from laboratory mice in experimental infections, though viral RNAs were detected in their tissues. Thus, MKWV and KURV may maintain tick-mammalian life cycles in Hokkaido, suggesting their potential as causative agents of tick-borne diseases in mammals.
  • First genetic detection and characterization of canine parvovirus from diarrheic dogs in Zambia.
    Kapiya J; Nalubamba KS; Kaimoyo E; Changula K; Chidumayo N; Saasa N; Simuunza MC; Takada A; Mweene AS; Chitanga S; Simulundu E
    Archives of virology, 164, 1, 303, 307, Jan. 2019, [Peer-reviewed]
    English, Scientific journal
  • Characterization of a novel species of adenovirus from Japanese microbat and role of CXADR as its entry factor.
    Kobayashi T; Matsugo H; Maruyama J; Kamiki H; Takada A; Maeda K; Takenaka-Uema A; Tohya Y; Murakami S; Horimoto T
    Scientific reports, 9, 1, 573, 573, Jan. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Recently, bat adenoviruses (BtAdVs) of genus Mastadenovirus have been isolated from various bat species, some of them displaying a wide host range in cell culture. In this study, we isolated two BtAdVs from Japanese wild microbats. While one isolate was classified as Bat mastadenovirus A, the other was phylogenetically independent of other BtAdVs. It was rather related to, but serologically different from, canine adenoviruses. We propose that the latter, isolated from Asian parti-colored bat, should be assigned to a novel species of Bat mastadenovirus. Both isolates replicated in various mammalian cell lines, implying their wide cell tropism. To gain insight into cell tropism of these BtAdVs, we investigated the coxsackievirus and adenovirus receptor (CXADR) for virus entry to the cells. We prepared CXADR-knockout canine kidney cells and found that replication of BtAdVs was significantly hampered in these cells. For confirmation, their replication in canine CXADR-addback cells was rescued to the levels with the original cells. We also found that viral replication was corrected in human or bat CXADR-transduced cells to similar levels as in canine CXADR-addback cells. These results suggest that BtAdVs were able to use several mammalian-derived CXADRs as entry factors.
  • A Critical Domain of Ebolavirus Envelope Glycoprotein Determines Glycoform and Infectivity
    Haruhiko Fujihira; Katsuaki Usami; Keita Matsuno; Hideyuki Takeuchi; Kaori Denda-Nagai; Jun-Ichi Furukawa; Yasuro Shinohara; Ayato Takada; Yoshihiro Kawaoka; Tatsuro Irimura
    Scientific Reports, 8, 1, 5495, Nature Publishing Group, 01 Dec. 2018, [Peer-reviewed]
    English, Scientific journal
  • Seroprevalence of Filovirus Infection of Rousettus aegyptiacus Bats in Zambia.
    Katendi Changula; Masahiro Kajihara; Akina Mori-Kajihara; Yoshiki Eto; Hiroko Miyamoto; Reiko Yoshida; Asako Shigeno; Bernard Hang'ombe; Yongjin Qiu; Daniel Mwizabi; David Squarre; Joseph Ndebe; Hirohito Ogawa; Hayato Harima; Edgar Simulundu; Ladslav Moonga; Penjaninge Kapila; Wakako Furuyama; Tatsunari Kondoh; Masahiro Sato; Yoshihiro Takadate; Chiho Kaneko; Ryo Nakao; Victor Mukonka; Aaron Mweene; Ayato Takada
    The Journal of infectious diseases, 218, suppl_5, S312-S317, S317, 22 Nov. 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Bats are suspected to play important roles in the ecology of filoviruses, including ebolaviruses and marburgviruses. A cave-dwelling fruit bat, Rousettus aegyptiacus, has been shown to be a reservoir of marburgviruses. Using an enzyme-linked immunosorbent assay with the viral glycoprotein antigen, we detected immunoglobulin G antibodies specific to multiple filoviruses in 158 of 290 serum samples of R aegyptiacus bats captured in Zambia during the years 2014-2017. In particular, 43.8% of the bats were seropositive to marburgvirus, supporting the notion that this bat species continuously maintains marburgviruses as a reservoir. Of note, distinct peaks of seropositive rates were repeatedly observed at the beginning of rainy seasons, suggesting seasonality of the presence of newly infected individuals in this bat population. These data highlight the need for continued monitoring of filovirus infection in this bat species even in countries where filovirus diseases have not been reported.
  • Single-Nucleotide Polymorphisms in Human NPC1 Influence Filovirus Entry Into Cells.
    Tatsunari Kondoh; Michael Letko; Vincent J Munster; Rashid Manzoor; Junki Maruyama; Wakako Furuyama; Hiroko Miyamoto; Asako Shigeno; Daisuke Fujikura; Yoshihiro Takadate; Reiko Yoshida; Manabu Igarashi; Heinz Feldmann; Andrea Marzi; Ayato Takada
    The Journal of infectious diseases, 218, suppl_5, S397-S402, S402, 22 Nov. 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Niemann-Pick C1 (NPC1), a host receptor involved in the envelope glycoprotein (GP)-mediated entry of filoviruses into cells, is believed to be a major determinant of cell susceptibility to filovirus infection. It is known that proteolytically digested Ebola virus (EBOV) GP interacts with 2 protruding loops in domain C of NPC1. Using previously published structural data and the National Center for Biotechnology Information Single-Nucleotide Polymorphism (SNP) database, we identified 10 naturally occurring missense SNPs in human NPC1. To investigate whether these SNPs affect cell susceptibility to filovirus infection, we generated Vero E6 cell lines stably expressing NPC1 with SNP substitutions and compared their susceptibility to vesicular stomatitis virus pseudotyped with filovirus GPs and infectious EBOV. We found that some of the substitutions resulted in reduced susceptibility to filoviruses, as indicated by the lower titers and smaller plaque/focus sizes of the viruses. Our data suggest that human NPC1 SNPs may likely affect host susceptibility to filoviruses.
  • Two Conserved Amino Acids within the NSs of Severe Fever with Thrombocytopenia Syndrome Phlebovirus Are Essential for Anti-interferon Activity.
    Moriyama M; Igarashi M; Koshiba T; Irie T; Takada A; Ichinohe T
    Journal of virology, 92, 19, Oct. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) sequesters TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures to inhibit the phosphorylation and nuclear translocation of interferon (IFN) regulatory factor 3 (IRF3) and subsequent interferon beta (IFN-β) production. Although the C-terminal region of SFTSV NSs (NSs66-249) has been linked to the formation of NSs-induced cytoplasmic structures and inhibition of host IFN-β responses, the role of the N-terminal region in antagonizing host antiviral responses remains to be defined. Here, we demonstrate that two conserved amino acids at positions 21 and 23 in the SFTSV and heartland virus (HRTV) NSs are essential for suppression of IRF3 phosphorylation and IFN-β mRNA expression following infection with SFTSV or recombinant influenza virus lacking the NS1 gene. Surprisingly, formation of SFTSV/HRTV NSs-induced cytoplasmic structures is not essential for inhibition of host antiviral responses. Rather, an association between SFTSV/HRTV NSs and TBK1 is required for suppression of mitochondrial antiviral signaling protein (MAVS)-mediated activation of IFN-β promoter activity. Although SFTSV NSs did not prevent the ubiquitination of TBK1, it associates with TBK1 through its N-terminal kinase domain (residues 1 to 307) to block the autophosphorylation of TBK1. Furthermore, we found that both wild-type NSs and the 21/23A mutant (NSs in which residues at positions 21 and 23 were replaced with alanine) of SFTSV suppressed NLRP3 inflammasome-dependent interleukin-1β (IL-1β) secretion, suggesting that the importance of these residues is restricted to TBK1-dependent IFN signaling. Together, our findings strongly implicate the two conserved amino acids at positions 21 and 23 of SFTSV/HRTV NSs in the inhibition of host interferon responses.IMPORTANCE Recognition of viruses by host innate immune systems plays a critical role not only in providing resistance to viral infection but also in the initiation of antigen-specific adaptive immune responses against viruses. Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by the SFTS phlebovirus (SFTSV), a highly pathogenic tick-borne phlebovirus. The 294-amino-acid nonstructural protein (NSs) of SFTSV associates with TANK-binding kinase 1 (TBK1), a key regulator of host innate antiviral immunity, to inhibit interferon beta (IFN-β) production and enhance viral replication. Here, we demonstrate that two conserved amino acids at positions 21 and 23 in the NSs of SFTSV and heartland virus, another tick-borne phlebovirus, are essential for association with TBK1 and suppression of IFN-β production. Our results provide important insight into the molecular mechanisms by which SFTSV NSs helps to counteract host antiviral strategies.
  • Identification of group A rotaviruses from Zambian fruit bats provides evidence for long-distance dispersal events in Africa
    Michihito Sasaki; Masahiro Kajihara; Katendi Changula; Akina Mori-Kajihara; Hirohito Ogawa; Bernard M. Hang'ombe; Aaron S. Mweene; Martin Simuunza; Reiko Yoshida; Michael Carr; Yasuko Orba; Ayato Takada; Hirofumi Sawa
    Infection, Genetics and Evolution, 63, 104, 109, Elsevier B.V., 01 Sep. 2018, [Peer-reviewed]
    English, Scientific journal
  • Fatal Tickborne Phlebovirus Infection in Captive Cheetahs, Japan.
    Keita Matsuno; Noriyuki Nonoue; Ayako Noda; Nodoka Kasajima; Keita Noguchi; Ai Takano; Hiroshi Shimoda; Yasuko Orba; Mieko Muramatsu; Yoshihiro Sakoda; Ayato Takada; Shinji Minami; Yumi Une; Shigeru Morikawa; Ken Maeda
    Emerging infectious diseases, 24, 9, 1726, 1729, Sep. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Two captive cheetahs from a zoo in Japan died of a severe fever with thrombocytopenia syndrome-like illness. Severe fever with thrombocytopenia syndrome virus, an endemic tickborne phlebovirus, was detected systemically with secretion of infectious viruses into the saliva. These cases highlight the risk for exposure of captive animals to endemic arthropodborne pathogens.
  • Structural Characterization of Pan-ebolavirus Antibody 6D6 Targeting the Fusion Peptide of the Surface Glycoprotein.
    Milligan JC; Parekh DV; Fuller KM; Igarashi M; Takada A; Saphire EO
    The Journal of infectious diseases, 219, 3, 415, 419, Sep. 2018, [Peer-reviewed]
    English, Scientific journal
  • Taxonomy of the order Mononegavirales: update 2018.
    Gaya K Amarasinghe; Nidia G Aréchiga Ceballos; Ashley C Banyard; Christopher F Basler; Sina Bavari; Andrew J Bennett; Kim R Blasdell; Thomas Briese; Alexander Bukreyev; Yíngyún Caì; Charles H Calisher; Cristine Campos Lawson; Kartik Chandran; Colin A Chapman; Charles Y Chiu; Kang-Seuk Choi; Peter L Collins; Ralf G Dietzgen; Valerian V Dolja; Olga Dolnik; Leslie L Domier; Ralf Dürrwald; John M Dye; Andrew J Easton; Hideki Ebihara; Juan E Echevarría; Anthony R Fooks; Pierre B H Formenty; Ron A M Fouchier; Conrad M Freuling; Elodie Ghedin; Tony L Goldberg; Roger Hewson; Masayuki Horie; Timothy H Hyndman; Dàohóng Jiāng; Robert Kityo; Gary P Kobinger; Hideki Kondō; Eugene V Koonin; Mart Krupovic; Gael Kurath; Robert A Lamb; Benhur Lee; Eric M Leroy; Piet Maes; Andrea Maisner; Denise A Marston; Sunil Kumar Mor; Thomas Müller; Elke Mühlberger; Víctor Manuel Neira Ramírez; Sergey V Netesov; Terry Fei Fan Ng; Norbert Nowotny; Gustavo Palacios; Jean L Patterson; Janusz T Pawęska; Susan L Payne; Karla Prieto; Bertus K Rima; Paul Rota; Dennis Rubbenstroth; Martin Schwemmle; Stuart Siddell; Sophie J Smither; Qisheng Song; Timothy Song; Mark D Stenglein; David M Stone; Ayato Takada; Robert B Tesh; Luciano Matsumiya Thomazelli; Keizō Tomonaga; Noël Tordo; Jonathan S Towner; Nikos Vasilakis; Sonia Vázquez-Morón; Claudio Verdugo; Viktor E Volchkov; Victoria Wahl; Peter J Walker; David Wang; Lin-Fa Wang; James F X Wellehan; Michael R Wiley; Anna E Whitfield; Yuri I Wolf; Gōngyín Yè; Yǒng-Zhèn Zhāng; Jens H Kuhn
    Archives of virology, 163, 8, 2283, 2294, Aug. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, In 2018, the order Mononegavirales was expanded by inclusion of 1 new genus and 12 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.
  • Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection.
    Saphire EO; Schendel SL; Fusco ML; Gangavarapu K; Gunn BM; Wec AZ; Halfmann PJ; Brannan JM; Herbert AS; Qiu X; Wagh K; He S; Giorgi EE; Theiler J; Pommert KBJ; Krause TB; Turner HL; Murin CD; Pallesen J; Davidson E; Ahmed R; Aman MJ; Bukreyev A; Burton DR; Crowe JE Jr; Davis CW; Georgiou G; Krammer F; Kyratsous CA; Lai JR; Nykiforuk C; Pauly MH; Rijal P; Takada A; Townsend AR; Volchkov V; Walker LM; Wang CI; Zeitlin L; Doranz BJ; Ward AB; Korber B; Kobinger GP; Andersen KG; Kawaoka Y; Alter G; Chandran K; Dye JM; Viral Hemorrhagic Fever; Immunotherapeutic Consortium
    Cell, 174, 4, 938, 952.e13, Aug. 2018, [Peer-reviewed]
    English, Scientific journal
  • The Unique Phylogenetic Position of a Novel Tick-Borne Phlebovirus Ensures an Ixodid Origin of the Genus Phlebovirus.
    Keita Matsuno; Masahiro Kajihara; Ryo Nakao; Naganori Nao; Akina Mori-Kajihara; Mieko Muramatsu; Yongjin Qiu; Shiho Torii; Manabu Igarashi; Nodoka Kasajima; Keita Mizuma; Kentaro Yoshii; Hirofumi Sawa; Chihiro Sugimoto; Ayato Takada; Hideki Ebihara
    mSphere, 3, 3, 27 Jun. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The recent emergence of novel tick-borne RNA viruses has complicated the epidemiological landscape of tick-borne infectious diseases, posing a significant challenge to public health systems that seek to counteract tick-borne diseases. The identification of two novel tick-borne phleboviruses (TBPVs), severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV), as causative agents of severe illness in humans has accelerated the investigation and discoveries of novel TBPVs. In the present study, we isolated a novel TBPV designated Mukawa virus (MKWV) from host-questing Ixodes persulcatus females captured in Japan. Genetic characterization revealed that MKWV is a member of the genus Phlebovirus in the family Phenuiviridae Interestingly, MKWV is genetically distinct from other known TBPVs and shares a most recent common ancestor with mosquito/sandfly-borne (insect-borne) phleboviruses. Despite its genetic similarity to insect-borne phleboviruses, the molecular footprints of its viral proteins and its biological characteristics define MKWV as a tick-borne virus that can be transmitted to mammals. A phylogenetic ancestral-state reconstruction for arthropod vectors of phleboviruses including MKWV based on viral L segment sequences indicated that ticks likely harbored ancestral phleboviruses that evolved into both the tick-borne and MKWV/insect-borne phlebovirus lineages. Overall, our findings suggest that most of the phlebovirus evolution has occurred in hard ticks to generate divergent viruses, which may provide a seminal foundation for understanding the mechanisms underlying the evolution and emergence of pathogenic phleboviruses, such as Rift Valley fever virus and SFTSV/HRTV.IMPORTANCE The emergence of novel tick-borne RNA viruses causing severe illness in humans has complicated the epidemiological landscape of tick-borne diseases, requiring further investigation to safeguard public health. In the present study, we discovered a novel tick-borne phlebovirus from Ixodes persulcatus ticks in Japan. While its viral RNA genome sequences were similar to those of mosquito/sandfly-borne viruses, molecular and biological footprints confirmed that this is a tick-borne virus. The unique evolutionary position of the virus allowed us to estimate the ancestral phlebovirus vector, which was likely a hard tick. Our findings may provide a better understanding of the evolution and emergence of phleboviruses associated with emerging infectious diseases, such as severe fever with thrombocytopenia syndrome (SFTS) and Heartland virus disease.
  • Monoclonal Antibody Cocktail Protects Hamsters From Lethal Marburg Virus Infection.
    Marzi A; Haddock E; Kajihara M; Feldmann H; Takada A
    The Journal of infectious diseases, 218, suppl_5, S662, S665, Jun. 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Marburg virus (MARV), family Filoviridae, causes Marburg hemorrhagic fever (MHF) in humans and nonhuman primates with case fatality rates of up to 90%. There is no approved therapeutic for MHF, yet several experimental approaches have been evaluated in preclinical studies including small interfering RNA and monoclonal antibody (mAb) treatment. In this study we attempted to improve the therapeutic efficacy of the neutralizing mAb M4 by combining treatment with 1 or 2 of blocking but nonneutralizing mAbs 126-15 and 127-8. We found that single-dose treatment early after infection with the neutralizing mAb M4 or any of the mAb combinations resulted in similar protection in the MARV hamster model. However, a single-dose treatment with the cocktail of all 3 mAbs provided the best protection in delayed treatment, with 67%-100% of the animals surviving a lethal challenge depending on the time of treatment. This study identified a new promising mAb cocktail as a therapeutic option for MHF.
  • Genetic characterisation of African swine fever virus from 2017 outbreaks in Zambia: Identification of p72 genotype II variants in domestic pigs.
    Simulundu E; Sinkala Y; Chambaro HM; Chinyemba A; Banda F; Mooya LE; Ndebe J; Chitanga S; Makungu C; Munthali G; Fandamu P; Takada A; Mweene AS
    The Onderstepoort journal of veterinary research, 85, 1, e1, e5, Jun. 2018, [Peer-reviewed]
    English, Scientific journal
  • Characterization of field infectious bursal disease viruses in Zambia: evidence of co-circulation of multiple genotypes with predominance of very virulent strains
    Racheal Mwenda; Katendi Changula; Bernard M. Hang’ombe; Nozyechi Chidumayo; Alfred S. Mangani; Titus Kaira; Ayato Takada; Aaron S. Mweene; Edgar Simulundu
    Avian Pathology, 47, 3, 300, 313, Taylor and Francis Ltd., 04 May 2018, [Peer-reviewed]
    English, Scientific journal
  • The Role of Heparan Sulfate Proteoglycans as an Attachment Factor for Rabies Virus Entry and Infection.
    Sasaki M; Anindita PD; Ito N; Sugiyama M; Carr M; Fukuhara H; Ose T; Maenaka K; Takada A; Hall WW; Orba Y; Sawa H
    The Journal of infectious diseases, 217, 11, 1740, 1749, May 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Rabies virus (RABV) is the causative agent of fatal neurological disease. Cellular attachment is the initial and essential step for viral infections. Although extensive studies have demonstrated that RABV uses various target cell molecules to mediate infection, no specific molecule has been identified as an attachment factor for RABV infection. Here we demonstrate that cellular heparan sulfate (HS) supports RABV adhesion and subsequent entry into target cells. Enzymatic removal of HS reduced cellular susceptibility to RABV infection, and heparin, a highly sulfated form of HS, blocked viral adhesion and infection. The direct binding between RABV glycoprotein and heparin was demonstrated, and this interaction was shown to require HS N- and 6-O-sulfation. We also revealed that basic amino acids in the ectodomain of RABV glycoprotein serve as major determinants for the RABV-HS interaction. Collectively, our study highlights a previously undescribed role of HS as an attachment factor for RABV infection.
  • Tick-borne haemoparasites and Anaplasmataceae in domestic dogs in Zambia.
    Yongjin Qiu; Chiho Kaneko; Masahiro Kajihara; Saasa Ngonda; Edgar Simulundu; Walter Muleya; May June Thu; Mudenda Bernard Hang'ombe; Ken Katakura; Ayato Takada; Hirofumi Sawa; Martin Simuunza; Ryo Nakao
    Ticks and tick-borne diseases, 9, 4, 988, 995, May 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Tick-borne diseases (TBDs), including emerging and re-emerging infectious diseases, are important threats to human and animal health worldwide. Indeed, the number of reported human and animal infectious cases of novel TBD agents has increased in recent decades. However, TBDs tend to be neglected, especially in resource-limited countries that often have limited diagnostic capacity. The aim of this molecular survey was to detect and characterise tick-borne pathogens (Babesia, Theileria, and Hepatozoon parasites and Anaplasmataceae bacteria) in domestic dogs in Zambia. In total, 247 canine peripheral blood samples were collected in Lusaka, Mazabuka, Monze, and Shangombo. Conventional PCR to detect the selected pathogens was performed using DNA extracted from canine blood. One hundred eleven samples were positive for protozoa and 5 were positive for Anaplasmataceae. Sequencing of thirty-five randomly selected protozoa-positive samples revealed the presence of Babesia rossi, Babesia vogeli, and Hepatozoon canis 18S rDNA. Based on these sequences, a multiplex PCR system was developed to yield PCR products with different amplicons, the size of which depended on the parasite species; thus, each species could be identified without the need for sequence analysis. Approximately 40% of dogs were positive for H. canis. In particular, the positive rate (75.2%) of H. canis infection was significantly higher in Shangombo than in other sampling sites. Multiplex PCR assay detected B. rossi and B. vogeli infections in five and seven dogs, respectively, indicating that this approach is useful for detecting parasites with low prevalence. Sequencing analysis of gltA and groEL genes of Anaplasmataceae revealed that two and one dogs in Lusaka were infected with Anaplasma platys and Ehrlichia canis, respectively. The data indicated that Zambian dogs were infected with multiple tick-borne pathogens such as H. canis, B. rossi, B. vogeli, A. platys, E. canis and uncharacterized Ehrlichia sp. Since some of these parasites are zoonotic, concerted efforts are needed to raise awareness of, and control, these tick-borne pathogens.
  • Expression of a Recombinant Nucleocapsid Protein of Rift Valley Fever Virus in Vero Cells as an Immunofluorescence Antigen and Its Use for Serosurveillance in Traditional Cattle Herds in Zambia
    Ngonda Saasa; Masahiro Kajihara; George Dautu; Akina Mori-Kajihara; Shuetsu Fukushi; Yona Sinkala; Shigeru Morikawa; Aaron Mweene; Ayato Takada; Kumiko Yoshimatsu; Jiro Arikawa
    Vector-Borne and Zoonotic Diseases, 18, 5, 273, 277, Mary Ann Liebert Inc., 01 May 2018, [Peer-reviewed]
    English, Scientific journal
  • Co-circulation of multiple genotypes of African swine fever viruses among domestic pigs in Zambia (2013-2015).
    Simulundu E; Chambaro HM; Sinkala Y; Kajihara M; Ogawa H; Mori A; Ndebe J; Dautu G; Mataa L; Lubaba CH; Simuntala C; Fandamu P; Simuunza M; Pandey GS; Samui KL; Misinzo G; Takada A; Mweene AS
    Transboundary and emerging diseases, 65, 1, 114, 122, Feb. 2018, [Peer-reviewed]
  • First molecular detection and genetic characterization of Coxiella burnetii in Zambian dogs and rodents.
    Simbarashe Chitanga; Edgar Simulundu; Martin C Simuunza; Katendi Changula; Yongjin Qiu; Masahiro Kajihara; Ryo Nakao; Michelo Syakalima; Ayato Takada; Aaron S Mweene; Samson Mukaratirwa; Bernard M Hang'ombe
    Parasites & vectors, 11, 1, 40, 40, 17 Jan. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Coxiella burnetii, the causative agent of Q fever, is a zoonotic pathogen associated with sylvatic or domestic transmission cycles, with rodents being suspected to link the two transmission cycles. Infection and subsequent disease in humans has historically been associated with contact with infected livestock, especially sheep. However, recently there have been reports of Q fever outbreaks associated with contact with infected rodents and dogs. Studies exploring the potential role of these animal hosts in the epidemiology of Q fever in many developing countries in Africa are very limited. This study aimed to determine the potential role of rodents and dogs in the epidemiological cycle of C. burnetti in Zambia. Using pathogen-specific polymerase chain reaction assays targeting the 16S rRNA gene, C. burnetii was detected for the first time in 45% of rodents (9/20), in one shrew and in 10% of domestic dogs (15/150) screened in Zambia. Phylogenetic characterization of six samples based on the isocitrate synthase gene revealed that the strains were similar to a group of isolates from chronic human Q fever patients, goats and rodents reported in multiple continents. Considering the close proximity of domestic dogs and rodents to humans, especially in resource-limited communities, the presence of C. burnetii in these animals could be of significant public health importance. It is thus important to determine the burden of Q fever in humans in such resource-limited communities where there is close contact between humans, rodents and dogs.
  • Ebola virus requires a host scramblase for externalization of phosphatidylserine on the surface of viral particles.
    Asuka Nanbo; Junki Maruyama; Masaki Imai; Michiko Ujie; Yoichiro Fujioka; Shinya Nishide; Ayato Takada; Yusuke Ohba; Yoshihiro Kawaoka
    PLoS pathogens, 14, 1, e1006848, Jan. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Cell surface receptors for phosphatidylserine contribute to the entry of Ebola virus (EBOV) particles, indicating that the presence of phosphatidylserine in the envelope of EBOV is important for the internalization of EBOV particles. Phosphatidylserine is typically distributed in the inner layer of the plasma membrane in normal cells. Progeny virions bud from the plasma membrane of infected cells, suggesting that phosphatidylserine is likely flipped to the outer leaflet of the plasma membrane in infected cells for EBOV virions to acquire it. Currently, the intracellular dynamics of phosphatidylserine during EBOV infection are poorly understood. Here, we explored the role of XK-related protein (Xkr) 8, which is a scramblase responsible for exposure of phosphatidylserine in the plasma membrane of apoptotic cells, to understand its significance in phosphatidylserine-dependent entry of EBOV. We found that Xkr8 and transiently expressed EBOV glycoprotein GP often co-localized in intracellular vesicles and the plasma membrane. We also found that co-expression of GP and viral major matrix protein VP40 promoted incorporation of Xkr8 into ebolavirus-like particles (VLPs) and exposure of phosphatidylserine on their surface, although only a limited amount of phosphatidylserine was exposed on the surface of the cells expressing GP and/or VP40. Downregulating Xkr8 or blocking caspase-mediated Xkr8 activation did not affect VLP production, but they reduced the amount of phosphatidylserine on the VLPs and their uptake in recipient cells. Taken together, our findings indicate that Xkr8 is trafficked to budding sites via GP-containing vesicles, is incorporated into VLPs, and then promote the entry of the released EBOV to cells in a phosphatidylserine-dependent manner.
  • Molecular detection and characterization of zoonotic Anaplasma species in domestic dogs in Lusaka, Zambia
    Pipina A. Vlahakis; Simbarashe Chitanga; Martin C. Simuunza; Edgar Simulundu; Yongjin Qiu; Katendi Changula; Herman M. Chambaro; Masahiro Kajihara; Ryo Nakao; Ayato Takada; Aaron S. Mweene
    TICKS AND TICK-BORNE DISEASES, 9, 1, 39, 43, Jan. 2018, [Peer-reviewed]
    English, Scientific journal
  • Influenza A virus M2 protein: Roles from ingress to egress
    Rashid Manzoor; Manabu Igarashi; Ayato Takada
    International Journal of Molecular Sciences, 18, 12, E2649, MDPI AG, 07 Dec. 2017, [Peer-reviewed], [Last author, Corresponding author]
    English
  • Characterization of a Novel Bat Adenovirus Isolated from Straw-Colored Fruit Bat (Eidolon helvum).
    Hirohito Ogawa; Masahiro Kajihara; Naganori Nao; Asako Shigeno; Daisuke Fujikura; Bernard M Hang'ombe; Aaron S Mweene; Alisheke Mutemwa; David Squarre; Masao Yamada; Hideaki Higashi; Hirofumi Sawa; Ayato Takada
    Viruses, 9, 12, 04 Dec. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Bats are important reservoirs for emerging zoonotic viruses. For extensive surveys of potential pathogens in straw-colored fruit bats (Eidolon helvum) in Zambia, a total of 107 spleen samples of E. helvum in 2006 were inoculated onto Vero E6 cells. The cell culture inoculated with one of the samples (ZFB06-106) exhibited remarkable cytopathic changes. Based on the ultrastructural property in negative staining and cross-reactivity in immunofluorescence assays, the virus was suspected to be an adenovirus, and tentatively named E. helvum adenovirus 06-106 (EhAdV 06-106). Analysis of the full-length genome of 30,134 bp, determined by next-generation sequencing, showed the presence of 28 open reading frames. Phylogenetic analyses confirmed that EhAdV 06-106 represented a novel bat adenovirus species in the genus Mastadenovirus. The virus shared similar characteristics of low G + C contents with recently isolated members of species Bat mastadenoviruses E, F and G, from which EhAdV 06-106 diverged by more than 15% based on the distance matrix analysis of DNA polymerase amino acid sequences. According to the taxonomic criteria, we propose the tentative new species name "Bat mastadenovirus H". Because EhAdV 06-106 exhibited a wide in vitro cell tropism, the virus might have a potential risk as an emerging virus through cross-species transmission.
  • Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor
    Tatsunari Kondoh; Rashid Manzoor; Naganori Nao; Junki Maruyama; Wakako Furuyama; Hiroko Miyamoto; Asako Shigeno; Makoto Kuroda; Keita Matsuno; Daisuke Fujikura; Masahiro Kajihara; Reiko Yoshida; Manabu Igarashi; Ayato Takada
    PLOS ONE, 12, 10, e0186450, Oct. 2017, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • The Epidemiology of African Swine Fever in "Nonendemic" Regions of Zambia (1989-2015): Implications for Disease Prevention and Control
    Edgar Simulundu; Caesar H. Lubaba; Juanita van Heerden; Masahiro Kajihara; Liywalii Mataa; Herman Moses Chambaro; Yona Sinkala; Samuel Munalula Munjita; Hetron Mweemba Munang'andu; King Shimumbo Nalubamba; Kenny Samui; Girja Shanker Pandey; Ayato Takada; Aaron S. Mweene
    VIRUSES-BASEL, 9, 9, Sep. 2017, [Peer-reviewed]
    English
  • Rapid detection of all known ebolavirus species by reverse transcription-loop-mediated isothermal amplification (RT-LAMP)
    Olamide K. Oloniniyi; Yohei Kurosaki; Hiroko Miyamoto; Ayato Takada; Jiro Yasuda
    JOURNAL OF VIROLOGICAL METHODS, 246, 8, 14, Aug. 2017, [Peer-reviewed]
    English, Scientific journal
  • Genetic characterization of orf virus associated with an outbreak of severe orf in goats at a farm in Lusaka, Zambia (2015)
    Edgar Simulundu; Nandi Mtine; Thoko F. Kapalamula; Masahiro Kajihara; Yongjin Qiu; James Ngoma; Victor Zulu; Geoffrey Kwenda; Chrispin Chisanga; Isaac K. Phiri; Ayato Takada; Aaron S. Mweene
    ARCHIVES OF VIROLOGY, 162, 8, 2363, 2367, Aug. 2017, [Peer-reviewed]
    English, Scientific journal
  • Taxonomy of the order Mononegavirales: update 2017
    Gaya K. Amarasinghe; Yiming Bao; Christopher F. Basler; Sina Bavari; Martin Beer; Nicolas Bejerman; Kim R. Blasdell; Alisa Bochnowski; Thomas Briese; Alexander Bukreyev; Charles H. Calisher; Kartik Chandran; Peter L. Collins; Ralf G. Dietzgen; Olga Dolnik; Ralf Duerrwald; John M. Dye; Andrew J. Easton; Hideki Ebihara; Qi Fang; Pierre Formenty; Ron A. M. Fouchier; Elodie Ghedin; Robert M. Harding; Roger Hewson; Colleen M. Higgins; Jian Hong; Masayuki Horie; Anthony P. James; Daohong JiAng; Gary P. Kobinger; Hideki Kondo; Gael Kurath; Robert A. Lamb; Benhur Lee; Eric M. Leroy; Ming Li; Andrea Maisner; Elke Muhlberger; Sergey V. Netesov; Norbert Nowotny; Jean L. Patterson; Susan L. Payne; Janusz T. Paweska; Michael N. Pearson; Rick E. Randall; Peter A. Revill; Bertus K. Rima; Paul Rota; Dennis Rubbenstroth; Martin Schwemmle; Sophie J. Smither; Qisheng Song; David M. Stone; Ayato Takada; Calogero Terregino; Robert B. Tesh; Keizo Tomonaga; Noel Tordo; Jonathan S. Towner; Nikos Vasilakis; Viktor E. Volchkov; Victoria Wahl-Jensen; Peter J. Walker; Beibei Wang; David Wang; Fei Wang; Lin-Fa Wang; John H. Werren; Anna E. Whitfield; Zhichao Yan; Gongyin Ye; Jens H. Kuhn
    ARCHIVES OF VIROLOGY, 162, 8, 2493, 2504, Aug. 2017, [Peer-reviewed]
    English, Scientific journal
  • Rapid and broad detection of H5 hemagglutinin by an immunochromatographic kit using novel monoclonal antibody against highly pathogenic avian influenza virus belonging to the genetic clade 2.3.4.4
    Lam Thanh Nguyen; Kazunari Nakaishi; Keiko Motojima; Ayako Ohkawara; Erina Minato; Junki Maruyama; Takahiro Hiono; Keita Matsuno; Masatoshi Okamatsu; Takashi Kimura; Ayato Takada; Hiroshi Kida; Yoshihiro Sakoda
    PLOS ONE, 12, 8, e0182228, Aug. 2017, [Peer-reviewed]
    English, Scientific journal
  • Possibility and Challenges of Conversion of Current Virus Species Names to Linnaean Binomials
    Thomas S. Postler; Anna N. Clawson; Gaya K. Amarasinghe; Christopher F. Basler; Sbina Bavari; Maria Benko; Kim R. Blasdell; Thomas Briese; Michael J. Buchmeier; Alexander Bukreyev; Charles H. Calisher; Kartik Chandran; Remi Charrel; Christopher S. Clegg; Peter L. Collins; Juan Carlos de la Torre; Joseph L. Derisi; Ralf G. Dietzgen; Olga Dolnik; Ralf Duerrwald; John M. Dye; Andrew J. Easton; Sebastian Emonet; Pierre Formenty; Ron A. M. Fouchier; Elodie Ghedin; Jean-Paul Gonzalez; Balazs Harrach; Roger Hewson; Masayuki Horie; Daohong Jiang; Gary Kobinger; Hideki Kondo; Andrew M. Kropinski; Mart Krupovic; Gael Kurath; Robert A. Lamb; Eric M. Leroy; Igor S. Lukashevich; Andrea Maisner; Arcady R. Mushegian; Sergey V. Netesov; Norbert Nowotny; Jean L. Patterson; Susan L. Payne; Janusz T. Paweska; Clarence J. Peters; Sheli R. Radoshitzky; Bertus K. Rima; Victor Romanowski; Dennis Rubbenstroth; Sead Sabanadzovic; Helene Sanfacon; Maria S. Salvato; Martin Schwemmle; Sophie J. Smither; Mark D. Stenglein; David M. Stone; Ayato Takada; Robert B. Tesh; Keizo Tomonaga; Noel Tordo; Jonathan S. Towner; Nikos Vasilakis; Viktor E. Volchkov; Victoria Wahl-Jensen; Peter J. Walker; Lin-Fa Wang; Arvind Varsani; Anna E. Whitfield; F. Murilo Zerbini; Jens H. Kuhn
    SYSTEMATIC BIOLOGY, 66, 3, 463, 473, May 2017, [Peer-reviewed]
    English, Scientific journal
  • Implementation of Objective PASC-Derived Taxon Demarcation Criteria for Official Classification of Filoviruses
    Yiming Bao; Gaya K. Amarasinghe; Christopher F. Basler; Sina Bavari; Alexander Bukreyev; Kartik Chandran; Olga Dolnik; John M. Dye; Hideki Ebihara; Pierre Formenty; Roger Hewson; Gary P. Kobinger; Eric M. Leroy; Elke Muhlberger; Sergey V. Netesov; Jean L. Patterson; Janusz T. Paweska; Sophie J. Smither; Ayato Takada; Jonathan S. Towner; Viktor E. Volchkov; Victoria Wahl-Jensen; Jens H. Kuhn
    VIRUSES-BASEL, 9, 5, May 2017, [Peer-reviewed]
    English, Scientific journal
  • Clinical and subclinical bovine leukemia virus infection in a dairy cattle herd in Zambia
    Girja S. Pandey; Edgar Simulundu; Danstan Mwiinga; Kenny L. Samui; Aaron S. Mweene; Masahiro Kajihara; Alfred Mangani; Racheal Mwenda; Joseph Ndebe; Satoru Konnai; Ayato Takada
    ARCHIVES OF VIROLOGY, 162, 4, 1051, 1056, Apr. 2017, [Peer-reviewed]
    English, Scientific journal
  • エボラウイルスの糖タンパク質を標的化する大環状ペプチドの開発(Development of Macrocyclic Peptide Targeting Ebola Glycoprotein)
    Umemoto Shiori; Maruyama Junki; Takada Ayato; Suga Hiroaki
    日本薬学会年会要旨集, 137年会, 1, 67, 67, (公社)日本薬学会, Mar. 2017
    English
  • Putative RNA viral sequences detected in an Ixodes scapularis-derived cell line
    Ryo Nakao; Keita Matsuno; Yongjin Qiu; Junki Marilyama; Nao Eguchi; Naganori Nao; Masahiro Kajihara; Kentaro Yoshii; Hirofumi Sawa; Ayato Takada; Chihiro Sugimoto
    TICKS AND TICK-BORNE DISEASES, 8, 1, 103, 111, 2017, [Peer-reviewed]
    English, Scientific journal
  • Genetic Predisposition To Acquire a Polybasic Cleavage Site for Highly Pathogenic Avian Influenza Virus Hemagglutinin
    Naganori Nao; Junya Yamagishi; Hiroko Miyamoto; Manabu Igarashi; Rashid Manzoor; Aiko Ohnuma; Yoshimi Tsuda; Wakako Furuyama; Asako Shigeno; Masahiro Kajihara; Noriko Kishida; Reiko Yoshida; Ayato Takada
    MBIO, 8, 1, Jan. 2017, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Quantification of filovirus glycoprotein-specific antibodies
    Wakako Furuyama; Hiroko Miyamoto; Reiko Yoshida; Ayato Takada
    Methods in Molecular Biology, 1628, 309, 320, Humana Press Inc., 2017, [Peer-reviewed]
    English, In book
  • The Tetherin Antagonism of the Ebola Virus Glycoprotein Requires an Intact Receptor-Binding Domain and Can Be Blocked by GP1-Specific Antibodies
    Constantin Brinkmann; Inga Nehlmeier; Kerstin Walendy-Gnirss; Julia Nehls; Mariana Gonzalez Hernandez; Markus Hoffmann; Xiangguo Qiu; Ayato Takada; Michael Schindler; Stefan Poehlmann
    JOURNAL OF VIROLOGY, 90, 24, 11075, 11086, Dec. 2016, [Peer-reviewed]
    English, Scientific journal
  • Fc gamma-receptor IIa-mediated Src Signaling Pathway Is Essential for the Antibody-Dependent Enhancement of Ebola Virus Infection
    Wakako Furuyama; Andrea Marzi; Aaron B. Carmody; Junki Maruyama; Makoto Kuroda; Hiroko Miyamoto; Asuka Nanbo; Rashid Manzoor; Reiko Yoshida; Manabu Igarashi; Heinz Feldmann; Ayato Takada
    PLOS PATHOGENS, 12, 12, e1006139, Dec. 2016, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Lujo viral hemorrhagic fever: considering diagnostic capacity and preparedness in the wake of recent Ebola and Zika virus outbreaks
    Edgar Simulundu; Aaron S. Mweene; Katendi Changula; Mwaka Monze; Elizabeth Chizema; Peter Mwaba; Ayato Takada; Guiseppe Ippolito; Francis Kasolo; Alimuddin Zumla; Matthew Bates
    REVIEWS IN MEDICAL VIROLOGY, 26, 6, 446, 454, Nov. 2016, [Peer-reviewed]
    English
  • Development of an Immunochromatography Assay (QuickNavi-Ebola) to Detect Multiple Species of Ebolaviruses.
    Yoshida R; Muramatsu S; Akita H; Saito Y; Kuwahara M; Kato D; Changula K; Miyamoto H; Kajihara M; Manzoor R; Furuyama W; Marzi A; Feldmann H; Mweene A; Masumu J; Kapeteshi J; Muyembe-Tamfum JJ; Takada A
    The Journal of infectious diseases, 214, suppl 3, S185, S191, Oct. 2016, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, The latest outbreak of Ebola virus disease (EVD) in West Africa has highlighted the urgent need for the development of rapid and reliable diagnostic assays. We used monoclonal antibodies specific to the ebolavirus nucleoprotein to develop an immunochromatography (IC) assay (QuickNavi-Ebola) for rapid diagnosis of EVD. The IC assay was first evaluated with tissue culture supernatants of infected Vero E6 cells and found to be capable of detecting 103-104 focus-forming units/mL of ebolaviruses. Using serum samples from experimentally infected nonhuman primates, we confirmed that the assay could detect the viral antigen shortly after disease onset. It was also noted that multiple species of ebolaviruses could be detected by the IC assay. Owing to the simplicity of the assay procedure and absence of requirements for special equipment and training, QuickNavi-Ebola is expected to be a useful tool for rapid diagnosis of EVD.
  • Isolation of a sp nov Ljungan virus from wild birds in Japan
    Hiromichi Mitake; Yuji Fujii; Makoto Nagai; Naoto Ito; Kota Okadera; Kazuma Okada; Kento Nakagawa; Mai Kishimoto; Tetsuya Mizutani; Katsunori Okazaki; Yoshihiro Sakoda; Ayato Takada; Makoto Sugiyama
    JOURNAL OF GENERAL VIROLOGY, 97, 8, 1818, 1822, Aug. 2016, [Peer-reviewed]
    English, Scientific journal
  • Taxonomy of the order Mononegavirales: update 2016
    Claudio L. Afonso; Gaya K. Amarasinghe; Krisztian Banyai; Yiming Bao; Christopher F. Basler; Sina Bavari; Nicolas Bejerman; Kim R. Blasdell; Francois-Xavier Briand; Thomas Briese; Alexander Bukreyev; Charles H. Calisher; Kartik Chandran; Jiasen Cheng; Anna N. Clawson; Peter L. Collins; Ralf G. Dietzgen; Olga Dolnik; Leslie L. Domier; Ralf Duerrwald; John M. Dye; Andrew J. Easton; Hideki Ebihara; Szilvia L. Farkas; Juliana Freitas-Astua; Pierre Formenty; Ron A. M. Fouchier; Yanping Fu; Elodie Ghedin; Michael M. Goodin; Roger Hewson; Masayuki Horie; Timothy H. Hyndman; Daohong Jiang; Elliot W. Kitajima; Gary P. Kobinger; Hideki Kondo; Gael Kurath; Robert A. Lamb; Sergio Lenardon; Eric M. Leroy; Ci-Xiu Li; Xian-Dan Lin; Lijiang Liu; Ben Longdon; Szilvia Marton; Andrea Maisner; Elke Muhlberger; Sergey V. Netesov; Norbert Nowotny; Jean L. Patterson; Susan L. Payne; Janusz T. Paweska; Rick E. Randall; Bertus K. Rima; Paul Rota; Dennis Rubbenstroth; Martin Schwemmle; Mang Shi; Sophie J. Smither; Mark D. Stenglein; David M. Stone; Ayato Takada; Calogero Terregino; Robert B. Tesh; Jun-Hua Tian; Keizo Tomonaga; Noel Tordo; Jonathan S. Towner; Nikos Vasilakis; Martin Verbeek; Viktor E. Volchkov; Victoria Wahl-Jensen; John A. Walsh; Peter J. Walker; David Wang; Lin-Fa Wang; Thierry Wetzel; Anna E. Whitfield; Jiatao Xie; Kwok-Yung Yuen; Yong-Zhen Zhang; Jens H. Kuhn
    ARCHIVES OF VIROLOGY, 161, 8, 2351, 2360, Aug. 2016, [Peer-reviewed]
    English, Scientific journal
  • Constitutive aryl hydrocarbon receptor signaling constrains type I interferon-mediated antiviral innate defense
    Taisho Yamada; Hiromasa Horimoto; Takeshi Kameyama; Sumio Hayakawa; Hiroaki Yamato; Masayoshi Dazai; Ayato Takada; Hiroshi Kida; Debbie Bott; Angela C. Zhou; David Hutin; Tania H. Watts; Masahiro Asaka; Jason Matthews; Akinori Takaoka
    NATURE IMMUNOLOGY, 17, 6, 687, +, Jun. 2016, [Peer-reviewed]
    English, Scientific journal
  • Diagnosis and genotyping of African swine fever viruses from 2015 outbreaks in Zambia
    Jonas Thoromo; Edgar Simulundu; Herman M. Chambaro; Liywalii Mataa; Caesar H. Lubaba; Girja S. Pandey; Ayato Takada; Gerald Misinzo; Aaron S. Mweene
    ONDERSTEPOORT JOURNAL OF VETERINARY RESEARCH, 83, 1, a1095, Apr. 2016, [Peer-reviewed]
    English, Scientific journal
  • Molecular characterization of infectious bursal disease viruses detected in vaccinated commercial broiler flocks in Lusaka, Zambia
    Kunda Ndashe; Edgar Simulundu; Bernard M. Hang'ombe; Ladslav Moonga; Hirohito Ogawa; Ayato Takada; Aaron S. Mweene
    ARCHIVES OF VIROLOGY, 161, 3, 513, 519, Mar. 2016, [Peer-reviewed]
    English, Scientific journal
  • Development and Evaluation of Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) Assay Coupled with a Portable Device for Rapid Diagnosis of Ebola Virus Disease in Guinea
    Yohei Kurosaki; N’Faly Magassouba; Olamide K. Oloniniyi; Mahamoud S. Cherif; Saori Sakabe; Ayato Takada; Kenji Hirayama; Jiro Yasuda
    PLoS Neglected Tropical Diseases, 10, 2, e0004472, Public Library of Science, 22 Feb. 2016, [Peer-reviewed]
    English, Scientific journal
  • Development and Evaluation of Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) Assay Coupled with a Portable Device for Rapid Diagnosis of Ebola Virus Disease in Guinea
    Yohei Kurosaki; N'Faly Magassouba; Olamide K. Oloniniyi; Mahamoud S. Cherif; Saori Sakabe; Ayato Takada; Kenji Hirayama; Jiro Yasuda
    PLOS NEGLECTED TROPICAL DISEASES, 10, 2, Feb. 2016, [Peer-reviewed]
    English, Scientific journal
  • Discovery of an antibody for pan-ebolavirus therapy
    Wakako Furuyama; Andrea Marzi; Asuka Nanbo; Elaine Haddock; Junki Maruyama; Hiroko Miyamoto; Manabu Igarashi; Reiko Yoshida; Osamu Noyori; Heinz Feldmann; Ayato Takada
    SCIENTIFIC REPORTS, 6, 20514, Feb. 2016, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Characterization of the glycoproteins of bat-derived influenza viruses
    Junki Maruyama; Naganori Nao; Hiroko Miyamoto; Ken Maeda; Hirohito Ogawa; Reiko Yoshida; Manabu Igarashi; Ayato Takada
    VIROLOGY, 488, 43, 50, Jan. 2016, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Interferon-Induced Transmembrane Protein-Mediated Inhibition of Host Cell Entry of Ebolaviruses
    Florian Wrensch; Christina B. Karsten; Kerstin Gnirss; Markus Hoffmann; Kai Lu; Ayato Takada; Michael Winkler; Graham Simmons; Stefan Poehlmann
    JOURNAL OF INFECTIOUS DISEASES, 212, S210, S218, Oct. 2015, [Peer-reviewed]
    English, Scientific journal
  • Seroepidemiological Prevalence of Multiple Species of Filoviruses in Fruit Bats (Eidolon helvum) Migrating in Africa
    Hirohito Ogawa; Hiroko Miyamoto; Eri Nakayama; Reiko Yoshida; Ichiro Nakamura; Hirofumi Sawa; Akihiro Ishii; Yuka Thomas; Emiko Nakagawa; Keita Matsuno; Masahiro Kajihara; Junki Maruyama; Naganori Nao; Mieko Muramatsu; Makoto Kuroda; Edgar Simulundu; Katendi Changula; Bernard Hang'ombe; Boniface Namangala; Andrew Nambota; Jackson Katampi; Manabu Igarashi; Kimihito Ito; Heinz Feldmann; Chihiro Sugimoto; Ladslav Moonga; Aaron Mweene; Ayato Takada
    JOURNAL OF INFECTIOUS DISEASES, 212, S101, S108, Oct. 2015, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • A Single Amino Acid in the M1 Protein Responsible for the Different Pathogenic Potentials of H5N1 Highly Pathogenic Avian Influenza Virus Strains
    Naganori Nao; Masahiro Kajihara; Rashid Manzoor; Junki Maruyama; Reiko Yoshida; Mieko Muramatsu; Hiroko Miyamoto; Manabu Igarashi; Nao Eguchi; Masahiro Sato; Tatsunari Kondoh; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Ayato Takada
    PLOS ONE, 10, 9, e0137989, Sep. 2015, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Genetic and antigenic characterization of H5 and H7 influenza viruses isolated from migratory water birds in Hokkaido, Japan and Mongolia from 2010 to 2014
    Takahiro Hiono; Ayako Ohkawara; Kohei Ogasawara; Masatoshi Okamatsu; Tomokazu Tamura; Duc-Huy Chu; Mizuho Suzuki; Saya Kuribayashi; Shintaro Shichinohe; Ayato Takada; Hirohito Ogawa; Reiko Yoshida; Hiroko Miyamoto; Naganori Nao; Wakako Furuyama; Junki Maruyama; Nao Eguchi; Gerelmaa Ulziibat; Bazarragchaa Enkhbold; Munkhduuren Shatar; Tserenjav Jargalsaikhan; Selenge Byambadorj; Batchuluun Damdinjav; Yoshihiro Sakoda; Hiroshi Kida
    VIRUS GENES, 51, 1, 57, 68, Aug. 2015, [Peer-reviewed]
    English, Scientific journal
  • Molecular epidemiology of pathogenic Leptospira spp. in the straw-colored fruit bat (Eidolon helvum) migrating to Zambia from the Democratic Republic of Congo
    Hirohito Ogawa; Nobuo Koizumi; Aiko Ohnuma; Alisheke Mutemwa; Bernard M. Hang'ombe; Aaron S. Mweene; Ayato Takada; Chihiro Sugimoto; Yasuhiko Suzuki; Hiroshi Kida; Hirofumi Sawa
    INFECTION GENETICS AND EVOLUTION, 32, 143, 147, Jun. 2015, [Peer-reviewed]
    English, Scientific journal
  • Interaction between TIM-1 and NPC1 Is Important for Cellular Entry of Ebola Virus
    Makoto Kuroda; Daisuke Fujikura; Asuka Nanbo; Andrea Marzi; Osamu Noyori; Masahiro Kajihara; Junki Maruyama; Keita Matsuno; Hiroko Miyamoto; Reiko Yoshida; Heinz Feldmann; Ayato Takada
    JOURNAL OF VIROLOGY, 89, 12, 6481, 6493, Jun. 2015, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Pathological and molecular diagnosis of the 2013 African swine fever outbreak in Lusaka, Zambia.
    Yabe J; Hamambulu P; Simulundu E; Ogawa H; Kajihara M; Mori-Kajihara A; Changula-Chitanga K; Mwase M; Mweemba-Muwowo M; Chambaro HM; Mataa L; Hang'ombe B; Namangala B; Fandamu P; Sawa H; Takada A; Higashi H; Mweene AS
    Tropical animal health and production, 47, 2, 459, 463, Feb. 2015, [Peer-reviewed], [International Magazine]
    English, Scientific journal, African swine fever (ASF) is a highly contagious and fatal hemorrhagic viral disease of domestic pigs. The disease is widespread in sub-Saharan Africa and has repeatedly been introduced into other continents. The current study describes the diagnostic investigations of a hemorrhagic disease that was reported in pigs in Lusaka (October 2013), Zambia. Necropsy, histopathology, and molecular diagnosis using polymerase chain reaction and sequence analysis confirmed the disease to be ASF. The sequences obtained showed high similarity to previously isolated ASF viruses. Consistent surveillance and rapid diagnosis of the disease is recommended to prevent future outbreaks and economic losses as there is currently no vaccine against the disease.
  • Comprehensive Molecular Detection of Tick-Borne Phleboviruses Leads to the Retrospective Identification of Taxonomically Unassigned Bunyaviruses and the Discovery of a Novel Member of the Genus Phlebovirus
    Keita Matsuno; Carla Weisend; Masahiro Kajihara; Colette Matysiak; Brandi N. Williamson; Martin Simuunza; Aaron S. Mweene; Ayato Takada; Robert B. Tesh; Hideki Ebihara
    JOURNAL OF VIROLOGY, 89, 1, 594, 604, Jan. 2015, [Peer-reviewed]
    English, Scientific journal
  • A polymorphism of the TIM-1 IgV domain: Implications for the susceptibility to filovirus infection
    Makoto Kuroda; Daisuke Fujikura; Osamu Noyori; Masahiro Kajihara; Junki Maruyama; Hiroko Miyamoto; Reiko Yoshida; Ayato Takada
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 455, 3-4, 223, 228, Dec. 2014, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • The zoonotic potential of avian influenza viruses isolated from wild waterfowl in Zambia
    Edgar Simulundu; Naganori Nao; John Yabe; Nilton A. Muto; Thami Sithebe; Hirofumi Sawa; Rashid Manzoor; Masahiro Kajihara; Mieko Muramatsu; Akihiro Ishii; Hirohito Ogawa; Aaron S. Mweene; Ayato Takada
    ARCHIVES OF VIROLOGY, 159, 10, 2633, 2640, Oct. 2014, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names
    Jens H. Kuhn; Kristian G. Andersen; Yiming Bao; Sina Bavari; Stephan Becker; Richard S. Bennett; Nicholas H. Bergman; Olga Blinkova; Steven Bradfute; J. Rodney Brister; Alexander Bukreyev; Kartik Chandran; Alexander A. Chepurnov; Robert A. Davey; Ralf G. Dietzgen; Norman A. Doggett; Olga Dolnik; John M. Dye; Sven Enterlein; Paul W. Fenimore; Pierre Formenty; Alexander N. Freiberg; Robert F. Garry; Nicole L. Garza; Stephen K. Gire; Jean-Paul Gonzalez; Anthony Griffiths; Christian T. Happi; Lisa E. Hensley; Andrew S. Herbert; Michael C. Hevey; Thomas Hoenen; Anna N. Honko; Georgy M. Ignatyev; Peter B. Jahrling; Joshua C. Johnson; Karl M. Johnson; Jason Kindrachuk; Hans-Dieter Klenk; Gary Kobinger; Tadeusz J. Kochel; Matthew G. Lackemeyer; Daniel F. Lackner; Eric M. Leroy; Mark S. Lever; Elke Muehlberger; Sergey V. Netesov; Gene G. Olinger; Sunday A. Omilabu; Gustavo Palacios; Rekha G. Panchal; Daniel J. Park; Jean L. Patterson; Janusz T. Paweska; Clarence J. Peters; James Pettitt; Louise Pitt; Sheli R. Radoshitzky; Elena I. Ryabchikova; Erica Ollmann Saphire; Pardis C. Sabeti; Rachel Sealfon; Aleksandr M. Shestopalov; Sophie J. Smither; Nancy J. Sullivan; Robert Swanepoel; Ayato Takada; Jonathan S. Towner; Guido van der Groen; Viktor E. Volchkov; Valentina A. Volchkova; Victoria Wahl-Jensen; Travis K. Warren; Kelly L. Warfield; Manfred Weidmann; Stuart T. Nichol
    VIRUSES-BASEL, 6, 9, 3663, 3682, Sep. 2014, [Peer-reviewed]
    English, Scientific journal
  • Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection
    Yasushi Itoh; Reiko Yoshida; Shintaro Shichinohe; Megumi Higuchi; Hirohito Ishigaki; Misako Nakayama; Van Loi Pham; Hideaki Ishida; Mitsutaka Kitano; Masahiko Arikata; Naoko Kitagawa; Yachiyo Mitsuishi; Kazumasa Ogasawara; Hideaki Tsuchiya; Takahiro Hiono; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Mutsumi Ito; Le Quynh Mai; Yoshihiro Kawaoka; Hiroko Miyamoto; Mari Ishijima; Manabu Igarashi; Yasuhiko Suzuki; Ayato Takada
    PLOS PATHOGENS, 10, 6, e1004192, Jun. 2014, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Virus nomenclature below the species level: a standardized nomenclature for filovirus strains and variants rescued from cDNA
    Jens H. Kuhn; Yiming Bao; Sina Bavari; Stephan Becker; Steven Bradfute; Kristina Brauburger; J. Rodney Brister; Alexander A. Bukreyev; Yingyun Cai; Kartik Chandran; Robert A. Davey; Olga Dolnik; John M. Dye; Sven Enterlein; Jean-Paul Gonzalez; Pierre Formenty; Alexander N. Freiberg; Lisa E. Hensley; Thomas Hoenen; Anna N. Honko; Georgy M. Ignatyev; Peter B. Jahrling; Karl M. Johnson; Hans-Dieter Klenk; Gary Kobinger; Matthew G. Lackemeyer; Eric M. Leroy; Mark S. Lever; Elke Muehlberger; Sergey V. Netesov; Gene G. Olinger; Gustavo Palacios; Jean L. Patterson; Janusz T. Paweska; Louise Pitt; Sheli R. Radoshitzky; Elena I. Ryabchikova; Erica Ollmann Saphire; Aleksandr M. Shestopalov; Sophie J. Smither; Nancy J. Sullivan; Robert Swanepoel; Ayato Takada; Jonathan S. Towner; Guido van der Groen; Viktor E. Volchkov; Valentina A. Volchkova; Victoria Wahl-Jensen; Travis K. Warren; Kelly L. Warfield; Manfred Weidmann; Stuart T. Nichol
    ARCHIVES OF VIROLOGY, 159, 5, 1229, 1237, May 2014, [Peer-reviewed]
    English, Scientific journal
  • Role of the C-Terminal Region of Vervet Monkey Polyomavirus 1 VP1 in Virion Formation
    Hiroki Yamaguchi; Shintaro Kobayashi; Junki Maruyama; Michihito Sasaki; Ayato Takada; Takashi Kimura; Hirofumi Sawa; Yasuko Orba
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 76, 5, 637, 644, May 2014, [Peer-reviewed]
    English, Scientific journal
  • Discussions and decisions of the 2012-2014 International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group, January 2012-June 2013
    Alexander A. Bukreyev; Kartik Chandran; Olga Dolnik; John M. Dye; Hideki Ebihara; Eric M. Leroy; Elke Muehlberger; Sergey V. Netesov; Jean L. Patterson; Janusz T. Paweska; Erica Ollmann Saphire; Sophie J. Smither; Ayato Takada; Jonathan S. Towner; Viktor E. Volchkov; Travis K. Warren; Jens H. Kuhn
    ARCHIVES OF VIROLOGY, 159, 4, 821, 830, Apr. 2014, [Peer-reviewed]
    English, Scientific journal
  • Molecular Epidemiology of Paramyxoviruses in Frugivorous Eidolon helvum Bats in Zambia
    Walter Muleya; Michihito Sasaki; Yasuko Orba; Akihiro Ishii; Yuka Thomas; Emiko Nakagawa; Hirohito Ogawa; Bernard Hang'ombe; Boniface Namangala; Aaron Mweene; Ayato Takada; Takashi Kimura; Hirofumi Sawa
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 76, 4, 611, 614, Apr. 2014, [Peer-reviewed]
    English, Scientific journal
  • Heat Shock Protein 70 Modulates Influenza A Virus Polymerase Activity
    Rashid Manzoor; Kazumichi Kuroda; Reiko Yoshida; Yoshimi Tsuda; Daisuke Fujikura; Hiroko Miyamoto; Masahiro Kajihara; Hiroshi Kida; Ayato Takada
    JOURNAL OF BIOLOGICAL CHEMISTRY, 289, 11, 7599, 7614, Mar. 2014, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Characterization of the Envelope Glycoprotein of a Novel Filovirus, Lloviu Virus
    Junki Maruyama; Hiroko Miyamoto; Masahiro Kajihara; Hirohito Ogawa; Ken Maeda; Yoshihiro Sakoda; Reiko Yoshida; Ayato Takada
    JOURNAL OF VIROLOGY, 88, 1, 99, 109, Jan. 2014, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Comparison of Antiviral Activity between IgA and IgG Specific to Influenza Virus Hemagglutinin: Increased Potential of IgA for Heterosubtypic Immunity
    Mieko Muramatsu; Reiko Yoshida; Ayaka Yokoyama; Hiroko Miyamoto; Masahiro Kajihara; Junki Maruyama; Naganori Nao; Rashid Manzoor; Ayato Takada
    PLOS ONE, 9, 1, e85582, Jan. 2014, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Effect of the PB2 and M Genes on the Replication of H6 Influenza Virus in Chickens.
    Ozaki H; Guan Y; Peiris M; Webster R; Takada A; Webby R
    Influenza research and treatment, 2014, 547839, 2014, [Peer-reviewed]
  • Suppression of Fas-mediated apoptosis via steric shielding by filovirus glycoproteins
    Osamu Noyori; Eri Nakayama; Junki Maruyama; Reiko Yoshida; Ayato Takada
    Biochemical and Biophysical Research Communications, 441, 4, 994, 998, 29 Nov. 2013, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Differential potential for envelope glycoprotein-mediated steric shielding of host cell surface proteins among filoviruses
    Osamu Noyori; Keita Matsuno; Masahiro Kajihara; Eri Nakayama; Manabu Igarashi; Makoto Kuroda; Norikazu Isoda; Reiko Yoshida; Ayato Takada
    VIROLOGY, 446, 1-2, 152, 161, Nov. 2013, [Peer-reviewed]
    English, Scientific journal
  • The genetic and antigenic diversity of avian influenza viruses isolated from domestic ducks, muscovy ducks, and chickens in northern and southern Vietnam, 2010-2012
    Masatoshi Okamatsu; Tatsuya Nishi; Naoki Nomura; Naoki Yamamoto; Yoshihiro Sakoda; Kenji Sakurai; Huy Duc Chu; Long Pham Thanh; Long Van Nguyen; Nam Van Hoang; Tien Ngoc Tien; Reiko Yoshida; Ayato Takada; Hiroshi Kida
    VIRUS GENES, 47, 2, 317, 329, Oct. 2013, [Peer-reviewed]
    English, Scientific journal
  • Mapping of conserved and species-specific antibody epitopes on the Ebola virus nucleoprotein
    Katendi Changula; Reiko Yoshida; Osamu Noyori; Andrea Marzi; Hiroko Miyamoto; Mari Ishijima; Ayaka Yokoyama; Masahiro Kajihara; Heinz Feldmann; Aaron S. Mweene; Ayato Takada
    Virus Research, 176, 1-2, 83, 90, Sep. 2013, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • A novel Ebola virus expressing luciferase allows for rapid and quantitative testing of antivirals
    Thomas Hoenen; Allison Groseth; Julie Callison; Ayato Takada; Heinz Feldmann
    ANTIVIRAL RESEARCH, 99, 3, 207, 213, Sep. 2013, [Peer-reviewed]
    English, Scientific journal
  • Heterosubtypic Antiviral Activity of Hemagglutinin-Specific Antibodies Induced by Intranasal Immunization with Inactivated Influenza Viruses in Mice
    Mieko Muramatsu; Reiko Yoshida; Hiroko Miyamoto; Daisuke Tomabechi; Masahiro Kajihara; Junki Maruyama; Takashi Kimura; Rashid Manzoor; Kimihito Ito; Ayato Takada
    PLOS ONE, 8, 8, e71534, Aug. 2013, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Virus nomenclature below the species level: a standardized nomenclature for laboratory animal-adapted strains and variants of viruses assigned to the family Filoviridae
    Jens H. Kuhn; Yiming Bao; Sina Bavari; Stephan Becker; Steven Bradfute; J. Rodney Brister; Alexander A. Bukreyev; Yingyun Cai; Kartik Chandran; Robert A. Davey; Olga Dolnik; John M. Dye; Sven Enterlein; Jean-Paul Gonzalez; Pierre Formenty; Alexander N. Freiberg; Lisa E. Hensley; Anna N. Honko; Georgy M. Ignatyev; Peter B. Jahrling; Karl M. Johnson; Hans-Dieter Klenk; Gary Kobinger; Matthew G. Lackemeyer; Eric M. Leroy; Mark S. Lever; Loreen L. Lofts; Elke Muehlberger; Sergey V. Netesov; Gene G. Olinger; Gustavo Palacios; Jean L. Patterson; Janusz T. Paweska; Louise Pitt; Sheli R. Radoshitzky; Elena I. Ryabchikova; Erica Ollmann Saphire; Aleksandr M. Shestopalov; Sophie J. Smither; Nancy J. Sullivan; Robert Swanepoel; Ayato Takada; Jonathan S. Towner; Guido van der Groen; Viktor E. Volchkov; Victoria Wahl-Jensen; Travis K. Warren; Kelly L. Warfield; Manfred Weidmann; Stuart T. Nichol
    ARCHIVES OF VIROLOGY, 158, 6, 1425, 1432, Jun. 2013, [Peer-reviewed]
    English, Scientific journal
  • Cross-Reactivity of Secondary Antibodies against African Rodents and Application for Sero-Surveillance
    Ichiro Nakamura; Bernard Mudenda Hang'ombe; Hirofumi Sawa; Shintaro Kobayashi; Yasuko Orba; Akihiro Ishii; Yuka Thomas; Rie Isozumi; Kumiko Yoshimatsu; Aaron S. Mweene; Ayato Takada; Chihiro Sugimoto; Jiro Arikawa
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 75, 6, 819, 825, Jun. 2013, [Peer-reviewed]
    English, Scientific journal
  • Novel mutations in Marburg virus glycoprotein associated with viral evasion from antibody mediated immune pressure
    Masahiro Kajihara; Eri Nakayama; Andrea Marzi; Manabu Igarashi; Heinz Feldmann; Ayato Takada
    JOURNAL OF GENERAL VIROLOGY, 94, Pt 4, 876, 883, Apr. 2013, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Resampling Nucleotide Sequences with Closest-Neighbor Trimming and Its Comparison to Other Methods
    Kouki Yonezawa; Manabu Igarashi; Keisuke Ueno; Ayato Takada; Kimihito Ito
    PLoS ONE, 8, 2, e57684, 2, 27 Feb. 2013, [Peer-reviewed]
    English, Scientific journal
  • The PB2, PA, HA, NP, and NS genes of a highly pathogenic avian influenza virus A/whooper swan/Mongolia/3/2005 (H5N1) are responsible for pathogenicity in ducks
    Masahiro Kajihara; Yoshihiro Sakoda; Kosuke Soda; Kenji Minari; Masatoshi Okamatsu; Ayato Takada; Hiroshi Kida
    VIROLOGY JOURNAL, 10, 45, Feb. 2013, [Peer-reviewed]
    English, Scientific journal
  • Molecular Mechanisms Underlying Oseltamivir Resistance Mediated by an I117V Substitution in the Neuraminidase of Subtype H5N1 Avian Influenza A Viruses
    Ryo Takano; Maki Kiso; Manabu Igarashi; Quynh Mai Le; Masakazu Sekijima; Kimihito Ito; Ayato Takada; Yoshihiro Kawaoka
    JOURNAL OF INFECTIOUS DISEASES, 207, 1, 89, 97, Jan. 2013, [Peer-reviewed]
    English, Scientific journal
  • Inhibition of Marburg Virus Budding by Nonneutralizing Antibodies to the Envelope Glycoprotein
    Masahiro Kajihara; Andrea Marzi; Eri Nakayama; Takeshi Noda; Makoto Kuroda; Rashid Manzoor; Keita Matsuno; Heinz Feldmann; Reiko Yoshida; Yoshihiro Kawaoka; Ayato Takada
    JOURNAL OF VIROLOGY, 86, 24, 13467, 13474, Dec. 2012, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • エボラウイルス表層糖タンパク質に対する糖鎖修飾制御メカニズムの解明
    藤平 陽彦; 宇佐美 克明; 伝田 香里; 松野 啓太; 篠原 康郎; 佐藤 あやの; 高田 礼人; 入村 達郎
    日本生化学会大会プログラム・講演要旨集, 85回, 3T15, 08, (公社)日本生化学会, Dec. 2012
    Japanese
  • Molecular surveillance and phylogenetic analysis of Old World arenaviruses in Zambia
    Akihiro Ishii; Yuka Thomas; Ladslav Moonga; Ichiro Nakamura; Aiko Ohnuma; Bernard M. Hang'ombe; Ayato Takada; Aaron S. Mweene; Hirofumi Sawa
    JOURNAL OF GENERAL VIROLOGY, 93, 10, 2247, 2251, Oct. 2012, [Peer-reviewed]
    English, Scientific journal
  • Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity
    Peter S. Lee; Reiko Yoshida; Damian C. Ekiert; Naoki Sakai; Yasuhiko Suzuki; Ayato Takada; Ian A. Wilson
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109, 42, 17040, 17045, Oct. 2012, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Immune Parameters Correlate with Protection Against Ebola Virus Infection in Rodents and Nonhuman Primates
    Gary Wong; Jason S. Richardson; Stephane Pillet; Ami Patel; Xiangguo Qiu; Judie Alimonti; Jeff Hogan; Yi Zhang; Ayato Takada; Heinz Feldmann; Gary P. Kobinger
    SCIENCE TRANSLATIONAL MEDICINE, 4, 158, 158ra146, Oct. 2012, [Peer-reviewed]
    English, Scientific journal
  • Inhibitory effects of an M2-specific monoclonal antibody on different strains of influenza A virus
    Nilton Akio Muto; Reiko Yoshida; Tadaki Suzuki; Shintaro Kobayashi; Hiroichi Ozaki; Daisuke Fujikura; Rashid Manzoor; Mieko Muramatsu; Ayato Takada; Takashi Kimura; Hirofumi Sawa
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 60, 2-3, 71, 83, Aug. 2012, [Peer-reviewed]
    English, Scientific journal
  • Serological Evidence of Ebola Virus Infection in Indonesian Orangutans
    Chairul A. Nidom; Eri Nakayama; Reviany V. Nidom; Mohamad Y. Alamudi; Syafril Daulay; Indi N. L. P. Dharmayanti; Yoes P. Dachlan; Mohamad Amin; Manabu Igarashi; Hiroko Miyamoto; Reiko Yoshida; Ayato Takada
    PLOS ONE, 7, 7, e40740, Jul. 2012, [Peer-reviewed], [Last author]
    English, Scientific journal
  • Memory Immune Responses against Pandemic (H1N1) 2009 Influenza Virus Induced by a Whole Particle Vaccine in Cynomolgus Monkeys Carrying Mafa-A1*052:02
    Masahiko Arikata; Yasushi Itoh; Masatoshi Okamatsu; Toshinaga Maeda; Takashi Shiina; Keiko Tanaka; Shingo Suzuki; Misako Nakayama; Yoshihiro Sakoda; Hirohito Ishigaki; Ayato Takada; Hideaki Ishida; Kosuke Soda; Van Loi Pham; Hideaki Tsuchiya; Shinichiro Nakamura; Ryuzo Torii; Takeshi Shimizu; Hidetoshi Inoko; Iwao Ohkubo; Hiroshi Kida; Kazumasa Ogasawara
    PLOS ONE, 7, 5, e37220, May 2012, [Peer-reviewed]
    English, Scientific journal
  • Protective Efficacy of Neutralizing Monoclonal Antibodies in a Nonhuman Primate Model of Ebola Hemorrhagic Fever
    Andrea Marzi; Reiko Yoshida; Hiroko Miyamoto; Mari Ishijima; Yasuhiko Suzuki; Megumi Higuchi; Yukie Matsuyama; Manabu Igarashi; Eri Nakayama; Makoto Kuroda; Masayuki Saijo; Friederike Feldmann; Douglas Brining; Heinz Feldmann; Ayato Takada
    PLOS ONE, 7, 4, e36192, Apr. 2012, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Reintroduction of H5N1 highly pathogenic avian influenza virus by migratory water birds, causing poultry outbreaks in the 2010-2011 winter season in Japan
    Yoshihiro Sakoda; Hiroshi Ito; Yuko Uchida; Masatoshi Okamatsu; Naoki Yamamoto; Kosuke Soda; Naoki Nomura; Saya Kuribayashi; Shintaro Shichinohe; Yuji Sunden; Takashi Umemura; Tatsufumi Usui; Hiroichi Ozaki; Tsuyoshi Yamaguchi; Toshiyuki Murase; Toshihiro Ito; Takehiko Saito; Ayato Takada; Hiroshi Kida
    JOURNAL OF GENERAL VIROLOGY, 93, 3, 541, 550, Mar. 2012, [Peer-reviewed]
    English, Scientific journal
  • Adaptation of a Duck Influenza A Virus in Quail
    Shinya Yamada; Kyoko Shinya; Ayato Takada; Toshihiro Ito; Takashi Suzuki; Yasuo Suzuki; Quynh Mai Le; Masahito Ebina; Noriyuki Kasai; Hiroshi Kida; Taisuke Horimoto; Pierre Rivailler; Li Mei Chen; Ruben O. Donis; Yoshihiro Kawaoka
    JOURNAL OF VIROLOGY, 86, 3, 1411, 1420, Feb. 2012, [Peer-reviewed]
    English, Scientific journal
  • Osteopontin is critical to determine symptom severity of influenza through the regulation of NK cell population
    Kayoko Sato; Atsushi Iwai; Yosuke Nakayama; Junko Morimoto; Ayato Takada; Mitsuo Maruyama; Hiroshi Kida; Toshimitsu Uede; Tadaaki Miyazaki
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 417, 1, 274, 279, Jan. 2012, [Peer-reviewed]
    English, Scientific journal
  • Filovirus tropism: cellular molecules for viral entry
    Ayato Takada
    FRONTIERS IN MICROBIOLOGY, 3, 34, 2012, [Peer-reviewed], [Invited]
    English
  • Single Immunization With a Monovalent Vesicular Stomatitis Virus-Based Vaccine Protects Nonhuman Primates Against Heterologous Challenge With Bundibugyo ebolavirus
    Darryl Falzarano; Friederike Feldmann; Allen Grolla; Anders Leung; Hideki Ebihara; James E. Strong; Andrea Marzi; Ayato Takada; Shane Jones; Jason Gren; Joan Geisbert; Steven M. Jones; Thomas W. Geisbert; Heinz Feldmann
    JOURNAL OF INFECTIOUS DISEASES, 204, S1082, S1089, Nov. 2011, [Peer-reviewed]
    English, Scientific journal
  • Antibody-Dependent Enhancement of Marburg Virus Infection
    Eri Nakayama; Daisuke Tomabechi; Keita Matsuno; Noriko Kishida; Reiko Yoshida; Heinz Feldmann; Ayato Takada
    JOURNAL OF INFECTIOUS DISEASES, 204, S978, S985, Nov. 2011, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Novel Arenavirus, Zambia
    Akihiro Ishii; Yuka Thomas; Ladslav Moonga; Ichiro Nakamura; Aiko Ohnuma; Bernard Hang'ombe; Ayato Takada; Aaron Mweene; Hirofumi Sawa
    EMERGING INFECTIOUS DISEASES, 17, 10, 1921, 1924, Oct. 2011, [Peer-reviewed]
    English, Scientific journal
  • Gnarled-Trunk Evolutionary Model of Influenza A Virus Hemagglutinin
    Kimihito Ito; Manabu Igarashi; Yutaka Miyazaki; Teiji Murakami; Syaka Iida; Hiroshi Kida; Ayato Takada
    PLOS ONE, 6, 10, e25953, Oct. 2011, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Cross-Protective Peptide Vaccine against Influenza A Viruses Developed in HLA-A*2402 Human Immunity Model
    Toru Ichihashi; Reiko Yoshida; Chihiro Sugimoto; Ayato Takada; Kiichi Kajino
    PLOS ONE, 6, 9, e24626, Sep. 2011, [Peer-reviewed]
    English, Scientific journal
  • An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration
    Masahiro Kajihara; Keita Matsuno; Edgar Simulundu; Mieko Muramatsu; Osamu Noyori; Rashid Manzoor; Eri Nakayama; Manabu Igarashi; Daisuke Tomabechi; Reiko Yoshida; Masatoshi Okamatsu; Yoshihiro Sakoda; Kimihito Ito; Hiroshi Kida; Ayato Takada
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 59, 2-3, 89, 100, Aug. 2011, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Characterization of influenza A viruses isolated from wild waterfowl in Zambia
    Edgar Simulundu; Akihiro Ishii; Manabu Igarashi; Aaron S. Mweene; Yuka Suzuki; Bernard M. Hang' ombe; Boniface Namangala; Ladslav Moonga; Rashid Manzoor; Kimihito Ito; Ichiro Nakamura; Hirofumi Sawa; Chihiro Sugimoto; Hiroshi Kida; Chuma Simukonda; Wilbroad Chansa; Jack Chulu; Ayato Takada
    JOURNAL OF GENERAL VIROLOGY, 92, 6, 1416, 1427, Jun. 2011, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Prediction of the antigenic changes of the pandemic (H1N1) 2009 influenza virus hemagglutinin
    Manabu Igarashi; Kimihito Ito; Reiko Yoshida; Daisuke Tomabechi; Hiroshi Kida; Ayato Takada
    INFLUENZA AND OTHER RESPIRATORY VIRUSES, 5, 402, 404, May 2011, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin
    Katsuaki Usami; Keita Matsuno; Manabu Igarashi; Kaori Denda-Nagai; Ayato Takada; Tatsuro Irimura
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 407, 1, 74, 78, Apr. 2011, [Peer-reviewed]
    English, Scientific journal
  • Requirement for Siva-1 for replication of influenza A virus through apoptosis induction
    Takuya Shiozaki; Atsushi Iwai; Yoshihiro Kawaoka; Ayato Takada; Hiroshi Kida; Tadaaki Miyazaki
    JOURNAL OF GENERAL VIROLOGY, 92, 2, 315, 325, Feb. 2011, [Peer-reviewed]
    English, Scientific journal
  • A vaccine prepared from a non-pathogenic H5N1 influenza virus strain from the influenza virus library conferred protective immunity to chickens against the challenge with antigenically drifted highly pathogenic avian influenza virus
    Rozanah Asmah Abdul Samad; Naoki Nomura; Yoshimi Tsuda; Rashid Manzoor; Masahiro Kajihara; Daisuke Tomabechi; Takashi Sasaki; Norihide Kokumai; Toshiaki Ohgitani; Masatoshi Okamatsu; Ayato Takada; Yoshihiro Sakoda; Hiroshi Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 59, 1, 23, 29, Feb. 2011, [Peer-reviewed]
    English, Scientific journal
  • Detection of all known filovirus species by reverse transcription-polymerase chain reaction using a primer set specific for the viral nucleoprotein gene
    Hirohito Ogawa; Hiroko Miyamoto; Hideki Ebihara; Kimihito Ito; Shigeru Morikawa; Heinz Feldmann; Ayato Takada
    JOURNAL OF VIROLOGICAL METHODS, 171, 1, 310, 313, Jan. 2011, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Genetic characterization and susceptibility on poultry and mammal of H7N6 subtype avian influenza virus isolated in Japan in 2009
    Yuko Uchida; Katsushi Kanehira; Masaji Mase; Nobuhiro Takemae; Chiaki Watanabe; Tatsufumi Usui; Yoshikazu Fujimoto; Toshihiro Ito; Manabu Igarashi; Kimihito Ito; Ayato Takada; Yoshihiro Sakoda; Masatoshi Okamatsu; Yu Yamamoto; Kikuyasu Nakamura; Hiroshi Kida; Yasuaki Hiromoto; Tomoyuki Tsuda; Takehiko Saito
    VETERINARY MICROBIOLOGY, 147, 1-2, 1, 10, Jan. 2011, [Peer-reviewed]
    English, Scientific journal
  • Antigenic, genetic, and pathogenic characterization of H5N1 highly pathogenic avian influenza viruses isolated from dead whooper swans (Cygnus cygnus) found in northern Japan in 2008
    Masatoshi Okamatsu; Tomohisa Tanaka; Naoki Yamamoto; Yoshihiro Sakoda; Takashi Sasaki; Yoshimi Tsuda; Norikazu Isoda; Norihide Kokumai; Ayato Takada; Takashi Umemura; Hiroshi Kida
    VIRUS GENES, 41, 3, 351, 357, Dec. 2010, [Peer-reviewed]
    English, Scientific journal
  • C-type lectins do not act as functional receptors for filovirus entry into cells
    Keita Matsuno; Eri Nakayama; Osamu Noyori; Andrea Marzi; Hideki Ebihara; Tatsuro Irimura; Heinz Feldmann; Ayato Takada
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 403, 1, 144, 148, Dec. 2010, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Enzyme-Linked Immunosorbent Assay for Detection of Filovirus Species-Specific Antibodies
    Eri Nakayama; Ayaka Yokoyama; Hiroko Miyamoto; Manabu Igarashi; Noriko Kishida; Keita Matsuno; Andrea Marzi; Heinz Feldmann; Kimihito Ito; Masayuki Saijo; Ayato Takada
    CLINICAL AND VACCINE IMMUNOLOGY, 17, 11, 1723, 1728, Nov. 2010, [Peer-reviewed]
    English, Scientific journal
  • Characterization of H5N1 highly pathogenic avian influenza virus strains isolated from migratory waterfowl in Mongolia on the way back from the southern Asia to their northern territory
    Yoshihiro Sakoda; Sengee Sugar; Damdinjav Batchluun; Tseren-Ochir Erdene-Ochir; Masatoshi Okamatsu; Norikazu Isoda; Kosuke Soda; Hiroki Takakuwa; Yoshimi Tsuda; Naoki Yamamoto; Noriko Kishida; Keita Matsuno; Eri Nakayama; Masahiro Kajihara; Ayaka Yokoyama; Ayato Takada; Ruuragchaa Sodnomdarjaa; Hiroshi Kida
    VIROLOGY, 406, 1, 88, 94, Oct. 2010, [Peer-reviewed]
    English, Scientific journal
  • Characterization of human single-chain antibodies against highly pathogenic avian influenza H5N1 viruses: mimotope and neutralizing activity
    JiuPian Yang; Reiko Yoshida; Yuki Kariya; Xu Zhang; Shuhei Hashiguchi; Toshihiro Nakashima; Yasuo Suda; Ayato Takada; Yuji Ito; Kazuhisa Sugimura
    JOURNAL OF BIOCHEMISTRY, 148, 4, 507, 515, Oct. 2010, [Peer-reviewed]
    English, Scientific journal
  • Influenza A Virus Polymerase Inhibits Type I Interferon Induction by Binding to Interferon beta Promoter Stimulator 1
    Atsushi Iwai; Takuya Shiozaki; Taro Kawai; Shizuo Akira; Yoshihiro Kawaoka; Ayato Takada; Hiroshi Kida; Tadaaki Miyazaki
    JOURNAL OF BIOLOGICAL CHEMISTRY, 285, 42, 32064, 32074, Oct. 2010, [Peer-reviewed]
    English, Scientific journal
  • Different Potential of C-Type Lectin-Mediated Entry between Marburg Virus Strains
    Keita Matsuno; Noriko Kishida; Katsuaki Usami; Manabu Igarashi; Reiko Yoshida; Eri Nakayama; Masayuki Shimojima; Heinz Feldmann; Tatsuro Irimura; Yoshihiro Kawaoka; Ayato Takada
    JOURNAL OF VIROLOGY, 84, 10, 5140, 5147, May 2010, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Predicting the Antigenic Structure of the Pandemic (H1N1) 2009 Influenza Virus Hemagglutinin
    Manabu Igarashi; Kimihito Ito; Reiko Yoshida; Daisuke Tomabechi; Hiroshi Kida; Ayato Takada
    PLOS ONE, 5, 1, e8553, Jan. 2010, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Characterization of H3N6 avian influenza virus isolated from a wild white pelican in Zambia
    Edgar Simulundu; Aaron S. Mweene; Daisuke Tomabechi; Bernard M. Hang'ombe; Akihiro Ishii; Yuka Suzuki; Ichiro Nakamura; Hirofumi Sawa; Chihiro Sugimoto; Kimihito Ito; Hiroshi Kida; Lewis Saiwana; Ayato Takada
    ARCHIVES OF VIROLOGY, 154, 9, 1517, 1522, Sep. 2009, [Peer-reviewed]
    English, Scientific journal
  • MGL/CD301を介するエボラウイルス感染増強に関わる表層糖蛋白質の構造的特徴(Structural features of Ebola viral envelope glycoproteins responsible for the enhancement of infection through the interaction with MGL/CD301)
    宇佐美 克明; 松野 啓太; 五十嵐 学; 伝田 香里; 高田 礼人; 入村 達郎
    日本生化学会大会プログラム・講演要旨集, 82回, 4T20p, 16, (公社)日本生化学会, Sep. 2009
    English
  • Cross-Protective Potential of a Novel Monoclonal Antibody Directed against Antigenic Site B of the Hemagglutinin of Influenza A Viruses
    Reiko Yoshida; Manabu Igarashi; Hiroichi Ozaki; Noriko Kishida; Daisuke Tomabechi; Hiroshi Kida; Kimihito Ito; Ayato Takada
    PLOS PATHOGENS, 5, 3, e1000350, Mar. 2009, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Cross-Glade protective immunity of H5N1 influenza vaccines in a mouse model
    Shin Murakami; Ayaka Iwasa; Kiyoko Iwatsuki-Horimoto; Mutsumi Ito; Maki Kiso; Hiroshi Kida; Ayato Takada; Chairul A. Nidom; Le Quynh Mai; Shinya Yamada; Hirotaka Imai; Yuko Sakai-Tagawa; Yoshihiro Kawaoka; Taisuke Horimoto
    VACCINE, 26, 50, 6398, 6404, Nov. 2008, [Peer-reviewed]
    English, Scientific journal
  • Antigenic and genetic analysis of H5 influenza viruses isolated from water birds for the purpose of vaccine use
    Kosuke Soda; Hiroichi Ozaki; Yoshihiro Sakoda; Norikazu Isoda; Yoshinari Haraguchi; Saori Sakabe; Noritaka Kuboki; Noriko Kishida; Ayato Takada; Hiroshi Kida
    ARCHIVES OF VIROLOGY, 153, 11, 2041, 2048, Nov. 2008, [Peer-reviewed]
    English, Scientific journal
  • H2N5 influenza virus isolates from terns in Australia: genetic reassortants between those of the Eurasian and American lineages
    Noriko Kishida; Yoshihiro Sakoda; Mai Shiromoto; Gui-Rong Bai; Norikazu Isoda; Ayato Takada; Graeme Laver; Hiroshi Kida
    VIRUS GENES, 37, 1, 16, 21, Aug. 2008, [Peer-reviewed]
    English, Scientific journal
  • Genetically destined potentials for N-linked glycosylation of influenza virus hemagglutinin
    Manabu Igarashi; Kimihito Ito; Hiroshi Kida; Ayato Takada
    VIROLOGY, 376, 2, 323, 329, Jul. 2008, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Epitopes required for antibody-dependent enhancement of Ebola virus infection
    Ayato Takada; Hideki Ebihara; Heinz Feldmann; Thomas W. Geisbert; Yoshihiro Kawaoka
    JOURNAL OF INFECTIOUS DISEASES, 196, S347, S356, Nov. 2007, [Peer-reviewed]
    English, Scientific journal
  • Rapid and simple detection of Ebola virus by reverse transcription-loop-mediated isothermal amplification
    Yohei Kurosaki; Ayato Takada; Hideki Ebihara; Allen Grolla; Naoki Kamo; Heinz Feldmann; Yoshihiro Kawacka; Jiro Yasuda
    JOURNAL OF VIROLOGICAL METHODS, 141, 1, 78, 83, Apr. 2007, [Peer-reviewed]
    English, Scientific journal
  • Changes in Cellular Composition and Induction of Cell Death in the Spleen Are Correlated to the Disease Symptoms in Response to Influenza A Virus
    Sato Kayoko; Fujikura Daisuke; Takada Ayato; Kida Hiroshi; Miyazaki Tadaaki
    JOURNAL OF IMMUNOLOGY, 178, 01 Apr. 2007, [Peer-reviewed]
  • Contributions of two nuclear localization signals of influenza A virus nucleoprotein to viral replication
    Makoto Ozawa; Ken Fujii; Yukiko Muramoto; Shinya Yamada; Seiya Yamayoshi; Ayato Takada; Hideo Goto; Taisuke Horimoto; Yoshihiro Kawaoka
    JOURNAL OF VIROLOGY, 81, 1, 30, 41, Jan. 2007, [Peer-reviewed]
    English, Scientific journal
  • Protective efficacy of neutralizing antibodies against Ebola virus infection
    Ayato Takada; Hideki Ebihara; Sueven Jones; Heinz Feldmann; Yoshihiro Kawaoka
    VACCINE, 25, 6, 993, 999, Jan. 2007, [Peer-reviewed]
    English, Scientific journal
  • Bovine and water buffalo Mx2 genes: Polymorphism and antiviral activity
    H. A.E. Babiker; Y. Nakatsu; K. Yamada; A. Yoneda; A. Takada; J. Ueda; H. Hata; T. Watanabe
    Immunogenetics, 59, 1, 59, 67, Jan. 2007, [Peer-reviewed]
    English, Scientific journal
  • Tyro3 family-mediated cell entry of Ebola and Marburg viruses
    Masayuki Shimojima; Ayato Takada; Hideki Ebihara; Gabriele Neumann; Kouki Fujioka; Tatsuro Irimura; Steven Jones; Heinz Feldmann; Yoshihiro Kawaoka
    JOURNAL OF VIROLOGY, 80, 20, 10109, 10116, Oct. 2006, [Peer-reviewed]
    English, Scientific journal
  • Assembly and budding of Ebolavirus
    Takeshi Noda; Hideki Ebihara; Yukiko Muramoto; Ken Fujii; Ayato Takada; Hiroshi Sagara; Jin Hyun Kim; Hiroshi Kida; Heinz Feldmann; Yoshihiro Kawaoka
    PLOS PATHOGENS, 2, 9, 864, 872, Sep. 2006, [Peer-reviewed]
    English, Scientific journal
  • Molecular determinants of Ebola virus virulence in mice
    Hideki Ebihara; Ayato Takada; Darwyn Kobasa; Steven Jones; Gabriele Neumann; Steven Theriault; Mike Bray; Heinz Feldmann; Yoshihiro Kawaoka
    PLOS PATHOGENS, 2, 7, 705, 711, Jul. 2006, [Peer-reviewed]
    English, Scientific journal
  • Data Mining in Amino Acid Sequences of H3N2 Influenza Viruses Isolated during 1968 to 2006.
    Ito K; Igarashi M; Takada A
    Knowledge Media Technologies, 21, 154, 158, TU Ilmenau, Jul. 2006, [Peer-reviewed]
    English, The hemagglutinin (HA) of influenza viruses undergoes antigenic drift to escape from antibody-mediated immune pressure. In order to predict possible structural changes of the HA molecules in future, it is important to understand the patterns of amino acid mutations and structural changes in the past. We performed a retrospective and comprehensive analysis of structural changes in H3 hemagglutinins of human influenza viruses isolated during 1968 to 2006. Amino acid sequence data of more than 2000 strains have been collected from NCBI Influenza virus resources. Information theoretic analysis of the collected sequences revealed a number of simultaneous mutations of amino acids at two or more different positions (correlated mutations). We also calculated the net charge of the HA1 subunit, based on thenumber of charged amino acid residues, and found that the net charge increased linearly from 1968 to 1984 and, after then, has been saturated. This level of the net charge may be an upper limit for H3 HA to be functional. It is noted that "correlated mutations" with the conversion of acidic and basic amino acid residues between two different positions were frequently found after 1984, suggesting that these mutations contributed to counterbalancing effect to keep the net charge of the HA . These approaches may open the way to find the direction of future antigenic drift of influenza viruses.
  • Disease constraints for utilization of the African buffalo (Syncerus caffer) on game ranches in Zambia
    Hetron M. Munang'andu; Victor M. Siamudaala; Andrew Nambota; John M. Bwalya; Musso Munyeme; Aaron S. Mweene; Ayato Takada; Hiroshi Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 54, 1, 3, 13, May 2006, [Peer-reviewed]
    English
  • Ecology and epidemiology of anthrax in cattle and humans in Zambia
    Victor M. Siamudaala; John M. Bwalya; Hetron M. Munang'andu; Peter G. Sinyangwe; Fred Banda; Aaron S. Mweene; Ayato Takada; Hiroshi Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 54, 1, 15, 23, May 2006, [Peer-reviewed]
    English
  • The development and characterization of H5 influenza virus vaccines derived from a 2003 human isolate
    T Horimoto; A Takada; K Fujii; H Goto; M Hatta; S Watanabe; K Iwatsuki-Horimoto; M Ito; Y Tagawa-Sakai; S Yamada; H Ito; T Ito; M Imai; S Itamura; T Odagiri; M Tashiro; W Lim; Y Guan; M Peiris; Y Kawaoka
    VACCINE, 24, 17, 3669, 3676, Apr. 2006, [Peer-reviewed]
    English, Scientific journal
  • Hierarchy among viral RNA (vRNA) segments in their role in vRNA incorporation into influenza A virions
    Y Muramoto; A Takada; K Fujii; T Noda; K Iwatsuki-Horimoto; S Watanabe; T Horimoto; H Kida; Y Kawaoka
    JOURNAL OF VIROLOGY, 80, 5, 2318, 2325, Mar. 2006, [Peer-reviewed]
    English, Scientific journal
  • Detection of cell-cell fusion mediated by Ebola virus glycoproteins
    S Bar; A Takada; Y Kawaoka; M Alizon
    JOURNAL OF VIROLOGY, 80, 6, 2815, 2822, Mar. 2006, [Peer-reviewed]
    English, Scientific journal
  • The amino-terminal residue of glycoprotein B is critical for neutralization of bovine herpesvirus 1
    K Okazaki; S Fujii; A Takada; H Kida
    VIRUS RESEARCH, 115, 2, 105, 111, Feb. 2006, [Peer-reviewed]
    English, Scientific journal
  • Highly pathogenic H5N1 influenza virus causes coagulopathy in chickens
    Y Muramoto; H Ozaki; A Takada; CH Park; Y Sunden; T Umemura; Y Kawaoka; H Matsuda; H Kida
    MICROBIOLOGY AND IMMUNOLOGY, 50, 1, 73, 81, 2006, [Peer-reviewed]
    English, Scientific journal
  • Architecture of ribonucleoprotein complexes in influenza A virus particles
    T Noda; H Sagara; A Yen; A Takada; H Kida; RH Cheng; Y Kawaoka
    NATURE, 439, 7075, 490, 492, Jan. 2006, [Peer-reviewed]
    English, Scientific journal
  • Avian flu - Isolation of drug-resistant H5N1 virus
    QM Le; M Kiso; K Someya; YT Sakai; TH Nguyen; KHL Nguyen; ND Pham; HH Ngyen; S Yamada; Y Muramoto; T Horimoto; A Takada; H Goto; T Suzuki; Y Suzuki; Y Kawaoka
    NATURE, 437, 7062, 1108, 1108, Oct. 2005, [Peer-reviewed]
    English
  • Characterization of a human H5N1 influenza A virus isolated in 2003
    K Shinya; M Hatta; S Yamada; A Takada; S Watanabe; P Halfmann; T Horimoto; G Neumann; JH Kim; W Lim; Y Guan; M Peiris; M Kiso; T Suzuki; Y Suzuki; Y Kawaoka
    JOURNAL OF VIROLOGY, 79, 15, 9926, 9932, Aug. 2005, [Peer-reviewed]
    English, Scientific journal
  • Ebola virus VP40 late domains are not essential for viral replication in cell culture
    G Neumann; H Ebihara; A Takada; T Noda; D Kobasa; LD Jasenosky; S Watanabe; JH Kim; H Feldmann; Y Kawaoka
    JOURNAL OF VIROLOGY, 79, 16, 10300, 10307, Aug. 2005, [Peer-reviewed]
    English, Scientific journal
  • Live bivalent vaccine for parainfluenza and influenza virus infections
    Y Maeda; M Hatta; A Takada; T Watanabe; H Goto; G Neumann; Y Kawaoka
    JOURNAL OF VIROLOGY, 79, 11, 6674, 6679, Jun. 2005, [Peer-reviewed]
    English, Scientific journal
  • Importance of both the coding and the segment-specific noncoding regions of the influenza a virus NS segment for its efficient incorporation into virions
    K Fujii; Y Fujii; T Noda; Y Muramoto; T Watanabe; A Takada; H Goto; T Horimoto; Y Kawaoka
    JOURNAL OF VIROLOGY, 79, 6, 3766, 3774, Mar. 2005, [Peer-reviewed]
    English, Scientific journal
  • Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus
    D Kobasa; A Takada; K Shinya; M Hatta; P Halfmann; S Theriault; H Suzuki; H Nishimura; K Mitamura; N Sugaya; T Usui; T Murata; Y Maeda; S Watanabe; M Suresh; T Suzuki; Y Suzuki; H Feldmann; Y Kawaoka
    NATURE, 431, 7009, 703, 707, Oct. 2004, [Peer-reviewed]
    English, Scientific journal
  • A protective immune response in mice to viral components other than hemagglutinin in a live influenza A virus vaccine model
    T Horimoto; A Takada; K Iwatsuki-Horimoto; Y Kawaoka
    VACCINE, 22, 17-18, 2244, 2247, Jun. 2004, [Peer-reviewed]
    English, Scientific journal
  • Genetic polymorphisms and antiviral activity in the bovine MX1 gene
    Y. Nakatsu; K. Yamada; J. Ueda; A. Onogi; G. P. Ables; M. Nishibori; H. Hata; A. Takada; K. Sawai; Y. Tanabe; M. Morita; M. Daikohara; T. Watanabe
    Animal Genetics, 35, 3, 182, 187, Jun. 2004, [Peer-reviewed]
    English, Scientific journal
  • Native antiviral specificity of chicken Mx protein depends on amino acid variation at position 631
    J. H. Ko; A. Takada; T. Mitsuhashi; T. Agui; T. Watanabe
    Animal Genetics, 35, 2, 119, 122, Apr. 2004, [Peer-reviewed]
    English, Scientific journal
  • A型インフルエンザウイルスPB2遺伝子分節のパッケージングと粒子形成に必要な領域
    村本 裕紀子; 高田 礼人; 藤井 健; 堀本 研子; 渡辺 真治; 喜田 宏; 河岡 義裕
    日本獣医学会学術集会講演要旨集, 137回, 91, 91, (公社)日本獣医学会, Mar. 2004
    Japanese
  • Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry
    A Takada; K Fujioka; M Tsuiji; A Morikawa; N Higashi; H Ebihara; D Kobasa; H Feldmann; T Irimura; Y Kawaoka
    JOURNAL OF VIROLOGY, 78, 6, 2943, 2947, Mar. 2004, [Peer-reviewed]
    English, Scientific journal
  • Biological significance of the U residue at the -3 position of the mRNA sequences of influenza A viral segments PB1 and NA
    Y Maeda; H Goto; T Horimoto; A Takada; Y Kawaoka
    VIRUS RESEARCH, 100, 2, 153, 157, Mar. 2004, [Peer-reviewed]
    English, Scientific journal
  • Production of novel Ebola virus-like particles from cDNAs: an alternative to Ebola virus generation by reverse genetics
    S Watanabe; T Watanabe; T Noda; A Takada; H Feldmann; LD Jasenosky; Y Kawaoka
    JOURNAL OF VIROLOGY, 78, 2, 999, 1005, Jan. 2004, [Peer-reviewed]
    English, Scientific journal
  • Induction of interferon-inducible protein-10 and monokine induced by interferon-gamma from human endothelial cells infected with Influenza A virus
    N Ishiguro; A Takada; M Yoshioka; Ma, X; H Kikuta; H Kida; K Kobayashi
    ARCHIVES OF VIROLOGY, 149, 1, 17, 34, Jan. 2004, [Peer-reviewed]
    English, Scientific journal
  • Intranasal immunization with formalin-inactivated virus vaccine induces a broad spectrum of heterosubtypic immunity against influenza virus infection in mice
    A Takada; S Matsushita; A Ninomiya; Y Kawaoka; H Kida
    OPTIONS FOR THE CONTROL OF INFLUENZA V, 1263, 618, 621, 2004, [Peer-reviewed]
    English, International conference proceedings
  • Potential for use of influenza A viruses with chimeric (type A/B) hemagglutinins as vaccines.
    Horimoto T; Takada A; Iwatsuki-Horimoto K; Hatta M; Goto H; Kawaoka Y
    Options for the Control of Influenza V, ICS1263, 622, 625, 2004, [Peer-reviewed]
  • Preparation of a panel of avian influenza viruses of different subtypes for vaccine strains against future pandemics.
    Sakoda Y; Okazaki K; Takada A; Ito Y; Tamai K; Okamatsu M; Ito T; Shortridge KF; Webster RG; Kida H
    Options for the Control of Influenza V, International congress series, 1263, 674, 677, 2004, [Peer-reviewed]
    English, Scientific journal
  • Persistence of viral RNA segments in the central nervous system of mice after recovery from acute influenza A virus infection
    Park CH; Matsuda K; Sunden Y; Ninomiya A; Takada A; Ito H; Kimura T; Ochiai K; Kida H; Umemura T
    Veterinary Microbiology, 97, 259, 268, Dec. 2003, [Peer-reviewed]
    English, Scientific journal
  • Neurotropism of the 1997 Hong Kong H5N1 influenza virus in mice
    H Tanaka; CH Park; A Ninomiya; H Ozaki; A Takada; T Umemura; H Kida
    VETERINARY MICROBIOLOGY, 95, 1-2, 1, 13, Aug. 2003, [Peer-reviewed]
    English, Scientific journal
  • Intranasal immunization with formalin-inactivated virus vaccine induces a broad spectrum of heterosubtypic immunity against influenza A virus infection in mice
    A Takada; S Matsushita; A Ninomiya; Y Kawaoka; H Kida
    VACCINE, 21, 23, 3212, 3218, Jul. 2003, [Peer-reviewed]
    English, Scientific journal
  • Antibody-dependent enhancement of Ebola virus infection
    A Takada; H Feldmann; TG Ksiazek; Y Kawaoka
    JOURNAL OF VIROLOGY, 77, 13, 7539, 7544, Jul. 2003, [Peer-reviewed]
    English, Scientific journal
  • Generation of influenza A viruses with chimeric (type A/B) hemagglutinins
    T Horimoto; A Takada; K Iwatsuki-Horimoto; M Hatta; H Goto; Y Kawaoka
    JOURNAL OF VIROLOGY, 77, 14, 8031, 8038, Jul. 2003, [Peer-reviewed]
    English, Scientific journal
  • 強毒インフルエンザウイルスは血液凝固不全を引き起こす
    村本 裕紀子; 尾崎 弘一; 高田 礼人; 朴 天鎬; 寸田 祐嗣; 梅村 孝司; 河岡 義裕; 喜田 宏
    日本獣医学会学術集会講演要旨集, 135回, 128, 128, (公社)日本獣医学会, Mar. 2003
    Japanese
  • Identification of protective epitopes on Ebola virus glycoprotein at the single amino acid level by using recombinant vesicular stomatitis viruses
    A Takada; H Feldmann; U Stroeher; M Bray; S Watanabe; H Ito; M McGregor; Y Kawaoka
    JOURNAL OF VIROLOGY, 77, 2, 1069, 1074, Jan. 2003, [Peer-reviewed]
    English, Scientific journal
  • Seroepidemiological evidence of avian H4, H5, and H9 influenza A virus transmission to pigs in southeastern China
    A Ninomiya; A Takada; K Okazaki; KF Shortridge; H Kida
    VETERINARY MICROBIOLOGY, 88, 2, 107, 114, Aug. 2002, [Peer-reviewed]
    English, Scientific journal
  • Intranasal administration of a synthetic peptide vaccine encapsulated in liposome together with an anti-CD40 antibody induces protective immunity against influenza A virus in mice
    A Ninomiya; K Ogasawara; K Kajino; A Takada; H Kida
    VACCINE, 20, 25-26, 3123, 3129, Aug. 2002, [Peer-reviewed]
    English, Scientific journal
  • Ebola virus VP40 drives the formation of virus-like filamentous particles along with GP
    T Noda; H Sagara; E Suzuki; A Takada; H Kida; Y Kawaoka
    JOURNAL OF VIROLOGY, 76, 10, 4855, 4865, May 2002, [Peer-reviewed]
    English, Scientific journal
  • Polymorphisms and the differential antiviral activity of the chicken Mx gene
    JH Ko; HK Jin; A Asano; A Takada; A Ninomiya; H Kida; H Hokiyama; M Ohara; M Tsuzuki; M Nishibori; M Mizutani; T Watanabe
    GENOME RESEARCH, 12, 4, 595, 601, Apr. 2002, [Peer-reviewed]
    English
  • The invasion routes of neurovirulent A Hong Kong 483/97 (H5N1) influenza virus into the central nervous system after respiratory infection in mice
    CH Park; M Ishinaka; A Takada; H Kida; T Kimura; K Ochiai; T Umemura
    ARCHIVES OF VIROLOGY, 147, 7, 1425, 1436, 2002, [Peer-reviewed]
    English, Scientific journal
  • The loss of enzyme activities by a single amino acid substitution of a newly cloned rabbit CYP2D isozyme, CYP2D24
    Mayumi Ishizuka; Yukio Yamamoto; Ayato Takada; Akio Kazusaka; Shoichi Fujita
    International Congress Series, 1233, C, 121, 126, 2002, [Peer-reviewed]
    English, Scientific journal
  • Plasminogen-binding activity of neuraminidase determines the pathogenicity of influenza A virus
    H Goto; K Wells; A Takada; Y Kawaoka
    JOURNAL OF VIROLOGY, 75, 19, 9297, 9301, Oct. 2001, [Peer-reviewed]
    English, Scientific journal
  • Primary target cells of virulent strains of type A influenza virus in chicken embryos
    CH Park; H Ozaki; A Takada; H Kida; K Ochiai; T Umemura
    AVIAN PATHOLOGY, 30, 3, 269, 272, Jun. 2001, [Peer-reviewed]
    English, Scientific journal
  • Infectivity-enhancing antibodies to ebola virus glycoprotein
    A Takada; S Watanabe; K Okazaki; H Kida; Y Kawaoka
    JOURNAL OF VIROLOGY, 75, 5, 2324, 2330, Mar. 2001
    English, Scientific journal
  • Ebola virus glycoprotein: Proteolytic processing, acylation, cell tropism, and detection of neutralizing antibodies
    H Ito; S Watanabe; A Takada; Y Kawaoka
    JOURNAL OF VIROLOGY, 75, 3, 1576, 1580, Feb. 2001, [Peer-reviewed]
    English, Scientific journal
  • Mucosal vaccination against influenza: Protection of pigs immunized with inactivated virus and ether-split vaccine
    YK Lim; A Takada; T Tanizaki; H Ozaki; K Okazaki; H Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 48, 4, 197, 203, Feb. 2001, [Peer-reviewed]
    English, Scientific journal
  • Mouse Mx2 protein inhibits hantavirus but not influenza virus replication
    HK Jin; K Yoshimatsu; A Takada; M Ogino; A Asano; J Arikawa; T Watanabe
    ARCHIVES OF VIROLOGY, 146, 1, 41, 49, 2001, [Peer-reviewed]
    English, Scientific journal
  • Global surveillance of animal influenza for the control of future pandemics
    H Kida; K Okazaki; A Takada; H Ozaki; M Tashiro; DK Lvov; KF Shortridge; RG Webster
    OPTIONS FOR THE CONTROL OF INFLUENZA IV, 1219, 169, 171, 2001, [Peer-reviewed]
    English, International conference proceedings
  • Downregulation of beta 1 integrins by Ebola virus glycoprotein: Implication for virus entry
    A Takada; S Watanabe; H Ito; K Okazaki; H Kida; Y Kawaoka
    VIROLOGY, 278, 1, 20, 26, Dec. 2000, [Peer-reviewed]
    English, Scientific journal
  • Functional importance of the coiled-coil of the Ebola virus glycoprotein
    S Watanabe; A Takada; T Watanabe; H Ito; H Kida; Y Kawaoka
    JOURNAL OF VIROLOGY, 74, 21, 10194, 10201, Nov. 2000, [Peer-reviewed]
    English, Scientific journal
  • Functional importance of the coiled-coil of the Ebola virus glycoprotein
    S Watanabe; A Takada; T Watanabe; H Ito; H Kida; Y Kawaoka
    JOURNAL OF VIROLOGY, 74, 21, 10194, 10201, Nov. 2000
    English, Scientific journal
  • Recognition of N-glycolylneuraminic acid linked to galactose by the alpha 2,3 linkage is associated with intestinal replication of influenza A virus in ducks
    T Ito; Y Suzuki; T Suzuki; A Takada; T Horimoto; K Wells; H Kida; K Otsuki; M Kiso; H Ishida; Y Kawaoka
    JOURNAL OF VIROLOGY, 74, 19, 9300, 9305, Oct. 2000, [Peer-reviewed]
    English, Scientific journal
  • 26.マウスのインターフェロン誘導性抗ウイルス遺伝子Mxに関する研究
    陳 喜慶; 高田 礼人; 森松 組子; 荻野 倫子; 有川 二郎; 渡辺 智正
    日本疾患モデル学会記録, 16, 33, 33, 公益社団法人 日本実験動物学会, 2000
    Japanese
  • Avian influenza virus intranasally inoculated infects the central nervous system of mice through the general visceral afferent nerve
    K Shinya; A Shimada; T Ito; K Otsuki; T Morita; H Tanaka; A Takada; H Kida; T Umemura
    ARCHIVES OF VIROLOGY, 145, 1, 187, 195, 2000, [Peer-reviewed]
    English, Scientific journal
  • Precursor genes of future pandemic influenza viruses are perpetuated in ducks nesting in Siberia
    K Okazaki; A Takada; T Ito; M Imai; H Takakuwa; M Hatta; H Ozaki; T Tanizaki; T Nagano; A Ninomiya; VA Demenev; MM Tyaptirganov; TD Karatayeva; SS Yamnikova; DK Lvov; H Kida
    ARCHIVES OF VIROLOGY, 145, 5, 885, 893, 2000, [Peer-reviewed]
    English, Scientific journal
  • Structure of the infected cell protein 0 gene of canine herpesvirus
    M Miyoshi; M Takiguchi; J Yasuda; A Hashimoto; A Takada; K Okazaki; H Kida
    ARCHIVES OF VIROLOGY, 145, 8, 1715, 1723, 2000, [Peer-reviewed]
    English, Scientific journal
  • Transcriptional activation of JC virus (JCV) by human T-lymphotropic virus type I (HTLV-I) tax protein in human neuronal cell lines.
    Okada Y; Sawa H; Tanaka S; Takada A; Suzuki S; Hasegawa H; Umemura T; Fujisawa J-i; Tanaka Y; Hall WW; Nagashima K
    J Biol Chem, 275, 22, 17016, 17023, 2000, [Peer-reviewed]
    English, Okada Y, Sawa H*, Tanaka S, Takada A, Suzuki S, Hasegawa H, Umemura T, Fujisawa J-i, Tanaka Y, Hall WW, Nagashima1 K: Transcriptional activation of JC virus (JCV) by human T-lymphotropic virus type I (HTLV-I) tax protein in human neuronal cell lines. J Biol Chem, 275, 17016-17023, 2000 (* corresponding author)*
  • Avirulent avian influenza virus as a vaccine strain against a potential human pandemic
    A Takada; N Kuboki; K Okazaki; A Ninomiya; H Tanaka; H Ozaki; S Itamura; H Nishimura; M Enami; M Tashiro; KF Shortridge; H Kida
    JOURNAL OF VIROLOGY, 73, 10, 8303, 8307, Oct. 1999
    English, Scientific journal
  • Induction of antibodies in mice by a recombinant baculovirus expressing pseudorabies virus glycoprotein B in mammalian cells
    H Aoki; Y Sakoda; K Jukuroki; A Takada; H Kida; A Fukusho
    VETERINARY MICROBIOLOGY, 68, 3-4, 197, 207, Aug. 1999, [Peer-reviewed]
    English, Scientific journal
  • Protective effects of intranasal vaccination with plasmid encoding pseudorabies virus glycoprotein B in mice
    A Takada; K Okazaki; H Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 47, 1-2, 25, 33, Aug. 1999, [Peer-reviewed]
    English, Scientific journal
  • Identification of the murine Mx2 gene: Interferon-induced expression of the Mx2 protein from the feral mouse gene confers resistance to vesicular stomatitis virus
    HK Jin; A Takada; Y Kon; O Haller; T Watanabe
    JOURNAL OF VIROLOGY, 73, 6, 4925, 4930, Jun. 1999, [Peer-reviewed]
    English, Scientific journal
  • Detection of canine herpesvirus DNA in the ganglionic neurons and the lymph node lymphocytes of latently infected dogs
    M Miyoshi; Y Ishii; M Takiguchi; A Takada; J Yasuda; A Hashimoto; K Okazaki; H Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 61, 4, 375, 379, Apr. 1999, [Peer-reviewed]
    English, Scientific journal
  • Detection of Canine Herpesvirus DNA in the Ganglionic Neurons and the Lymph Node Lymphocytes of Latently Infected Dogs
    Masahiro Miyoshi; Yuki Ishii; Mitsuyoshi Takiguchi; Ayato Takada; Jun Yasuda; Akira Hashimoto; Katsunori Okazaki; Hiroshi Kida
    Journal of Veterinary Medical Science, 61, 4, 375, 379, Apr. 1999, [Peer-reviewed]
    English, Scientific journal
  • Detection of Canine Herpesvirus DNA in the Ganglionic Neurons and the Lymph Node Lymphocytes of Latently Infected Dogs
    MIYOSHI Masahiro; ISHII Yuki; TAKIGUCHI Mitsuyoshi; TAKADA Ayato; YASUDA Jun; HASHIMOTO Akira; OKAZAKI Katsunori; KIDA Hiroshi
    The Journal of veterinary medical science, 61, 4, 375, 379, Japanese Society of Veterinary Science, Apr. 1999
    English, To determine the site of latent infection of canine herpesvirus (CHV), tissues from dogs convalescent from acute infection with CHV were examined for the presence of viral genome DNA by the nested polymerase chain reaction. CHV DNA was detected in the trigeminal ganglia and the retropharyngeal lymph nodes. In situ hybridization study of the tissues revealed that CHV genome persisted in the nuclei of ganglionic neurons and lymphocytes.
  • Antigenic and genetic analyses of H5 influenza viruses isolated from ducks in Asia
    M Imai; A Takada; K Okazaki; H Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 46, 4, 171, 177, Feb. 1999
    English, Scientific journal
  • Structure of the immediate early gene of canine herpesvirus - Brief report
    M Miyoshi; M Takiguchi; J Yasuda; A Hashimoto; A Takada; K Okazaki; H Kida
    ARCHIVES OF VIROLOGY, 144, 2, 407, 420, 1999, [Peer-reviewed]
    English, Scientific journal
  • Characterization of avian H5N1 influenza viruses from poultry in Hong Kong
    KF Shortridge; NN Zhou; Y Guan; P Gao; T Ito; Y Kawaoka; S Kodihalli; S Krauss; D Markwell; KG Murti; M Norwood; D Senne; L Sims; A Takada; RG Webster
    VIROLOGY, 252, 2, 331, 342, Dec. 1998, [Peer-reviewed]
    English, Scientific journal
  • Changes in H3 influenza A virus receptor specificity during replication in humans
    K Ryan-Poirier; Y Suzuki; WJ Bean; D Kobasa; A Takada; T Ito; Y Kawaoka
    VIRUS RESEARCH, 56, 2, 169, 176, Aug. 1998, [Peer-reviewed]
    English, Scientific journal
  • An attenuation mechanism of Newcastle disease vaccine strain TCND
    H Takakuwa; T Ito; A Takada; K Okazaki; H Kida
    ARCHIVES OF VIROLOGY, 143, 6, 1129, 1143, 1998, [Peer-reviewed]
    English, Scientific journal
  • Cloning, tissue distribution, and functional expression of two novel rabbit cytochrome P450 isozymes, CYP2D23 and CYP2D24
    Yukio Yamamoto; Mayumi Ishizuka; Ayato Takada; Shoichi Fujita
    Journal of Biochemistry, 124, 3, 503, 508, Japanese Biochemical Society, 1998, [Peer-reviewed]
    English, Scientific journal
  • A system for functional analysis of Ebola virus glycoprotein
    A Takada; C Robison; H Goto; A Sanchez; KG Murti; MA Whitt; Y Kawaoka
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 94, 26, 14764, 14769, Dec. 1997, [Peer-reviewed]
    English, Scientific journal
  • The cysteine residues of the M2 protein are not required for influenza A virus replication
    MR Castrucci; M Hughes; L Calzoletti; Donatelli, I; K Wells; A Takada; Y Kawaoka
    VIROLOGY, 238, 1, 128, 134, Nov. 1997, [Peer-reviewed]
    English, Scientific journal
  • Differences in sialic acid-galactose linkages in the chicken egg amnion and allantois influence human influenza virus receptor specificity and variant selection
    T Ito; Y Suzuki; A Takada; A Kawamoto; K Otsuki; H Masuda; M Yamada; T Suzuki; H Kida; Y Kawaoka
    JOURNAL OF VIROLOGY, 71, 4, 3357, 3362, Apr. 1997, [Peer-reviewed]
    English, Scientific journal
  • Protective immune response of chickens against Newcastle disease, induced by the intranasal vaccination with inactivated virus
    A Takada; H Kida
    VETERINARY MICROBIOLOGY, 50, 1-2, 17, 25, May 1996, [Peer-reviewed]
    English, Scientific journal
  • PERPETUATION OF INFLUENZA-A VIRUSES IN ALASKAN WATERFOWL RESERVOIRS
    T ITO; K OKAZAKI; Y KAWAOKA; A TAKADA; RG WEBSTER; H KIDA
    ARCHIVES OF VIROLOGY, 140, 7, 1163, 1172, 1995, [Peer-reviewed]
    English, Scientific journal
  • INDUCTION OF PROTECTIVE ANTIBODY-RESPONSES AGAINST PSEUDORABIES VIRUS BY INTRANASAL VACCINATION WITH GLYCOPROTEIN-B IN MICE
    A TAKADA; H KIDA
    ARCHIVES OF VIROLOGY, 140, 9, 1629, 1635, 1995, [Peer-reviewed]
    English, Scientific journal
  • ACQUISITION OF PATHOGENICITY OF A NEWCASTLE-DISEASE VIRUS ISOLATED FROM A JAPANESE-QUAIL BY INTRACEREBRAL PASSAGE IN CHICKENS
    MA ISLAM; T ITO; H TAKAKUWA; A TAKADA; C ITAKURA; H KIDA
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 42, 3-4, 147, 156, Dec. 1994, [Peer-reviewed]
    English, Scientific journal
  • PROTECTION OF MICE AGAINST AUJESZKYS-DISEASE VIRUS-INFECTION BY INTRANASAL VACCINATION WITH INACTIVATED VIRUS
    A TAKADA; Y SHIMIZU; H KIDA
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 56, 4, 633, 637, Aug. 1994, [Peer-reviewed]
    English, Scientific journal
  • Potentially virulent Newcastle disease viruses are maintained in migratory waterfowl populations.
    Takakuwa H; Ito T; Takada A; Okazaki K; Kida H
    Japanese Journal of Veterinary Research, 45, 207, 215, [Peer-reviewed]
    English, Scientific journal
■ Other Activities and Achievements
■ Books and other publications
■ Lectures, oral presentations, etc.
  • High exposure to Bas-Congo virus among Mangala residents 13 years after the Bas-Congo virus-associated acute hemorrhagic fever outbreak in the Democratic Republic of the Congo
    Ayato Takada
    U.S.-Japan Cooperative Medical Sciences Program (USJCMSP) International Conference on Emerging Infectious Diseases (EID) in the Pacific Rim, 06 Mar. 2024, English, Nominated symposium
    [Invited]
  • Niemann-Pick C1 heterogeneity controlling filovirus tropism to bat cells
    Ayato Takada
    U.S.-Japan Cooperative Medical Sciences Program (USJCMSP) International Conference on Emerging Infectious Diseases (EID) in the Pacific Rim, 08 Mar. 2024, English, Nominated symposium
    2024, [Invited]
  • フィロウイルス研究の最近の話題
    高田礼人
    第6回鹿児島大学感染症制御のためのシンポジウム, 27 Jan. 2023, Public symposium
    [Invited]
  • ウイルス性出血熱
    高田礼人
    第97回日本感染症学会総会・学術講演会, 30 Apr. 2023, Japanese, Nominated symposium
    2023, [Invited]
  • 抗体依存性感染増強
    高田礼人
    令和4 年度「感染・免疫・がん・炎症」全国共同研究拠点シンポジウム, 29 Mar. 2023, Japanese, Public discourse
    2023, [Invited]
  • フィロウイルス感染症
    高田礼人
    第166回日本獣医学会学術集会 シンポジウム 「エムポックス(サル痘)とサルが関与する人獣共通感染症」, 05 Sep. 2023, Japanese, Nominated symposium
    2023 - 2023, [Invited]
  • Niemann-Pick C1 heterogeneity controlling filovirus tropism to bat cells
    Ayato Takada
    10th International Filovirus Symposium, 21 Sep. 2022, English, Invited oral presentation
    18 Sep. 2022 - 21 Sep. 2022, 13358284, [Invited]
  • 何故 H5 および H7 亜型のウイルスだけが高病原性鳥インフルエンザウイルスになるのか
    髙田 礼人
    令和3年度「感染・免疫・がん・炎症」全国共同研究拠点シンポジウム, 28 Mar. 2022, Japanese, Nominated symposium
    [Invited]
  • The importance and issues of collaboration during R&D period for infectious disease control in Africa
    Ayato Takada
    AMED International Joint Symposium 2021, 01 Nov. 2021, English, Nominated symposium
    [Invited]
  • ウイルスは悪者か
    髙田 礼人
    経団連フォーラム21, 26 Oct. 2021, Japanese, Public discourse
    [Invited]
  • Viral Zoonosis and Global Surveillance
    Ayato Takada
    Third Country Training Program (Online) PREPARE for Emerging and Re-emerging Infectious Diseases in Southern Africa Region, 13 Oct. 2021, English, Public discourse
    [Invited]
  • JICA SATREPS ザンビア・コンゴにおける人獣共通感染症対策の成果と課題
    髙田礼人
    環境省タンザニア気候変動適応事業設計, 12 May 2021, Japanese, Public discourse
    [Invited]
  • Filovirus research: VSV Pseudotype and antibody
    Ayato Takada
    J-Rapid/eAsia Joint Symposium Power of Natural Products, 16 Mar. 2021, English, Invited oral presentation
    [Invited]
  • ウイルス性新興感染症の制御を目指して
    髙田礼人
    第16回北海道HIV/AIDS歯科医療研究会, 20 Feb. 2021, Japanese, Invited oral presentation
    [Invited]
  • ウイルスは悪者か
    髙田礼人
    ブンナビ薬学特別企画 対談シリーズ, 12 Dec. 2020, Japanese, Public discourse
    [Invited]
  • フィロウイルス研究における最近の知見
    髙田礼人
    第162回日本獣医学会学術集会, 10 Sep. 2019, Japanese, Invited oral presentation
    [Invited]
  • エボラおよびマールブルグ出血熱
    髙田礼人
    第8回日本精神科医学会学術集会, 05 Jul. 2019, Japanese, Invited oral presentation
    [Invited]
  • フィロウイルスに対する細胞の感受性とウイルスレセプターの多形
    高田 礼人
    「感染・免疫・がん・炎症」シンポジウム, 27 Mar. 2019, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • Toward the Control of Zoonoses
    TAKADA Ayato
    Nagasaki University WISE Symposium, 09 Mar. 2019, English
    [Invited], [International presentation]
  • Toward the control of viral zoonoses: Our SATREPS activity in Africa
    TAKADA Ayato
    The 59th Annual Meeting for the Japanese Society of Tropical Medicine, 10 Nov. 2018, English, Invited oral presentation
    [Invited], [Domestic Conference]
  • Update Ebola Virus Research
    TAKADA Ayato
    Studium Generale 3, Disease Control of the Wildlife-Livestock-Human Interface: Series, 05 Jul. 2018, English, Invited oral presentation
    [Invited], [Domestic Conference]
  • エボラウイルス研究最前線
    高田 礼人
    第20回日本医療マネジメント学会学術総会, 08 Jun. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Recent Topics from Ebola virus Research
    TAKADA Ayato
    Inner Mongolia Agriculture University Seminar, 18 Apr. 2018, English, Invited oral presentation
    [Invited], [International presentation]
  • Filoviruses
    TAKADA Ayato
    第91回日本細菌学会総会 シンポジウム, 26 Mar. 2018, English, Invited oral presentation
    [Invited], [Domestic Conference]
  • エボラウイルス感染症における新知見
    高田 礼人
    第66回日本感染症学会東日本地方会学術集会, 01 Nov. 2017, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 鳥インフルエンザの基礎とグローバルサーベイランス
    高田 礼人
    テニュアトラック推進機構主催セミナー 鳥インフルエンザと渡り鳥の関わり, 20 Oct. 2017, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 鳥インフルエンザウイルスHA開裂部位への塩基性アミノ酸挿入機構
    高田 礼人
    第31回インフルエンザ研究者交流の会シンポジウム, 09 Jun. 2017, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • Ebolavirus --Ecology and antiviral strategies--
    TAKADA Ayato
    11th Annual Meeting of Korean Society of Zoonosis, 19 May 2017, English, Keynote oral presentation
    [Invited], [International presentation]
  • エボラウイルス研究の最前線
    高田 礼人
    第32回日本環境感染学会総会学術集会 シンポジウム16 エボラウイルス病の最前線, 25 Jan. 2017, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • エボラウイルス研究の最前線
    高田 礼人
    ICD講習会, 25 Oct. 2016, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • Neutralization and Antibody-Dependent Enhancement of Ebolavirus
    TAKADA Ayato
    8th International Global Virus Network Meeting, 25 Oct. 2016, English, Invited oral presentation
    [Invited], [International presentation]
  • グローバルヘルスを支える生化学 エボラウイルスの診断・治療法開発の最前線
    高田 礼人
    第89回日本生化学会大会, 25 Sep. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Ebolavirus Entry into Cells --- Neutralization and Antibody-Dependent Enhancement---
    高田 礼人
    The 15th Awaji International Forum on Infection and Immunity, 09 Sep. 2016, English, Invited oral presentation
    [Invited], [International presentation]
  • 人獣共通感染症としてのインフルエンザ
    高田 礼人
    第24回呼吸器疾患・感染症研究会, 20 Jul. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 人獣共通感染症の研究最前線 -エボラ出血熱-
    高田 礼人
    日本麻酔科学会第63回学術集会, 26 Apr. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • エボラウイルス研究の最前線
    高田 礼人
    第90回日本感染症学会総会・学術講演会, 16 Apr. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 人獣共通感染症研究最前線 -エボラ出血熱とインフルエンザ-
    高田 礼人
    第45回野依フォーラム例会, 15 Apr. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • ウイルスの生態
    高田 礼人
    人間文化研究機構広領域連携型基幹研究プロジェクト キックオフ・シンポジウム, 19 Mar. 2016, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • A Monoclonal Antibody Neutralizing All Known Ebola Viruses
    TAKADA Ayato
    2016 US–Japan Annual Medical Biodefense Research Symposium Theme: “Ebola And Emerging Pathogens”, 14 Jan. 2016, English, Invited oral presentation
    [Invited], [International presentation]
  • フィロウイルスの細胞侵入機構
    高田 礼人
    平成27年度 遺伝子病制御研究所研究集会 感染・免疫・炎症・発癌, 18 Dec. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Ebolavirus: ecology and antiviral strategies
    TAKADA Ayato
    3rd GRF One Health Summit 2015, 05 Oct. 2015, English, Nominated symposium
    [Invited], [International presentation]
  • エボラウイルスとは
    高田 礼人
    第15回日本ハ-イオセーフティ学会総会, 15 Sep. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • エボラウイルス研究の現状と展望
    高田 礼人
    第32回医学情報サービス研究大会, 18 Jul. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • エボラ出血熱
    高田 礼人
    第62回日本実験動物学会総会, 28 May 2015, Japanese, Public symposium
    [Invited], [Domestic Conference]
  • フィロウイルス研究の現状と展望
    高田 礼人
    第33回川内カンファレンス, 30 Apr. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • エボラ出血熱:現状と研究の最前線
    高田 礼人
    岐阜大学市民講座, 02 Mar. 2015, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • 人獣共通感染症 特にエボラ出血熱について
    高田 礼人
    平成26年度 鳥取県獣医師会東部支部総会, 24 Feb. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • エボラウイルスに迫る
    高田 礼人
    北海道大学 創成研究機構第 12 回 創成シンポジウム 感染症研究の最前線 ― エボラ・結核を例に―, 24 Feb. 2015, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • Comparison of antiviral activity between IgA and IgG specific to influenza virus hemagglutinin: Increased potential of IgA for heterosubtypic immunity
    TAKADA Ayato
    "Improving Efficacy of Vaccines for ARI", Acute Respiratory Infections (ARI) Panel Meeting, 17th International Conference on Emerging Infectious Diseases (EID) in the Pacific Rim Emerging Viral Diseases, United States–Japan Cooperative Medical Sciences Pr, 28 Jan. 2015, English, Nominated symposium
    [Invited], [International presentation]
  • エボラウイルス研究とBSL4
    高田 礼人
    第十二回 日本防護服研究会 学術総会, 19 Jan. 2015, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • エボラおよびマールブルグウイルスによる感染症
    高田 礼人
    平成26年度新型インフルエンザ等新興・再興感染症研究推進事業シンポジウム, 15 Jan. 2015, Japanese, Public discourse
    [Domestic Conference]
  • エボラウイルスの基礎と最新知見
    高田 礼人
    第11回 群馬感染症研究会学術講演会, 17 Dec. 2014, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • エボラウイルス -研究の現状と展望-
    高田 礼人
    第200回 医学セミナー, 01 Oct. 2014, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • Infection and pathogenicity of Ebola virus and Biosafety
    TAKADA Ayato
    Laboratory Biosafety and Infection Control of Emerging Infectious Diseases, 05 Sep. 2014, English, Public discourse
    [Invited], [International presentation]
  • 北海道大学ザンビア拠点での取り組み
    高田 礼人
    J-GRID市民公開講演会「いま話題の感染症-SFTS、MERS、エボラ出血熱」, 23 Aug. 2014, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • エボラ出血熱とBSL-4
    高田 礼人
    長崎大学熱帯医学研究所 「市民公開特別講座」, 21 Aug. 2014, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • ホットゾーン的ウイルス研究とバイオセーフティーレベル4
    高田 礼人
    第8回細菌学若手コロッセウム, 06 Aug. 2014, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Comparison of antiviral activity between IgA and IgG
    TAKADA Ayato
    XVI International Congress of Virology, 28 Jul. 2014, English, Oral presentation
    [International presentation]
  • 鳥インフルエンザの基礎
    高田 礼人
    第12回インフルエンザ夏季セミナー, 20 Jul. 2014, Japanese, Invited oral presentation
    [Domestic Conference]
  • フィロウイルス感染症に対する防御免疫における抗体の役割
    高田 礼人
    第79回インターフェロン・サイトカイン学会, 20 Jun. 2014, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • Role of antibodies in protective immunity against filovirus infection
    TAKADA Ayato
    6th International Symposium on Filoviruses, 02 Apr. 2014, English, Oral presentation
    [Invited], [International presentation]
  • H7N9株やH5N1株を含めた新たなインフルエンザパンデミックの可能性について
    高田 礼人
    化血研KIKUCHIバイオセミナー「三風会」, 17 Jan. 2014, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 鳥インフルエンザ
    高田 礼人
    平成25年度家畜保健衛生所病性鑑定技術検討会, 18 Dec. 2013, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • フィロウイルス感染症
    高田 礼人
    第61回日本ウイルス学会学術集会, 12 Nov. 2013, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • Ecology of Avian Influenza Viruses: Topics from surveillance in Asia and Africa
    TAKADA Ayato
    1st Kyoto International Symposium on Virus-Host Coevolution, 07 Nov. 2013, English, Nominated symposium
    [Invited], [International presentation]
  • フィロウイルスの病原性と宿主域
    高田 礼人
    市民講座 やさしく学ぶ話題の感染症 -動物から人へうつる新たな病気-, 05 Oct. 2013, Japanese, Public discourse
    [Invited], [Domestic Conference]
  • Recent advances in filovirus research: Epidemiology and antiviral strategies
    TAKADA Ayato
    The 12th Awaji International Forum on Infection and Immunity, 13 Aug. 2013, English, Nominated symposium
    [Invited], [International presentation]
  • 「エボラ出血熱ウイルス」…糸のような形の、やさしそうで怖いウイルスの話
    高田 礼人
    みちのくウイルス塾, 13 Jul. 2013, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Recent Topics of Filovirus Research
    TAKADA Ayato
    International Conference in Medicine and Public Health 2013 (ICMPH2013) “Healthy Society beyond Frontiers”, 25 Jun. 2013, English, Nominated symposium
    [Invited], [International presentation]
  • Heterosubtypic antiviral activity of influenza virus hemagglutinin-specific antibodies
    TAKADA Ayato
    Fifteenth International Conference on Negative Strand Viruses, 20 Jun. 2013, English, Oral presentation
    [International presentation]
  • Activities of Hokkaido University Research Center for Zoonosis Control
    TAKADA Ayato
    Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD) 2013 Annual Meeting, 22 Apr. 2013, English, Nominated symposium
    [Invited], [International presentation]
  • Serological Survey of Antibodies to Filoviruses
    TAKADA Ayato
    6th U.S. - Japan Medical Biodefense Research Symposium, “New Frontiers in Medical Biodefense Research Between the United States and Japan”, 04 Feb. 2013, English, Nominated symposium
    [Invited], [International presentation]
  • Serological survey of antibodies to filoviruses in wild animals
    TAKADA Ayato
    Asian-African Research Forum on Emerging and Reemerging Infections 2013, 24 Jan. 2013, English, Nominated symposium
    [Invited], [International presentation]
  • 海外のBSL4 施設での実験の状況
    高田 礼人
    日本学術会議 公開シンポジウム, 14 Dec. 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • エボラおよびマールブルグウイルス
    高田 礼人
    第60回日本ウイルス学会学術集会 シンポジウム1 人獣共通感染症, 13 Nov. 2012, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • 人獣共通感染症としてのインフルエンザ
    高田 礼人
    第21回先端科学移動大学2012, Nov. 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • H5N1高病原性鳥インフルエンザウイルスと私との関わり
    高田 礼人
    第2回宮崎大学 鳥インフルエンザシンポジウム, 27 Oct. 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Serological evidence of filovirus infection in Indonesian orangutans
    TAKADA Ayato
    46th Joint Working Conference on Viral Diseases US-Japan Cooperative, Medical Science Program, 19 Jun. 2012, English, Nominated symposium
    [Invited], [International presentation]
  • Ebola and Marburg viruses
    TAKADA Ayato
    4th International Symposium of Animal Global Health, 31 May 2012, English, Invited oral presentation
    [Invited], [International presentation]
  • ウイルス感染と粘膜免疫
    高田 礼人
    日本薬学会第132年会 一般シンポジウムS29 鼻腔内投与による脳機能治療の可能性, 31 Mar. 2012, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • Ebola and Marburg viruses
    TAKADA Ayato
    Nagasaki Symposium on Emerging Viral Diseases, 21 Feb. 2012, English, Invited oral presentation
    [Invited], [International presentation]
  • エボラおよびマールブルグウイルス
    高田 礼人
    第7回霊長類医科学フォーラム, 18 Nov. 2011, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Influenza and Ebola viruses “Pathogenicity and Host Range”
    TAKADA Ayato
    ヤンセンファーマ株式会社 社内勉強会, 07 Sep. 2011, Japanese, Keynote oral presentation
    [Invited], [Domestic Conference]
  • Antibody-dependent enhancement of Marburg virus infection
    TAKADA Ayato
    45th Joint Working Conference on Viral Diseases US-Japan Cooperative, Medical Science Program, 22 Jun. 2011, English, Nominated symposium
    [Invited], [International presentation]
  • フィロウイルスの細胞侵入機構
    高田 礼人
    第58回日本ウイルス学会学術集会 シンポジウム10 ウイルスの細胞侵入, 09 Nov. 2010, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • 人獣共通感染症としてのインフルエンザ
    高田 礼人
    第19回先端科学移動大学2010, Nov. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 「人獣共通感染症」ウイルスはどうやって行きのびているのか
    高田 礼人
    長崎大学熱帯医学研究所市民公開特別講座, 26 Oct. 2010, Japanese, Keynote oral presentation
    [Invited], [Domestic Conference]
  • ウイルスの病原性と宿主域-人獣共通感染症としてのインフルエンザ
    高田 礼人
    第75回日本民族衛生学会, 26 Sep. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 人獣共通感染症としてのインフルエンザ
    高田 礼人
    第84回日本数理生物学会大会, 15 Sep. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Enzyme-linked immunosorbent assay for the detection of filovirus species-specific antibodies
    TAKADA Ayato
    44th Joint Working Conference on Viral Diseases US-Japan Cooperative, Medical Science Program, 28 Jun. 2010, English, Nominated symposium
    [Invited], [International presentation]
  • インフルエンザウイルスヘマグルチニン亜型間交差反応性抗体の解析
    高田 礼人
    第10回日本蛋白質科学会年会 ウィルス感染の分子機構とその制御, 17 Jun. 2010, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • インフルエンザウイルスの抗原変異予測と亜型間交差感染防制
    高田 礼人
    日本薬学会第13年回 一般シンポジウムS49 インフルエンザの制圧に向けた新しい挑戦, 28 Mar. 2010, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • エボラウイルスとインフルエンザウイルスを追いかけて
    高田 礼人
    公開シンポジウム 感染症の国際疫学研究の最前線―日本をとりまく感染症の現状―, 12 Dec. 2009, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Mechanisms of filovirus entry
    TAKADA Ayato
    Workshop Taiwan-Japan "Host-Pathogen Interaction", 16 Nov. 2009, English, Invited oral presentation
    [Invited], [International presentation]
  • 人獣共通感染症としてのインフルエンザ
    高田 礼人
    第4回抗菌化学療法研究会, 07 Nov. 2009, Japanese, Invited oral presentation
    [Invited]
  • 人獣共通感染症としてのインフルエンザ
    高田 礼人
    第47回全国大学保健管理研究集会, 17 Sep. 2009, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Different efficiency of C-type lectin-mediated entry between filoviruses
    TAKADA Ayato
    43rd Joint Working Conference on Viral Diseases, US-Japan Cooperative Medical Science Program, 22 Jul. 2009, English, Nominated symposium
    [Invited], [International presentation]
  • 人獣共通感染症の先回り戦略
    高田 礼人
    第55回日本ウイルス学会学術集会, Oct. 2008, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • インフルエンザウイルスの病原性と宿主域
    高田 礼人
    第11回北海道ウイルス感染症セミナーの会, 20 Sep. 2008, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • インフルエンザウイルスの病原性と宿主域
    高田 礼人
    自衛隊北部防衛衛生学会, 22 Jan. 2008, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Mission of Research Center for Zoonosis Control
    TAKADA Ayato
    日本の人獣共通感染症研究動向=AIとBSE=, 18 Oct. 2007, English, Keynote oral presentation
    [Invited], [International presentation]
  • エボラウイルスの病原性発現の分子基盤
    高田 礼人
    第27回日本医学会総会, 07 Apr. 2007, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • Epitopes required for antibody-dependent enhancement of Ebola virus infection
    Takada A; Ebihara H; Feldmann H; Kawaoka Y
    FILOVIRUSES:Recent Advances and Future Challenges, Sep. 2006, English, Poster presentation
    [International presentation]
  • エボラウイルスの感染、免疫、疫学
    高田 礼人
    人獣共通感染症 教育公開フォーラム, 22 Jul. 2006
  • Mechanisms of filovirus entry into cells
    Ayato Takada; Heinz Feldmann; Yoshihiro Kawaoka
    XIII International Conference on Negative Strand Viruses, 17 Jun. 2006, English, Oral presentation
    [International presentation]
  • インフルエンザという人獣共通感染症
    TAKADA Ayato
    International Symposium in Fukuoka - Coming Health Emergency: How Nurses Respond to Unknown Emerging Diseases, 03 Mar. 2006, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 平成17年度杉浦奨励賞受賞講演 「エボラウイルス表面糖蛋白質の機能解析」
    高田 礼人
    第53回日本ウイルス学会総会, 21 Nov. 2005, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Two different routes of antibody-dependent enhancement of Ebola virus infection
    TAKADA Ayato
    German-Japanese Symposium on Emerging and Reemerging Viruses, 14 May 2005, English, Invited oral presentation
    [Invited], [International presentation]
  • エボラウイルスの抗体依存性感染増強現象とエピトープ
    高田礼人; 海老原秀喜; 河岡義裕
    第52回日本ウイルス学会総会, 23 Nov. 2004, Japanese, Oral presentation
    [Domestic Conference]
  • エボラウイルスの感染初期課程:抗体およびレクチンによる感染増強現象
    高田礼人; 河岡義裕
    第51回日本ウイルス学会総会, 28 Oct. 2003, Japanese, Oral presentation
    [Domestic Conference]
  • エボラウイルスに対する中和抗体のエピトープの同定と受動免疫の感染防御効果
    高田礼人; Heinz Feldmann; 河岡義裕
    第50回日本ウイルス学会総会, 18 Oct. 2002, Japanese, Oral presentation
    [Domestic Conference]
  • Antibody-dependent enhancement of Ebola virus infection
    TAKADA Ayato
    Awaji International Forum on Infection and Immunity, 26 Aug. 2002, English, Invited oral presentation
    [Invited], [International presentation]
  • エボラウイルスにおける抗体依存性感染増強現象
    高田礼人; Heinz Feldmann; 渡辺真治; 河岡義裕
    第49回日本ウイルス学会総会, 14 Oct. 2001, Japanese, Oral presentation
    [Domestic Conference]
  • エボラウイルス表面糖蛋白の発現による細胞変性効果とインテグリンの発現抑制
    高田礼人; 岡崎克則; 喜田宏; 渡辺真治; 伊藤啓史; 河岡義裕
    第48回日本ウイルス学会総会, 14 Oct. 2000, Japanese, Oral presentation
    [Domestic Conference]
  • エボラウイルス表面糖蛋白もつG蛋白欠損VSVの作出と応用
    高田礼人; Anthony Sanchez; Michael A. Whitt; 喜田宏; 岡崎克則; 河岡義裕
    第45回日本ウイルス学会総会, 21 Sep. 1997, Japanese, Oral presentation
    [Domestic Conference]
  • エボラウイルス表面糖蛋白の機能解析 プラスミドによる発現とG蛋白欠失VSVの利用
    高田礼人; SANCHEZ A; WHITT M A; 喜田宏; 岡崎克則; 河岡義裕
    第124回日本獣医学会学術集会講演要旨集, 1997, Japanese, Oral presentation
    [Domestic Conference]
  • オーエスキー病ウイルスgII蛋白の点鼻接種によるマウスの感染防御
    高田礼人; 喜田宏
    第119回日本獣医学会学術集会, 1995, Japanese, Oral presentation
    [Domestic Conference]
  • 不活化ウイルスの鼻腔内接種によって誘導される抗体応答およびその感染防御効果
    高田礼人; 伊藤寿啓; 清水悠紀臣; 喜田宏
    第118回日本獣医学会学術集会, 1994, Japanese, Oral presentation
    [Domestic Conference]
■ Syllabus
  • 感染症学特別研究Ⅰ, 2024年, 博士後期課程, 国際感染症学院
  • 微生物学特論, 2024年, 博士後期課程, 獣医学院
  • 感染症学特別演習, 2024年, 博士後期課程, 国際感染症学院
  • 微生物学特論, 2024年, 博士後期課程, 国際感染症学院
  • 感染症学特別研究ⅡA, 2024年, 博士後期課程, 国際感染症学院
  • 人獣共通感染症制御学特論, 2024年, 博士後期課程, 国際感染症学院
  • 感染症学特別研究ⅡB, 2024年, 博士後期課程, 国際感染症学院
  • 人獣共通感染症対策専門特論, 2024年, 博士後期課程, 国際感染症学院
  • 人獣共通感染症学, 2024年, 学士課程, 獣医学部
  • 微生物学, 2024年, 学士課程, 医学部
■ Affiliated academic society
  • 日本ワクチン学会
  • 日本ウィルス学会
  • 日本獣医学会
  • American Society for Microbiology
■ Research Themes
  • Neglectedフィロウイルス感染症に対する抗体医薬開発
    科学研究費助成事業
    01 Apr. 2024 - 31 Mar. 2027
    高田 礼人
    日本学術振興会, 基盤研究(B), 北海道大学, 24K02283
  • Exploring Marine Natural Products that Regulate Dynamic Responses of cells
    Grants-in-Aid for Scientific Research
    01 Apr. 2022 - 31 Mar. 2025
    酒井 隆一; 高田 礼人; 田中 良和; 松井 崇; 松本 健; 八代田 陽子; 荒木 真理人
    抗ウイルス作用を指標として海綿よりHalistanol sulfate (HS)を得た。HSにはプロテアーゼ阻害作用が知られているが、それに加え、細胞内の脂質油症に関与し、膜コレステロールの蓄積を促進することを見いだし、HSは細胞の動的応答に関連する複数の経路で抗ウイルス作用を示すと示唆された。また、幅広い抗ウイルス作用を示す海綿より得られた化合物に翻訳阻害作用が確認され、特定の翻訳阻害機構が抗ウイルス作用につながることが示唆された。スナギンチャクより得られたKB343のターゲット解析では、小胞輸送に関与する複数のタンパク質が標的として見いだされた。KB343に抗ウイルス作用も確認され、KB343は、細胞に侵入した後、小胞輸送関連の応答を阻害することで活性を発揮している可能性が示唆された。KB343はアルギニン由来のC5N3ユニット3つで構成されるが今回、愛媛産のスナギンチャクより新規のC5N3ユニット4つで構成される化合物を見出した。この発見はスナギンチャクのC5N3生合成経路の解明する一助になるものと考えている。一方、ホヤから得られた神経活性成分メルパラジン・ドーパルジミン類の構造―活性相関を調べるとともに、抗ウイルス作用を探索したところメルパラジンCが弱い抗ウイルス作用を示した。また、サイトカイン受容体に作用する化合物の探索を進めたところ、海綿に含まれるポリカチオン化合物画分にTPO受容体活性化が確認された。一方、海綿には細胞内に侵入するタンパク質が存在するが、SORが得られた海綿より新規に細胞内侵入レクチン(SOR-L)を見出した。蛍光ラベル化SOR-Lは核に到達したがほとんど細胞毒性を示さなかった。同じく海綿のレクチンRASP-LのLC-MSを用いたアミノ酸配列解析を行い、最大20アミノ酸の内部配列を複数得ているが、既知のタンパク質との相同性は見られなかった。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23K23695
  • Structure-based functionalization of novel sugar-binding proteins derived from marine natural products for corona drug discovery
    Grants-in-Aid for Scientific Research
    01 Apr. 2022 - 31 Mar. 2025
    田中 良和; 高田 礼人; 酒井 隆一; 横山 武司; 松井 崇
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Tohoku University, 23K23519
  • 細胞の動的応答を制御する海洋天然物の探索
    科学研究費助成事業
    01 Apr. 2022 - 31 Mar. 2025
    酒井 隆一; 高田 礼人; 田中 良和; 松本 健; 八代田 陽子; 荒木 真理人
    日本学術振興会, 基盤研究(B), 北海道大学, 22H02430
  • Structure-based functionalization of novel sugar-binding proteins derived from marine natural products for corona drug discovery
    Grants-in-Aid for Scientific Research
    01 Apr. 2022 - 31 Mar. 2025
    田中 良和; 高田 礼人; 酒井 隆一; 横山 武司
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Tohoku University, 22H02252
  • フィロウイルスの宿主域・病原性・生態の解明と予防・治療・診断法の開発
    感染症研究革新イニシアティブ(J-PRIDE)
    Sep. 2017 - Mar. 2025
    高田 礼人
    日本医療研究開発機構(AMED), Principal investigator, Competitive research funding
  • マールブルグ出血熱に対する抗体医薬開発
    科学研究費助成事業 基盤研究(B)
    01 Apr. 2021 - 31 Mar. 2024
    高田 礼人
    エボラおよびマールブルグウイルスは、ヒトまたはサルに急性で致死率の高い感染症(エボラ出血熱およびマールブルグ出血熱)を引き起こす。現在までに承認された抗体医薬はエボラウイルス1種のみに特異的であり、マールブルグウイルスには全く効果が無い。本研究は、これまでエボラウイルスに対する抗体に関して得られた知見を基にして、ウイルスの細胞侵入に関わる特定のエピトープに着目することによって、マールブルグ出血熱に対して有効な抗体医薬の開発に資する事を目的とする。
    マールブルグウイルス(Angola株)の表面糖蛋白質(GP)の遺伝子をゲノム内に組み込んだ増殖性の水疱性口炎ウイルス(シュードタイプウイルス)に感染させ回復したマウスに、マールブルグウイルス(Angola株)のGPを持つウイルス様粒子を腹腔内投与してブーストした。そのマウスから脾臓を採取し、脾細胞とミエローマ細胞を融合させ、通常の方法でハイブリドーマの作出を試みた。その結果、調べたマールブルグウイルス株(Angola、MusokeおよびRavn)全てに交差中和活性を示すモノクローナルIgG抗体およびAngolaとMusoke株にのみ中和活性を示すIgG抗体が複数得られた。
    フィロウイルスのレセプターであるNPC1分子上のドメインC内に存在するloop構造(loop1およびloop2)を模した合成ペプチドをヒトNPC1のアミノ酸配列を基に設計した。これらのペプチドの中和活性を、非増殖性シュードタイプ水疱性口炎ウイルスを用いて解析した結果、阻害薬候補となるアミノ酸配列を見出した。
    日本学術振興会, 基盤研究(B), 北海道大学, 21H02734
  • Epidemiology of zoonotic virus infections in Africa
    Science and Technology Research Partnership for Sustainable Development
    Apr. 2018 - Mar. 2024
    TAKADA Ayato
    Japan Agency for Medical Research and Development, Principal investigator, Competitive research funding
  • Study for the development of Ebola hemorrhagic fever treatment
    Grants-in-Aid for Scientific Research
    01 Apr. 2016 - 31 Mar. 2021
    Takada Ayato
    Mouse monoclonal antibodies with cross-neutralizing activity against multiple ebolavirus species were generated. Detailed analyses of the epitopes recognized by the antibodies suggested that that some of the antibodies bind to the side region of the viral surface glycoprotein (GP) molecule and inhibit the membrane fusion between the cellular membrane and the virus envelope. Electron microscopic structural analysis of the complex of the GP molecule and Mab 6D6, one of the cross-reactive antibodies, revealed that this antibody recognizes the fusion loop region of GP. In addition, a novel compound having the ability to reduce the infectivity of all known ebolaviruses were obtained from an existing compound library. It was suggested that this compound binds to the side surface region of the GP molecule and inhibits the membrane fusion.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 16H02627
  • Development of universal antibody therapy for Ebola hemorrhagic fever
    Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    01 Apr. 2015 - 31 Mar. 2018
    Takada Ayato
    Ebolaviruses cause severe hemorrhagic fever (Ebola hemorrhagic fever) in humans and nonhuman primates. Five phylogenetically distinct species are currently known in the genus Ebolavirus and the antigenicity among these ebolavirus species is also largely different. This study attempted to establish procedures to induce neutralizing antibodies cross-reactive to all known ebolavirus species. Our data suggest the possibility that cross-reactive neutralizing antibodies can be induced more efficiently in mice immunized with virus-like particles using an immunosuppressive agent (rapamycin) or mice infected with replication competent vesicular stomatitis virus pseudotyped with ebolavirus glycoprotein than in mice immunized with virus-like particles using a standard adjuvant.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Principal investigator, Competitive research funding, 15K14851
  • フィロウイルスの細胞侵入メカニズムと宿主域に関する研究
    科学研究費助成事業 新学術領域研究(研究領域提案型)
    01 Apr. 2015 - 31 Mar. 2017
    高田 礼人
    ヒトNPC1の多様性とフィロウイルスに対する感受性:ヒト由来Jurkat TおよびRamos B細胞はいずれもフィロウイルスに対して非感受性である事が知られている。面白いことに、Jurkat T細胞は、フィロウイルスの細胞吸着因子の一つであるC型レクチンを発現させることによって感受性を獲得したのに対して、Ramos B細胞は非感受性のままであった。そこで、Jurkat TおよびRamos B細胞のNPC1遺伝子をクローニングし、アミノ酸配列を比較したところ、2箇所(200番目と215番目)のアミノ酸が異なる事が分かった。これらのNPC1をクローニングし強制発現させた細胞を確立し、Vesicular Stomatitis Virus (VSV)のシュードタイプシステムを用いて、フィロウイルスに対する感受性の違いを解析したが、違いは認められなかった。


    コウモリ由来細胞のフィロウイルスに対する感受性を決定する因子の探索:既知のフィロウイルス全てについて、GPを持つシュードタイプウイルスの感染性を様々なコウモリ由来の培養細胞で比較した結果、エボラウイルスは感染するがマールブルグウイルスは感染しないコウモリ細胞(FBKT1)が存在する事が明らかとなり、レセプター(NPC1)の違いによるものと推定された。FBKT1にヒト由来のNPC1を導入するとマールブルグウイルスに対する感受性を獲得した。マールブルグウイルス感受性細胞とFBKT1の間で、NPC1のアミノ酸配列を比較した結果、GPとの結合に重要と考えられている領域のアミノ酸配列に違いが認められた。また、NPC1との結合に重要と考えられているGP上のアミノ酸配列にもエボラウイルスとマールブルグウイルスの間で違いが認められた。これらのアミノ酸を入れ替えると感染性が逆転した。以上より、GPとNPC1の結合がフィロウイルスの宿主域に関与している事が示唆された。
    日本学術振興会, 新学術領域研究(研究領域提案型), 北海道大学, Principal investigator, Competitive research funding, 15H01249
  • Computational analysis of a conformational epitope of a broadly neutralizing antibody in influenza A virus hemagglutinin
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2013 - 31 Mar. 2017
    Igarashi Manabu; TAKADA AYATO
    The HA of influenza A viruses is classified into 16 subtypes (H1-H16). We have previously reported a cross-reactive antibody, designated S139/1, which neutralizes H1, H2, H3, H13, and H16 subtypes. In this study, we characterized the S139/1 recognition sites on different HAs by computational methods such as molecular modeling and dynamics simulations. We investigated the contribution of individual residues on each HA to the interaction with S139/1, and found that amino acids at 10 positions on HA strongly contributed to S139/1 binding as for the strains neutralized by S139/1. Analysis of hydrogen bond interactions emphasized that the residues at positions 156, 158 and 193 were the most important for S139/1 binding. Indeed, amino acid substitutions at these three positions were experimentally observed in the mutant viruses escaping from neutralization by S139/1. Thus, our computational methods identified the amino acid residues critical for the cross-neutralizing activity of S139/1.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 25450417
  • Cross-reactive antibodies to influenza virus hemagglutinins and their epitopes
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2012 - 31 Mar. 2017
    Takada Ayato; ITO Kimihito; IGARASHI Manabu; YOSHIDA Reiko; MURAMATSU Mieko; MIYAMOTO Hiroko; Wilson Ian
    By focusing on a novel antiviral function (budding inhibition), we found potential roles of anti-hemagglutinin antibodies in cross-protective immunity against influenza A viruses with multiple HA subtypes. It was particularly noted that the comparison between IgG and IgA antibodies recognizing the same epitope on the HA molecule clearly demonstrated the greater potential of HA-specific IgA than IgG antibodies in antiviral activities. It was also attempted to modify antibody specificity by structure-based molecular simulation and production of recombinant antibodies.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Principal investigator, Competitive research funding, 24390110
  • Surveillance of Viral Zoonoses in Africa
    Science and Technology Research Partnership for Sustainable Development
    Jun. 2012 - Mar. 2017
    TAKADA Ayato
    Japan Science and Technology Agency, Principal investigator, Competitive research funding
  • Predicting antigenic changes of influenza viruses using text data assimilation.
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2013 - 31 Mar. 2016
    Kimihito Ito; TAKADA Ayato; IGARASHI Manabu
    Human influenza viruses mutate from time to time, causing annual epidemics worldwide. Given the high mutation rate of the viral gene, influenza vaccine strains need to be updated every two to three years. In order to prepare an effective vaccine strain prior to each influenza season, we investigated text data assimilation methods that allow us to predict the evolution of viral amino acid sequences. As a result, we developed a mathematical model consisting of human herd immunity, the number of infections, and population of circulating vires. The model provides a mathematical basis of bioinformatics methods to prepare an effective vaccine strain prior to influenza seasons.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 25280080
  • Mechanism of IgA-mediated cross protection induced by mucosal immunization
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2013 - 31 Mar. 2016
    YOSHIDA Reiko; TAKADA Ayato
    Mucosal immunization with influenza virus vaccine confers cross-protection against infection with influenza virus antigenic variants as well as multiple subtypes of influenza A viruses. In this study, we found that many cross-reactive but non-neutralizing anti-HA IgA antibodies are produced in the upper respiratory tract of immunized mice. These anti-HA IgA antibodies showed stronger antiviral activities against influenza A viruses than IgG antibodies. Particularly, the results from this study suggest that the inhibition of virus particles release from the infected cell surface may be one of the IgA-mediated protective mechanisms important for heterosubtypic immunity.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 25450418
  • フィロウイルスの宿主域と受容体に関する研究
    科学研究費助成事業 新学術領域研究(研究領域提案型)
    01 Apr. 2013 - 31 Mar. 2015
    高田 礼人
    フィロウイルス科に属するエボラおよびマールブルグウイルスはヒトを含む霊長類に重篤な出血熱をひきおこす病原体として知られている。しかし、人獣共通感染症病原体であるフィロウイルスの宿主特異性あるいは宿主域を決定する分子基盤に関する知見は殆どない。本研究では、ウイルスのtropism決定の第一因子である細胞侵入過程(吸着・膜融合)に着目し、フィロウイルスの宿主域決定メカニズムに関する基礎的知見を得ることを目的とする。
    フィロウイルスの細胞吸着に関与する宿主分子の一つであるT-cell immunoglobulin and mucin domain 1 (TIM-1)に対するマウスモノクローナル抗体M224/1がフィロウイルスの細胞侵入を阻害する事を見出した。蛍光標識したウイルス様粒子(VLP)を用いて、M224/1存在下および非存在下で吸着・取り込み・膜融合を定量的に比較解析した結果、M224/1存在下でのVLPの吸着阻害効果は僅かであるが、VLPとエンドソーム膜との膜融合が著しく阻害された。興味深い事に、TIM-1はNiemann-Pick C1 (NPC1:フィロウイルスの膜融合に必須な宿主分子)はVero E6細胞内小胞において共局在し、両者は小胞内で結合していた。さらに、細胞内のTIM-1/NPC1複合体と膜融合を起こしているVLPの局在は一致した。以上の結果は、フィロウイルスはTIM-1を介して細胞表面に吸着した後、TIM-1と共に細胞内に取り込まれ、後期エンドソーム/リソソームにおいて、TIM-1とNPC1との結合を経て膜融合が起こることを示唆する。さらに、M224/1はTIM-1とNPC1との相互作用を阻害することによって、膜融合を阻害することが示された。
    日本学術振興会, 新学術領域研究(研究領域提案型), 北海道大学, Principal investigator, Competitive research funding, 25115501
  • Antibody-mediated inhibition of filovirus budding
    Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    01 Apr. 2012 - 31 Mar. 2014
    TAKADA Ayato; ITO Kimihito; IGARASHI Manabu
    Monoclonal antibodies (MAbs) specific to Marburg virus glycoprotein (GP) were produced to analyze their activity to suppress the virus budding. We found that some of the MAbs, which did not have a classical neutralizing activity, efficiently inhibited the budding and release of MARV particles from infected cells. A couple of escape variants selected by these MAbs had deletions of the mucin-like region in GP or single amino acid substitutions in the furin-recognition motif in GP. These results demonstrate a novel mechanism of antibody-mediated inhibition of MARV budding and the extraordinary structural flexibility and variability of MARV GP to escape from immunological pressure of antibodies.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Principal investigator, Competitive research funding, 24658252
  • インフルエンザウイルスの異種宿主間伝播に関与する細胞因子の研究
    科学研究費助成事業 特別研究員奨励費
    2010 - 2012
    高田 礼人; MANZOOR Rashid
    オルソミクスウイルス科に属するA型インフルエンザウイルスは様々な鳥類および哺乳類に感染する人獣共通感染症病原体である。その宿主域を決定する因子についてはこれまでに数多くの報告がなされている。それら因子のうちのいくつかは、宿主域のみならずウイルスの病原性をも決定することが知られている。しかしながら、ウイルスが宿主細胞へ侵入した後、それら因子がどのような宿主因子と相互作用し、どのようにウイルスの宿主域や病原性に関与しているのかを説明する知見はほとんど見られない。本研究は、これまで解明できなかったインフルエンザウイルスポリメラーゼ蛋白質と宿主因子の相互作用に関する様々な新しい知見を得ることを目的とする。
    FLAGタグをC末端あるいはN末端に付した組換えインフルエンザウイルス(HK483およびHK486株)ポリメラーゼ蛋白質(PB2、PB1およびPA蛋白質)を単独で発現するプラスミドを293T細胞に導入し、可溶化後、抗FLAGタグ抗体ビーズを用いて免疫沈降した。SDS-PAGEで展開した結果、幾つかの宿主由来蛋白質バンドが確認された。これらのバンドを資料分析によって解析した結果、宿主蛋白質であるHsp70およびhnRNP等であることが判明した。これらの蛋白質はポリメラーゼと相互作用する因子である可能性が高い。共焦点顕微鏡を用いた観察によって、ポリメラーゼとこれらの宿主蛋白質は細胞内で共局在することが明らかとなった。HK483およびHK486株以外のインフルエンザAウイルスでの同様の現象が認められた。特にPB2蛋白質との相互作用が重要であった。さらに、siRNAを用いてHsp70をノックダウンした細胞(293TおよびHera細胞)では、インフルエンザウイルスの増殖が抑えられることを見出した。また、各種ストレスによって細胞内に核内に誘導されるHsp70発現とウイルス増殖効率の間に相関があることを見出した。
    以上の結果は、Hsp70はインフルエンザAウイルスの増殖効率を高める宿主因子であることを示唆している。
    日本学術振興会, 特別研究員奨励費, 北海道大学, 10F00109
  • Antibody therapy against novel influenza virus infection using anImmunosuppressed non-human primate model
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2010 - 2012
    ITOH Yasushi; OGASAWARA Kazumasa; ITO Mutsumi; TAKADA Ayato
    The purpose of this study is development of anti-influenza virus drugs that are effective under the immunocompromised condition.We developed human-mouse chimeric anti-influenza virus hemagglutinin antibody with neutralizing activity. Administration of the antibody to immunosuppressed cynomolgus macaques improved survival rates in highly pathogenic avian influenza virus infection, whereas immunosuppressed macaques without the treatment showed severe symptoms. It is expected that the therapy with the developed anti-hemagglutinin antibody would be effective in immunocompromised influenza patients as confirmed in the immunosuppressed macaquemodel.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Shiga University of Medical Science, 22390076
  • Studies on cross-reactive antibodies to multiple subtypes of influenza virus henagglutinin induced by mucosal immunization
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2009 - 2011
    TAKADA Ayato; SUZUKI Yasuhiko; ITO Kimihito
    Currently used parenteral influenza vaccines induce serum IgG antibody response against hemagglutinin (HA), but do not protect primary infection in the respiratory tissues. In addition, vaccine-induced antibodies are not cross-reactive to viruses with different HA subtypes from that of vaccine strains. In this study, we found that intranasal immunization of mice with inactivated influenza viruses induced antibodies cross-reactive to multiple HA subtypes. Furthermore, it was suggested that IgA antibodies associated with mucosal immunity played an important role in heterosubtypic inhibition of virus replication.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Principal investigator, Competitive research funding, 21390134
  • インフルエンザウイルスのRNA分節間に形成される塩基対の検索
    科学研究費助成事業 挑戦的萌芽研究
    2009 - 2010
    伊藤 公人; 高田 礼人
    本研究では、公共データベースに蓄積された大量のウイルスゲノムを計算機を用いて解析することにより、RNA分節の選択的集合を説明し得る塩基対の構造を網羅的に探索することを目的とする。平成22年度は、下記項目に関して研究を行った。1.RNA分節において、塩基が極度に保存されている位置を明らかにする従来研究の成績からパッケージングシグナルは、各RNA分節のから5'末端および3'末端付近の領域に存在することが示唆されている。パンデミック2009インフルエンザウイルス(H1N1)の2285株分の塩基配列をNCBIから取得し、平均情報量を指標に各RNA分節において塩基が極度に保存されている領域を検索した。その結果、ほとんど全てのRNA分節において、3'末端付近の領域に塩基置換が見られた。2.二つのRNA分節で同時に変異する傾向にある塩基対があるか否かを確認する二つのRNA分節で同時に変異する傾向にある塩基対を高速に検索するために、同時エントロピーの比を用いる手法を開発した。同法を用いて、パンデミック2009インフルエンザウイルス(H1N1)のRNA分節間で同時に変異している塩基を探索した。その結果、PB2の95番目とNPの1530番目、PB2の573番目とNPの44番目、PB1の288番目とHAの1715番目、PAの64番目とNPの417番目、PAの64番目とNPの1419番目、NPの32...
    日本学術振興会, 挑戦的萌芽研究, 北海道大学, Coinvestigator not use grants, Competitive research funding, 21650067
  • 抗体依存性感染増強現象を利用したアジュバントの開発
    科学研究費助成事業 挑戦的萌芽研究
    2008 - 2009
    高田 礼人
    ウイルス感染症の対策として、ワクチン接種による予防が最も一般的であり効果が期待される。ワクチンは生ワクチンと不活化ワクチンに分類されるが、生ワクチンは安全性の問題、不活化ワクチンは免疫原性の弱さの問題が、それぞれ短所として挙げられ、双方の短所を克服した安全で効果的なワクチンの開発は困難である。特に、生ワクチンは短期間で作出することが不可能であるため、発生頻度が増している新興感染症に対して迅速に対応するためには、不活化ワクチンの効率的な開発および接種法の改良が求められる。本研究では、ウイルス感染に広く認められる抗体依存性感染増強現象(ADE)に着目した。この現象は、ウイルスが抗体を利用してマクロファージや樹状細胞等の抗原提示細胞に効率よく感染するためのメカニズムであると考えられている。本研究では、この抗体の特性を利用して抗原提示細胞に目的の不活化ワクチン抗原を効率よく取り込ませるための手法を開発し、液性免疫および細胞性免疫の両方を誘導する安全なアジュバントとしての抗体の可能性を探る。不活化ウイルス抗原として、ショ糖密度勾配遠心によって精製したエボラウイルスのウイルス様粒子をウイルス表面糖蛋白質に特異的なADE抗体、中和抗体およびどちらの活性も示さないモノクローナル抗体とそれぞれ混合し、マウスの皮下または腹腔内接種して、経時的に血清中の抗体応答を解析し、異なる性質を持つこれらの抗...
    日本学術振興会, 挑戦的萌芽研究, 北海道大学, Principal investigator, Competitive research funding, 20658069
  • Predicting Antigenic Changes of Influenza Viruses by Discovering Patterns of Viral Evolution
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2007 - 2009
    ITO Kimihito; TAKADA Ayato; MINATO Shin-ichi
    Human influenza viruses mutate from time to time, causing annual epidemics worldwide. Given the high mutation rate of the viral gene, it is difficult to select an effective vaccine strain prior to each influenza season. In order to elucidate the pattern of viral evolution, we introduce a bioinformatics technology that analyzes a large number of epidemic strains in a multidimensional space. We found that the relative sequence distances among past epidemic strains could be predicted by a mathematical model. Retrospective tests for 12 years showed that the model could predict the direction of ...
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Coinvestigator not use grants, Competitive research funding, 19300041
  • フィロウイルスの細胞侵入機構と病原性発現に関する研究
    科学研究費助成事業 特定領域研究
    2007 - 2008
    高田 礼人
    フィロウイルスは霊長類に重篤な出血熱を引き起こし、その致死率は90%近くに及ぶこともある。マクロファージや樹状細胞および肝細胞はウイルスの生体内における標的細胞であり、これらの細胞への感染が病原性発現に関与していると考えられている。フィロウイルスの表面糖蛋白質GPはこれらの細胞に発現しているC型レクチンと結合してウイルスの侵入効率を上げることが知られている。本研究では、フィロウイルスのプロトタイプであるマールブルグウイルス(MARV)のC型レクチン介在性細胞侵入機構について、病原性の異なる2つの株を用いて解析を行った。MARVのGPを持つシュードタイプウイルスを、ヒトのガラクトース型C型レクチンhMGLまたは樹状細胞に発現するC型レクチンDC-SIGNを発現させたK562細胞に接種し、フローサイトメーターを用いてGFP陽性のウイルス感染細胞数から各細胞に対する感染価を測定した。霊長類に強い病原性を示すAngola株のGPを持つシュードタイプウイルスは、比較的弱い病原性のMusoke株のGPを持つものよりもレクチン発現細胞への感染性が高いことが判明した。また、547番目のアミノ酸(Angola株 : グリシン、Musoke株 : バリン)がレクチン介在性の細胞侵入効率を決定していることが明らかとなった。MARVの病原性とレクチン発現細胞への感染性との間に相関が見られたことから、...
    日本学術振興会, 特定領域研究, 北海道大学, Principal investigator, Competitive research funding, 19041001
  • 抗体の特異性を利用したターゲティングウイルスの開発
    科学研究費助成事業 萌芽研究
    2007 - 2008
    吉田 玲子; 高田 礼人; 鈴木 定彦
    ウイルス感染症やがんの有効な遺伝子治療法を開発するために、モノクローナル抗体を利用した標的細胞に効率よく目的遺伝子を導入できるターゲティングウイルス(標的指向性ウイルス)の作製を目指した。本研究ではインフルエンザ感染に対するターゲティングウイルスを作製することを目的に、インフルエンザウイルスHAに対するモノクローナル抗体のFab領域を発現するプラスミド、および膜融合タンパク質としてセンダイウイルスFタンパク質を発現するプラスミドを構築した。293T細胞にプラスミドを導入したところ、タンパク質の単独および共発現が確認できた。さらに、抗体と融合タンパク質を細胞に発現させ、G遺伝子をGFPに置換したVSVを感染させて、増殖したウイルスを回収した。作出したウイルス粒子の構造を電子顕微鏡で観察するとともに、抗体とFタンパク質のウイルス粒子内への取り込みを、SDS-PAGEとWestern blotで解析したところ、抗体タンパク質のウイルス粒子への取り込み効率が極めて低いことが判明した。また、ターゲティングウイルスとしての活性も認められなかった。そこで、抗体タンパク質のウイルス取り込み効率を上昇させるために、VSV-Gタンパク質およびFタンパク質が三量体であることから、抗体タンパク質を三量体で発現させることを試みた。抗体遺伝子の3'側にVSV-Gタンパク質またはFタンパク質の細胞外領域4...
    日本学術振興会, 萌芽研究, 北海道大学, Coinvestigator not use grants, Competitive research funding, 19659114
  • A novel therapeutic strategy for zoonotic emerging and reemerging infections
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2005 - 2008
    HORIMOTO Taisuke; GOTOH Hideo; TAKADA Ayato; YASUDA Jiro; SHIMOJIMA Masayuki; TAKADA Ayato; YASUDA Jiro; SHIMOJIMA Masayuki
    人畜共通新興再興感染症は人類の脅威である。特に、H5N1 高病原性鳥インフルエンザの世界的な蔓延とヒトへの感染は、インフルエンザの新たな世界的大流行(パンデミック) を危惧させている。本研究では、こういった世界情勢を鑑み、H5N1 ワクチン開発のための基礎研究を実施した。その結果、不活化ワクチン製造のためのシードウイルスの発育鶏卵ならびにMDCK 細胞における増殖基盤を明らかにし、その知見をもとに高増殖性シードウイルスの作出に成功した。本成果は、今後のインフルエンザワクチン開発におおいに貢献することが期待される。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), The University of Tokyo, Coinvestigator not use grants, Competitive research funding, 17380179
  • すべてのA型インフルエンザに有効な免疫法の開発
    科学研究費助成事業 萌芽研究
    2004 - 2006
    高田 礼人; 堀本 泰介
    インフルエンザウイルスは、表面糖蛋白質ヘマグルチニン(HA)およびノイラミニダーゼ(NA)の抗原性によって様々な亜型に分けられる。現在まで、インフルエンザワクチンは主にウイルスHAに対する血中抗体を誘導することを目的としてきた。しかし、現行の不活化インフルエンザワクチンは抗原性が異なるHA亜型のウイルスには全く効果がない。本研究の目的はこれを克服し、全てのA型インフルエンザに有効な免疫法を検討する事である。これまでに、ホルマリンで不活化したインフルエンザワクチンをマウスの鼻腔内に投与すると、様々な亜型のウイルスに対して交差感染防御が成立することを明らかにした。これにはウイルス表面糖蛋白質に対する亜型特異的中和抗体以外の免疫応答が関与していると考えられた。免疫したマウスのB細胞を用いてハイブリドーマを作出した結果、ウイルス蛋白質に対するIgAおよびIgG抗体を産生するハイブリドーマクローンが多数得られる事が判った。これらの中には様々な亜型のウイルスに交差反応性を示す抗体があった。H1、H2、H3およびH13亜型のHAをもつウイルスに交差反応性を示す中和抗体が得られたため、そのエピトープを同定した結果、このモノクローナル抗体はHAがレセプターに結合する領域の近傍を認識する事が明らかとなった。この領域の構造は亜型に関わらず類似性が高いため、交差反応性を示すことが推測された。これらの...
    日本学術振興会, 萌芽研究, 東京大学->北海道大学, Principal investigator, Competitive research funding, 16658118
  • フィロウイルスの病原性制御に関する研究
    科学研究費助成事業 若手研究(A)
    2004 - 2006
    高田 礼人
    これまでに、エボラウイルスなどの新興感染症は世界の限られた地域でしか認められていないが、昨今の急激な国際化による人の移動および動植物の輸出入に伴い、それらの疾病の原因病原体が他国に拡散する可能性が高まっている。さらに近年、エボラウイルスのような致死率の高い出血熱ウイルスがバイオテロリズムの手段として使用される危険性が高まっており、対策を講じる必要がある。しかし、ウイルス性出血熱に対する効果的な医療手段はほとんどなく、予防・治療法を開発する事が急務となってきた。これまでに申請者は、エボラウイルスZaire株の表面糖蛋白質(GP)分子はウイルスの感染性を中和する抗体および増強する抗体の両方の標的である事を証明した。そこで、エボラウイルスの病原性の強さと感染増強抗体との関わりを調べるために、病原性の非常に強いZaireウイルスと病原性の比較的弱いRestonウイルスの間で、感染増強抗体誘導能を比較した。ZaireウイルスとRestonウイルスGPに対するマウスの抗血清をそれぞれ作成し、血清中の感染増強活性および中和活性を調べたところ、中和活性には殆ど差が無かったのに対して、感染増強活性はZaireウイルスの血清の方が優位に高かった。これは、感染増強抗体が結合できる抗原決定基の種類と数が両ウイルスの間で異なることを示している。また、この感染増強活性は主に血清中のIgG2a抗体によるも...
    日本学術振興会, 若手研究(A), 東京大学->北海道大学, Principal investigator, Competitive research funding, 16689010
  • フィロウイルスの病原性発現とその分子基盤に関する研究
    科学研究費助成事業 特定領域研究
    2004 - 2005
    高田 礼人
    これまでに、エボラウイルスなどの新興感染症は世界の限られた地域でしか認められていないが、昨今の急激な国際化による人の移動および動植物の輸出入に伴い、それらの疾病の原因病原体が他国に拡散する可能性が高まっている。さらに近年、エボラウイルスのような致死率の高い出血熱ウイルスがバイオテロリズムの手段として使用される危険性が高まっており、対策を講じる必要がある。しかし、ウイルス性出血熱に対する効果的な医療手段はほとんどなく、予防・治療法を開発する事が急務となってきた。しかし、エボラウイルスの強い病原性に関わる因子は解明されていない。本ウイルスに対して効果的な予防・治療法を開発するためには、病原性発現のメカニズムを個体、細胞および分子レベルに至るまで明らかにする事が必要である。これまでに申請者は、エボラウイルスZaire株の表面糖蛋白質GP分子はウイルスの感染性を中和する抗体および増強する抗体の両方の標的である事を証明した。そこで、病原性の強いZaireウイルスと病原性の弱いRestonウイルスに対する抗血清を作出し、感染増強活性を比較したところ、補体成分C1qを介した感染増強効果およびFcレセプターを介した感染増強効果のいずれもZaireウイルスに対する抗血清の方が高かった。一方、中和活性に差は認められなかった。以上の成績は、抗体依存性感染増強現象がエボラウイルスの病原性発現に関わっ...
    日本学術振興会, 特定領域研究, 東京大学->北海道大学, Principal investigator, Competitive research funding, 16017228
  • フィロウイルスの病原性発現とその分子基盤に関する研究
    科学研究費助成事業 特定領域研究
    2003 - 2003
    高田 礼人
    エボラウイルスの強い病原性に関わる因子は解明されていない。本ウイルスに対して効果的な予防・治療法を開発するためには、病原性発現のメカニズムを個体、細胞および分子レベルに至るまで明らかにする事が必要である。エボラウイルスZaire株の表面糖蛋白質(GP)に対する抗体の中には、マクロファージ等の細胞で抗体依存性感染増強現象を引き起こすものがある。合成ペプチドおよびキメラGPを用いて、これらの抗体が認識するエピトープの同定を行った結果、少なくとも4箇所の異なるエピトープの存在が明らかになった。マクロファージや未成熟樹状細胞に発現し、galactoseおよびN-acetylgalactosamineに特異的に結合するC-typeレクチン(hMGL)を培養細胞に発現させると、エボラウイルスの感染性が上昇する事を発見した。hMGLはエボラウイルスGP分子上のO-linkの糖鎖を認識している事が示唆された。マクロファージおよび樹状細胞等の抗原提示細胞にエボラウイルスが感染する事によって起こる免疫応答の異常が本ウイルス感染の病原性に深く関わっていると考えられている。本ウイルスはこれらの細胞に効率よく感染するために、抗体、補体あるいはレクチンを利用し、ウイルスレセプターへの吸着効率を上げると考えられる。従って、これらの因子が本ウイルスの病原性発現において重要な役割を演じている事が推察される。マ...
    日本学術振興会, 特定領域研究, 東京大学, Principal investigator, Competitive research funding, 15019023
  • Analysis on cellular factors regulating influenza virus infection using "self-motivating" recombinant virus
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    2002 - 2003
    HORIMOTO Taisuke; GOTO Hideo; TAKADA Ayato
    Progeny viruses are rapidly produced from the cells infected with influenza A viruses for a short period. A several cellular factors regulate virus replication in cells, interacting with viral proteins or RNAs directly or indirectly. In this study, we sought to identify and analyze cellular factors responsible for virus replication. It is hopeful that such information would contribute one to develop novel anti-influenza drugs in the future. To this end, we attempted to establish and use new methodology to identify cellular factors ; that is, "self-motivating" recombinant virus system. In th...
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), The University of Tokyo, Coinvestigator not use grants, Competitive research funding, 14570261
  • Study on development of a live attenuated vaccine for equine influenza infection using reverse genetics
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2001 - 2003
    GOTO Hideo; TAKADA Ayato; HORIMOTO Taisuke; KAWAOKA Yoshihiro; KONDO Takashi
    Equine influenza is an important contagious respiratory disease of horses. In the field of veterinary medicine, equine influenza is recognized as a serious problem because it causes economical loss. Inactivated vaccine for equine influenza has been used to control infection; however its efficacy is not satisfactory.The aim of this study is to develop a live attenuated vaccine for equine influenza infection. A live attenuated vaccine for influenza virus can be generated by insertion of a gene encoding target protein into genome of an attenuated virus. To this end we established a strategy to...
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), The University of Tokyo, Coinvestigator not use grants, Competitive research funding, 13556052
  • フィロウイルスの病原性発現とその分子基盤に関する研究
    科学研究費助成事業 特定領域研究
    2002 - 2002
    高田 礼人
    エボラウイルスの強い病原性に関わる因子は解明されていない。本ウイルスに対して効果的な予防・治療法を開発するためには、病原性発現のメカニズムを個体、細胞および分子レベルに至るまで明らかにする事が必要である。エボラウイルスの表面糖蛋白質(GP)に対して誘導される抗体の中には、ウイルスの感染を増強するものが存在する事をこれまでに明らかにした。感染患者回復期血清を調べると、約半数に感染増強活性が認められたので、実際の感染でも感染増強抗体の産生が誘導されている事が明らかになった。GPに対するモノクローナル抗体(MAb)のうち、ウイルスを中和する活性を示すものに関して、エピトープの同定を行った。VSVのG蛋白質遺伝子をZaire株GP遺伝子に置換したリコンビナントVSVを中和抗体存在下で増殖させてエスケープミュータントを選択し、GPのアミノ酸変異を同定したところ、MAb133/3.16は膜融合ペブチド、MAb226/8.1はレセプター結合領域付近のエピトープを認識すると考えられた。これらの抗体の受動免疫による感染防御効果をマウスモデルを用いて調べた。抗体をウイルス攻撃前あるいは後に腹腔内に投与したマウスは致死量のウイルス感染に対して無症状で耐化した。ウイルス感染後に抗体価の上昇が全く認められなかった事から、ウイルスはマウス体内で殆ど増殖しなかったと考えられる。これらの結果は、中和抗体のみ...
    日本学術振興会, 特定領域研究, 東京大学, Principal investigator, Competitive research funding, 14021018
  • Development of influenza live vaccine by reverse genetics
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2001 - 2002
    KAWAOKA Yoshihiro; HORIMOTO Taisuke; GOTO Hideo; TAKADA Ayato; OSUMI Kunio
    Influenza virus is a highly infectious respiratory pathogen of birds and mammals, including human. It often produces significant mobidity and mortality in humans. Current methods of immunization against influenza virus include parental administration of inactivated influenza virus vaccines, which reduces the incidence of clinical illness in healthy subjects. But in some cases, immunization with inactivated vaccines is associated with very low protection rates or short protection periods.
    Another promising approach to vaccination is the use of live-attenuated influenza viruses. Theses vaccines have shown considerable promise in ongoing clinical trials. However, it has been concerned that the pathogenesis happened to recovered during their replication.
    We propose an alternative approach to the design of live virus vaccines, one that relies on alteration of the influenza A virus M2 protein which is responsible for ion channel activity. It did not show appreciable growth defect in cell culture, although its growth was attenuated in mice. It has shown that this M2 ion channel defective mutant virus protected mice against challenge with lethal doses of influenza virus, indicating the potential or incorporating this M2 alteration in a live influenza vaccine as one of the attenuating mutations.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), The University of Tokyo, 13557023
  • Ecological study of animal influenza viruses : To prepare for the emergence of pandemic influenza
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    2000 - 2002
    KIDA Hiroshi; KATSUNORI Okazaki; YOSHIHIRO Sakoda; YOSHIHIRO Kawaoka; AYATO Takada; TOSHIHIRO Ito
    To provide information on the precursor genes of the next pandemic influenza, epidemiological surveillance of animal and avian influenza viruses was performed. In total, 3,987 fecal samples of migratory waterfowls were collected in Russia, Mongolia, China and Holdcaido, Japan. From these samples, 212 influenza A viruses were isolated H1N2 swine influenza viruses were isolated from pigs with respiratory syndrome in Miyagi Prefecture, Japan. Twenty-five strains of H9N2 viruses were exchanged between 5 centers of global animal influenza network and stated analyzing these viruses.Genetic analys...
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, Coinvestigator not use grants, Competitive research funding, 12375006
  • フィロウイルスの病原性発現機構に関する研究
    科学研究費助成事業 特定領域研究(C)
    2001 - 2001
    高田 礼人
    エボラウイルスの高病原性に関わる因子は解明されていない。本ウイルスに対して効果的な予防・治療法を開発するためには、病原性発現のメカニズムを個体、細胞および分子レベルに至るまで明らかにする事が必要である。本研究では、申請者らが既に確立したVSVシステムおよびウイルスをプラスミドDNAから作出するリバースジェネテイクス法を用いて、病原性に関わる可能性のある蛋白質について変異ウイルスを作出し、ウイルス増殖および病原性発現に関わるウイルス蛋白質の同定を行う。また、マウス実験感染モデルを用いて、エボラウイルスの病原性についてウイルス側のみならず宿主因子をも含めた総合的な解析を行う。GPに対するモノクローナル抗体を作出した。いくつかの抗体は、正常マウス血清存在下でウイルスの感染性を増強した・正常血清の代わりに補体成分C1qを加えると同様の感染増強効果が認められることから、感染増強のメカニズムはGPと抗体の複合物にC1qが結合し標的細胞表面に存在するC1qレセプターを介してウイルスと細胞を架橋し、効率よくウイルスレセプターに結合させる事、あるいはC1qレセプターを介した細胞内シグナルによって細胞の食作用の活性化が起こる事によると考えられた。エボラウイルスのGPは蛋白質分解酵素によって、GP1とGP2に開裂される。ある種のウイルスでは表面糖蛋白質の開裂はウイルスが感染性を獲得するために必要で...
    日本学術振興会, 特定領域研究(C), 東京大学, Principal investigator, Competitive research funding, 13226018
  • 半生インフルエンザウイルスベクターの開発
    科学研究費助成事業 萌芽的研究
    2001 - 2001
    河岡 義裕; 高田 礼人; 五藤 秀男; 堀本 泰介
    申請者らが開発したリバースジェネティクス法を用いて、安全性の高い不活化ワクチンと、侵入門戸の感染防御に有効な弱毒化生ワクチン双方の長所を兼ね備えたワクチン、すなわち細胞に一度だけ感染してウイルス蛋白質を発現し、粘膜免疫および細胞性免疫は誘導するが新たな感染性粒子は産生しない、"半生"ワクチンの開発を試みた。本研究では、インフルエンザウイルスの8本のRNA分節のうち、NS遺伝子に着目した。NS遺伝子がコードするNS2蛋白質を発現しないように変異を導入し、これを用いてNS2欠損ウイルスを作製した。NS2欠損ウイルスを培養細胞に感染させると、主要ウイルス抗原蛋白質であるNP, HA, NA, M1の発現は確認されたが、新たな感染性ウイルス粒子の産生は認められなかった。このウイルスをワクチンとして、3週間おきに3回マウスに経鼻接種して、血中と鼻腔および肺洗浄液中の抗体価を調べたところ、血中からはIgG抗体が、肺洗浄液中からはIgA抗体が検出された。続いて最終免疫から1ヶ月後あるいは3ヶ月後に、致死量の100倍のウイルスでマウスを攻撃した。最終免疫から1ヵ月後に攻撃した場合、対照群のマウスは全て死亡したのに対し、半生ワクチン接種マウスは全て生残した。さらに、最終免疫から3ヵ月後に攻撃した場合でも、半生ワクチン接種マウスは9匹中8匹が生残した。以上の結果は、増殖能を欠く"半生"ワクチンは...
    日本学術振興会, 萌芽的研究, 東京大学, Coinvestigator not use grants, Competitive research funding, 13877044
  • 合成ペプチドを用いた抗ウイルス薬の開発
    科学研究費助成事業 奨励研究(A)
    2000 - 2001
    高田 礼人
    現在までに多くのウイルス感染症は予防、制圧されてきたが、エイズ、ヘルベス、インフルエンザあるいはエボラ出血熱等の感染症に対する効果的な治療法は未だ確立されていない。本研究の目的は特定のアミノ酸配列をもつ合成ベプチドによってウイルスの感染を選択的に阻害する方法を開発する事である。pSKANファージディスプレイシステムを用いて、現在までにインフルエンザウイルス蛋白質に特異的に結合するファージを選択した。また、エボラウイルスの表面糖蛋白をプラスミドから発現させ、精製する事に成功した。これを用いて、この糖蛋白に特異的に結合するファージを選択した。さらに、エボラウイルス糖蛋白の幹部に存在する螺旋状部位が機能的に重要である事が判明したので、その部位と同様のアミノ酸配列を有する合成ペプチドを作成し、エボラウイルス表面糖蛋白でシュードタイプした豚水泡性口炎ウイルスを用いてウイルス感染性中和試験を行った。その結果、約80%のウイルスの侵入が阻止された。この成績は、この合成ペプチドがエボラウイルス表面糖蛋白の立体構造の変化をさまたげ、その侵入を特異的に阻害したためと考えられる。また、エボラウイルスの糖蛋白に対して誘導される抗体の中には、ウイルスの感染性を増強するものがあり、エボラウイルスの強い病原性に関わっている事が示唆された。したがって、この抗体が認識するエピトープを解析し、そのアミノ酸配列を...
    日本学術振興会, 奨励研究(A), 東京大学, Principal investigator, Competitive research funding, 12760192
  • 粘膜免疫応答を誘導するDNAワクチンの開発
    科学研究費助成事業 奨励研究(A)
    1998 - 1999
    高田 礼人
    オーエスキー病ウイルスの表面糖蛋白gBを発現するプラスミドを構築した。これに市販のリポソームとコレラトキシンBサブユニットをアジュバントとして加えたワクチンをマウスに接種し、抗体応答および感染防御効果を調べた。鼻腔内にワクチンを接種したマウスの呼吸器分泌液中にgB特異IgA抗体が血清中にIgG抗体が検出された。これらのマウスの40%が致死量のウイルス攻撃に対して生残した。また、死亡したマウスでも生残時間の延長が認められた。一方、筋肉内にワクチンを接種したマウスでは、血清中にIgG抗体が検出されたが、呼吸器分泌液中には抗体が検出されなかった。これらのマウス全てがウイルス攻撃後、コントロールのマウス同様の経過で死亡した。gB遺伝子を組み込んだリコンビナントバキュロウイルスをマウスの鼻腔内に接種すると同様の抗体応答を誘導することが判明した。これらの成績はgBを動物の粘膜細胞に発現させるワクチンがオーエスキー病の予防に有効である事を示唆している。インフルエンザウイルス(A/Aichi/2/68)のヘマグルチニンを発現するプラスミドを構築した。これを用いてDNAワクチンの粘膜投与における抗CD40抗体または多重膜リボソームのアジュバント効果を検討した。CD40分子は抗原提示細胞の表面糖蛋白であり、これを刺激する事によって免疫応答を増強する事が期待された。抗CD40抗体を混合したワクチン...
    日本学術振興会, 奨励研究(A), 北海道大学, Principal investigator, Competitive research funding, 10760175
  • Molecular mechanisms of infection and pathogenesis of viruses
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A).
    1998 - 1999
    KIDA Hiroshi; ITO Toshihiro; TAKADA Ayato; OKAZAKL Katsunori
    Influenza A viruses of different subtypes were isolated from fecal samples of ducks in their nesting areas in Siberia. Phylogenetic analysis of the NP genes of the isolates in Siberia and those in Hokkaido, Japan on their flyway of migration from Siberia to the south in autumn revealed that they belong to the Eurasian lineage of avian influenza viruses. It is noted that the genes of the isolates in Siberia are closely related to those of H5N1 influenza virus strains isolated from chickens and humans in Hong Kong in 1997 as well as to those of isolates from domestic birds in southern China. ...
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A)., HOKKAIDO UNIVERSITY, Coinvestigator not use grants, Competitive research funding, 10041151
  • G蛋白欠失VSVを用いたウイルス表面糖蛋白の機能解析
    科学研究費助成事業 萌芽的研究
    1998 - 1999
    岡崎 克則; 高田 礼人; 喜田 宏
    ヘルペスウイルス主要糖蛋白の機能を明らかにするためウシヘルペスウイルス1(BHV1)の糖蛋白gBあるいはgCを発現する株化細胞を樹立し、これらにG蛋白遺伝子を欠失した水疱性口炎ウイルス(VSVdelG-G)を感染させて表現型混合ウイルスの回収を試みた。培養上清中に放出されたウイルス粒子をMDBK細胞に接種し、感染性を獲得したか否かをGFPの発現によって調べた。それぞれの糖蛋白を単独で導入した場合あるいはトランスフェクションによってgB、gC、gDの3種を導入した場合にもVSVdelG-Gは感染性を獲得しなかった。したがって、ヘルペスウイルスが宿主細胞に感染する際にはgB、gCおよびgD以外のウイルス蛋白を必要とすることが考えられる。ヘルペスウイルス表面糖蛋白のリセプター特異性を明らかにするため、BHV1gCおよびgBを単独で発現して各種グルコサミノグリカン分子との結合活性を調べた。両糖蛋白はヘパリン、ヘパラン硫酸およびコンドロイチン硫酸Bと結合した。ヘパリン、ヘパラン硫酸およびコンドロイチン硫酸Bはウロン酸としてイヅロン酸を含み、コンドロイチン硫酸AおよびCはグルクロン酸のみを含む。したがって、gCおよびgBは[イヅロン酸-硫酸化アミノ糖]の繰り返し構造を認識するものと考えられる。また、ヘパリンおよびヘパラン硫酸のアミノ糖はグルコサミンであるのに対し、コンドロイチン硫酸群のそ...
    日本学術振興会, 萌芽的研究, 北海道大学, Coinvestigator not use grants, Competitive research funding, 10877051
  • Molecular mechanisms of infection and pathogenesis of viruses
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    1996 - 1998
    KIDA Hiroshi; ITO Toshihiro; UMEMURA Takashi; FUJITA Shoichi; MAEDA Yoshimitsu; NAKAZATO Yoshikazu
    Intravenous injection into chickens with the virus-free extracts from the allantoic membrane of chicken embryos infected with influenza viruses resulted in sudden death due to blood coagulation in the vessels. The chickens injected intravenously with heparin prior to the injection with the extract survived without any signs of disease. The results suggest that some coagulation factors exist in the tissues where virus replicated and that they showed toxiciry to the chickens.To provide information on the pathogenically of fowl plague virus, virological and histopathological comparison was car...
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), HOKKAIDO UNIVERSITY, Coinvestigator not use grants, Competitive research funding, 08406020
  • Studies on the T-cell epitopes of herpesviruses
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    1996 - 1997
    OKAZAKI Katsunori; TAKADA Ayato; KIDA Hiroshi
    An escape mutant of bovine herpesvirus 1 (BHV1) was obtained in the presence of monoclonal antibody against glycoprotein B (gB) , which required complement for virus neutralization. The mutant was also resistant to other 3 monoclonal antibodies against gB,which exhibited complement-independent neutralizing activity. Amino acid substitution of gB of the mutant is now being analyzed. The cytotoxic activity of peripheral blood lymphocytes from BHV1-infected cattle is also being investigated using the mutant-infected primary culture as a target to study whether the amino acid substitution affec...
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), HOKKAIDO UNIVERSITY, Coinvestigator not use grants, Competitive research funding, 08456144
  • Prediction of new pandemic influenza viruses -Distribution of the viruses in waterfowls in their nesting places in Siberia
    Grants-in-Aid for Scientific Research Grant-in-Aid for international Scientific Research
    1995 - 1997
    KIDA Hiroshi; YAMNIKOVA Svetrana; KAWAOKA Yoshihiro; TAKADA Ayato; OKAZAKI Katsunori
    In each summer of 1995-1997,3,000 fecal materials of waterfowls and lake-water samples were collected in Kamchatka, Khabarovsk, and Saha Republic. In 1996, out of 900 fecal samples collected in Kobyaysky area of the basin of the River Lena, 60゚30'N,19 H4N6,1 H4N9,1 H11N1,2 H11N6, and 8 H11N9 influenza viruses were isolated. Although no virus was isolated from the samples collected in "40 islands" area of the River Lena (65゚00'-64゚34'N) , 1 H4N6 and 5 H3N8 viruses were isolated from 120 samples collected in Kobyaysky area and 72 samples in Yakutsk (62゚05'N) , respectively, in 1997. No influe...
    Japan Society for the Promotion of Science, Grant-in-Aid for international Scientific Research, Hokkaido University, Coinvestigator not use grants, Competitive research funding, 07041118
  • エボラウイルスの感染機構の解明
    Competitive research funding
  • ウィルス感染症に対するワクチンの研究
    Competitive research funding
  • Mechanism of Ebola Virus Replication
    Competitive research funding
  • Study on Mucosal Vaccination of Animals against Viral Infections
    Competitive research funding
■ Industrial Property Rights
  • MONOCLONAL ANTIBODIES NEUTRALIZING MARBURG AND RAVN VIRUS
    Patent right, 髙田 礼人; 丸山 隼輝; 齋藤 健; 五十嵐 学
    特願63/575,085(米国仮出願), 05 Apr. 2024
  • 抗ウイルス性ペプチドおよびその応用
    Patent right, 吉田徹彦; 高田礼人; ベイリー小林菜穂子
    特願2017-193292, 03 Oct. 2017
  • ィロウイルスの細胞侵入阻害活性を有するビアリールスルフォンアミド誘導体
    Patent right, 高田礼人; 堺谷政弘; 古山若呼
    特願2017-071729, 31 Mar. 2017
  • 免疫誘導剤
    Patent right, 増田健一; 齊藤隆; 石井保之; 高田礼人; 五十嵐学; 丸山隼輝; 齊藤祐介; 奈良拓也
    特願2016-216753, 11 Nov. 2016
  • エボラウイルスワクチン
    Patent right, 増田健一; 齊藤隆; 石井保之; 高田礼人; 五十嵐学; 丸山隼輝; 齊藤祐介; 奈良拓也
    特願2016-188897, 27 Sep. 2016
  • 全てのエボラウイルス種の感染性を中和するモノクローナル抗体
    Patent right, 高田礼人; 吉田玲子; 古山若呼; 宮本洋子; 丸山隼輝; 飯田茂; 小川進也
    特願2015-161567, 19 Aug. 2015
  • フィロウイルス感染阻害剤のスクリーニング法
    Patent right, 高田礼人; 南保明日香; 黒田誠; 藤倉大輔
    特願2014-210419, 15 Oct. 2014
  • 抗MGL抗体によるフィロウイルス治療薬
    Patent right, 入村 達郎; 河岡 義裕; 高田 礼人; 藤岡 宏樹, 国立大学法人 東京大学
    特願2003-433766, 26 Dec. 2003
    特開2005-187428, 14 Jul. 2005
    200903062567546269
  • ウイルス感染に対する感受性診断のための方法およびキット。
    Patent right, 入村 達郎; 河岡 義裕; 高田 礼人; 藤岡 宏樹, 国立大学法人 東京大学
    特願2003-433767, 26 Dec. 2003
    特開2005-185235, 14 Jul. 2005
    200903072722971678
■ Academic and Social Contribution Activities/Other
Industrial Property Rights
  • International Filovirus Symposium
    2024 - Present
    Planning etc
    Academic society etc
  • PLoS Neglected Tropical Diseases
    2020 - Present
    Planning etc, Peer review
    Peer review etc
  • Scientific Reports
    2019 - Present
    Planning etc, Peer review
    Peer review etc
  • インフルエンザ研究者交流の会
    2018 - Present
    Planning etc
    Academic society etc
  • Viruses
    2018 - Present
    Planning etc, Peer review
    Peer review etc
  • Vector-Borne and Zoonotic Diseases
    2014 - Present
    Planning etc, Peer review
    Peer review etc
  • Archives of Virology
    2011 - Present
    Planning etc, Peer review
    Peer review etc
  • Journal of General Virology
    2015 - 2018
    Planning etc, Peer review
    Peer review etc
  • Influenza Research and Treatment
    2009 - 2017
    Planning etc, Peer review
    Peer review etc
  • Microbiology and Immunology
    2005 - 2007
    Planning etc, Peer review
    Peer review etc
    日本ウイルス学会
  • Science Translational Medicine
    Peer review
    Peer review etc
  • PLoS Pathogens
    Peer review
    Peer review etc
  • Nature Medicine
    Peer review
    Peer review etc
  • Nature Communications
    Peer review
    Peer review etc
  • Lancet Infectious Diseases
    Peer review
    Peer review etc
  • Journal of Virology
    Peer review
    Peer review etc
  • Journal of Infectious Diseases
    Peer review
    Peer review etc
  • Emerging Infectious Diseases
    Peer review
    Peer review etc
  • Cell Reports
    Peer review
    Peer review etc
  • Cell
    Peer review
    Peer review etc
Social Contribution Activities
  • 「ウイルスと向きあう」
    27 Oct. 2024
    Appearance
    TEDxSapporo
    TEDxSapporo 2024
  • エボラウイルスおよびマールブルグウイルス 研究の現状と今後の課題
    29 Jun. 2024
    Lecturer
    Lab. Talk Session 33
  • エボラ出血熱迅速診断キット
    28 Nov. 2023
    Demonstrator
    Africa CDC 他
    CPHIA 2023
  • 新感染症時代を生きる⑤〜アフリカの今…新型コロナと世界の未来は
    24 Apr. 2022
    Appearance, Coverage cooperation, Editor, Informant
    UHB北海道文化放送
    松本裕子の病を知る
  • 新感染症時代を生きる③〜オミクロン株の次は?新型コロナ変異の行方
    10 Apr. 2022
    Appearance, Coverage cooperation, Editor, Informant
    UHB北海道文化放送
    松本裕子の病を知る
  • コロナ下の羅針盤 ウイルスと共生 グローバル化の宿命
    10 Jan. 2022
    Coverage cooperation
    北海道新聞
    北海道新聞
  • 新感染症時代を生きる③〜未知のウイルスと闘う…人獣共通感染症研究所からの警告(後編)
    27 Jun. 2021
    Appearance, Coverage cooperation, Editor, Informant
    UHB北海道文化放送
    松本裕子の病を知る
  • 新感染症時代を生きる②〜未知のウイルスと闘う…人獣共通感染症研究所からの警告
    Jun. 2021
    Appearance, Coverage cooperation, Editor, Informant
    UHB北海道文化放送
    松本裕子の病を知る
  • まなびのひろば ぐんぐん 伸びゆく君へ
    25 May 2021
    Contribution
    北海道新聞
    北海道新聞
  • 「なぜ?」解き明かす探求心を
    25 May 2021
    Coverage cooperation, Informant
    北海道新聞
    まなびのひろば ぐんぐん 伸びゆく君へ
  • 野生のマウンテンゴリラの保護が地球を救う!? 世界の子ども応援SDGs 3時間SP
    05 May 2021
    Coverage cooperation, Advisor, Informant
    TBS
    世界くらべてみたら
  • 「コロナ第4波」拡大のウラで警戒すべき、次に来そうな「人獣共通感染症」の脅威
    30 Apr. 2021
    Coverage cooperation, Advisor, Informant
    講談社
    現代ビジネス
  • 科学者 野口英世
    Jan. 2021
    Coverage cooperation, Advisor, Informant
    NHK
    フランケンシュタインの誘惑 科学史 闇の事件簿
  • パンデミックウイルス インフルエンザと新型コロナ
    14 Oct. 2020
    Lecturer
    朝日新聞
    朝日カルチャーセンター公開講座
  • ウイルスとは何か
    30 Sep. 2020
    Lecturer
    朝日新聞
    朝日カルチャーセンター公開講座
  • ウイルス対策は粘り強さが必要
    24 Aug. 2020
    Coverage cooperation, Informant
    北海道新聞
    北海道新聞
  • 新型コロナウイルスと共存するには 差別、偏見の課題
    19 Aug. 2020
    Coverage cooperation, Informant
    読売新聞
    読売新聞医療健康サイト「ヨミドクター」
  • 日本感染症研究に遅れ 規制・インフラ不足が壁
    16 Aug. 2020
    Coverage cooperation, Informant
    日本経済新聞
    日本経済新聞
  • ウイルスと感染症
    07 Aug. 2020
    Lecturer
    成田ロータリークラブ
    成田ロータリークラブ
  • 感染症と闘う 新型コロナ 夏を乗り切るマスクの工夫
    05 Aug. 2020
    Coverage cooperation, Informant
    毎日新聞
    毎日新聞
  • コロナ撲滅ほぼ不可能
    30 Jul. 2020
    Coverage cooperation, Informant
    北海道新聞
    北海道新聞
  • ウイルスの生態
    29 Jul. 2020
    Lecturer
    北海道新聞
    北海道政経懇話会
  • ウイルスを知る
    22 Jul. 2020
    Lecturer
    北海道新聞
    苫小牧政経文化懇話会
  • 新型コロナウイルスの新しい”宿主”ヒト やがて季節かせのようなウイルスになって定着化か
    15 Jun. 2020
    Coverage cooperation, Informant
    The Big Issue
    The Big Issue
  • 新型コロナ 夏になれば感染減るの?
    10 Jun. 2020
    Coverage cooperation, Informant
    朝日新聞
    朝日新聞
  • 新型コロナのパンデミック 乗り越える鍵は皆が地球規模で考えること
    27 May 2020
    Coverage cooperation, Informant
    聖教新聞
    聖教新聞
  • 聞く語る 野生動物と静かに共生 人類との遭遇増え脅威に
    15 May 2020
    Coverage cooperation, Informant
    北海道新聞
    北海道新聞
  • ウイルスとは何か、その姿に迫る
    13 Apr. 2020
    Lecturer
    TechnionJapan
    丸ノ内 square academy
  • 教えて 新型コロナウイルス
    26 Mar. 2020
    Coverage cooperation, Informant
    十勝毎日新聞
    十勝毎日新聞
  • 聞きたい「新型コロナウイルス」予防の基本は薄める
    03 Mar. 2020
    Coverage cooperation, Informant
    北海道新聞
    北海道新聞
  • ネット情報にデマ
    28 Feb. 2020
    Coverage cooperation, Informant
    北海道新聞
    北海道新聞
  • 動物から人へうつる病気のこと知って
    16 Feb. 2020
    Lecturer, Informant
    朝日小学生新聞
    朝日小学生新聞
  • 謎のウィルス・パニック エボラ出血熱
    Feb. 2020
    Coverage cooperation, Advisor, Informant
    TBS
    ワールド極限ミステリー
  • エボラ治療薬開発への取り組み
    24 Jan. 2020
    Lecturer
    宮崎大学
    宮崎大学 感染症公開セミナー
  • ウイルスは悪者か?
    10 Sep. 2019
    Lecturer
    読売新聞
    サイエンス読書カフェ
  • エボラウイルスを見つける/診断する/治療する
    17 Jun. 2019
    Lecturer
    JICA
    TICAD関連セミナー
  • インハンド
    Jun. 2019
    Advisor, Informant
    TBS
    金曜ドラマ
  • JICAの現場から 日本の医療技術に高評価
    21 Dec. 2018
    Informant
    日刊工業新聞
  • デンカ生研、エボラウイルス迅速診断キット(クイックナビシリーズ)試作品をコンゴ民主共和国へ提供
    28 May 2018
    Others
    日本経済新聞
    日本経済新聞(電子版)
  • 医師10万人アンケートでわかった!
    27 Jan. 2018
    Advisor, Informant
    日本テレビ
    世界一受けたい授業
  • 人獣共通感染症的視点から 鳥インフルエンザとエボラ出血熱を例に
    02 Nov. 2017
    Lecturer
    神津教育研究会
    神津教育研究会「日本の国際協力の現状と成果・課題」
  • 人間が“ゾンビ”になることはあるのか?
    05 Sep. 2017
    Advisor
    NHK
    モーガン・フリーマン 時空を超えて
  • アフリカにおけるウイルス性 人獣共通感染症の調査研究
    28 Aug. 2017
    Lecturer
    SATREPS
    SATREPS 科学と開発をつなぐブリッジ・ワークショップ
  • エボラ出血熱など、人獣共通感染症ウイルスとどう向き合うか
    12 Jul. 2017
    Appearance, Panelist, Lecturer
    文化放送
    ブンナビ薬学特別企画2017
  • デンカ生研と北大、コンゴ民主共和国へエボラウイルス迅速診断キットを提供
    30 May 2017
    Informant
    日本経済新聞
    日本経済新聞(電子版)
  • 人獣共通感染症研究「ウイルス研究の最前線」
    17 Nov. 2016
    Lecturer
    とわの森三愛高等学校
    とわの森三愛高等学校 獣医進学コース 講義
  • エボラ出血熱への挑戦
    24 Oct. 2016
    Appearance, Panelist, Lecturer
    文化放送
    ブンナビ薬学特別企画2016
  • ウイルス研究の最前線 -インフルエンザとエボラ出血熱の話-
    04 Aug. 2016
    Lecturer
    北海道ハイテクノロジー専門学校
    北海道ハイテクノロジー専門学校 平成28年度高校教員バイオ講習会
  • 人獣共通感染症 -インフルエンザとエボラ出血熱の話-
    02 Aug. 2016
    Lecturer
    北海道大学 平成遠友夜学校
  • ウイルスの生態
    04 Jun. 2016
    Lecturer
    北海道大学
    第58回北大祭公開講座
  • エボラ熱の抗体発見 ウイルス全5種抑制
    05 Apr. 2016
    Informant
    北海道新聞
    北海道新聞
  • ウイルスの生態
    19 Mar. 2016
    Panelist, Lecturer
    人間文化研究機構
    人間文化研究機構広領域連携型基幹研究プロジェクト キックオフ・シンポジウム
  • ウイルスって何?-エボラとインフルエンザの話-
    08 Mar. 2016
    Lecturer
    北海道旭川西高等学校
    平成27年度北海道旭川西高等学校「SSH講演会」
  • エボラウイルスの抗体発見 北大チーム
    15 Feb. 2016
    Informant
    読売新聞社
    読売新聞
  • ウイルスはどうやって生き残っているのか
    18 Nov. 2015
    Lecturer
    慶應学術事業会
    慶應丸の内シティキャンパス定例講演会『夕学五十講』
  • エボラウイルス
    13 Nov. 2015
    Lecturer
    宮崎大学
    宮崎大学 第5回国際シンポジウム
  • 人獣共通感染症の研究最前線 ~エボラ出血熱とインフルエンザ~
    18 Oct. 2015
    Lecturer
    サイエンステクノフロンティアフォーラム
    第91回サイテックサロン
  • 人獣共通感染症って?-エボラ出血熱とインフルエンザの話-
    29 Sep. 2015
    Lecturer
    札幌啓成高等学校
    平成27年度スーパー・サイエンス・ハイスクール特別科学講演会
  • 協和発酵キリン 北大とエボラ抗体薬開発 ウイルス全種に効果期待
    16 Sep. 2015
    Informant
    化学工業日報社
    化学工業日報
  • Recent Advance in Ebolavirus Research: Epidemiology & Virology
    12 Aug. 2015
    Lecturer
    Airlangga University
    AIRC International Seminar: Bioterrorism and Agroterrorism in Indonesia
  • エボラウイルス ー研究の現状と展望ー
    05 Aug. 2015
    Lecturer
    日本学術会議第二部(生命科学分野)部会
    公開学術講演会
  • エボラ出血熱への挑戦
    28 Jul. 2015
    Appearance
    文化放送キャリアパートナーズ 帝京大学
    ブンナビ薬学特別企画2015
  • エボラウイルス研究の最前線
    20 Jul. 2015
    Panelist, Lecturer
    北海道大学
    平成27年度北海道大学公開講座
  • エボラ感染 15分で判定 北大教授ら キット開発、実用化へ
    01 Apr. 2015
    Informant
    北海道新聞
    北海道新聞
  • エボラ感染 15分で検査 北大教授ら キット開発
    01 Apr. 2015
    Informant
    読売新聞
    読売新聞
  • エボラ出血熱:現状と研究の最前線
    02 Mar. 2015
    Lecturer
    岐阜大学
    岐阜大学市民講座
  • エボラウイルスに迫る
    24 Feb. 2015
    Panelist, Lecturer
    北海道大学
    北海道大学 創成研究機構第 12 回 創成シンポジウム 感染症研究の最前線 ― エボラ・結核を例に―
  • エボラおよびマールブルグウイルスによる感染症
    15 Jan. 2015
    Panelist
    厚生労働省
    平成26年度新型インフルエンザ等新興・再興感染症研究推進事業シンポジウム
  • エボラ出血熱とBSL-4
    21 Sep. 2014
    Lecturer
    長崎大学熱帯医学研究所
    長崎大学熱帯医学研究所 「市民公開特別講座」
  • 北海道大学ザンビア拠点での取り組み
    23 Aug. 2014
    Panelist
    J-GRID
    J-GRID市民公開講演会「いま話題の感染症-SFTS、MERS、エボラ出血熱」
  • 鳥インフルエンザ
    18 Dec. 2013
    Lecturer
    石狩家畜保健衛生所
    平成25年度家畜保健衛生所病性鑑定技術検討会
  • 「エボラ出血熱ウイルス」…糸のような形の、やさしそうで怖いウイルスの話
    13 Jun. 2013
    Lecturer
    日本ウイルス学会
    みちのくウイルス塾
  • 海外のBSL4 施設での実験の状況
    14 Nov. 2012
    Lecturer
    日本学術会議
    日本学術会議 公開シンポジウム
  • 人獣共通感染症としてのインフルエンザ
    09 Nov. 2012
    Lecturer
    北海道青少年科学文化財団
    第21回先端科学移動大学2012
  • H5N1高病原性鳥インフルエンザウイルスと私との関わり
    27 Oct. 2012
    Lecturer
    宮崎大学
    第2回宮崎大学 鳥インフルエンザシンポジウム
  • 人獣共通感染症としてのインフルエンザ
    13 Nov. 2010
    Lecturer
    北海道青少年科学文化財団
    第19回先端科学移動大学2010
  • 人獣共通感染症としてのインフルエンザ
    16 Sep. 2009
    Lecturer
    IUMS
    市民公開講座 微生物をよく知ろう
  • インフルエンザウイルスの病原性と宿主域
    22 Jan. 2008
    Lecturer
    自衛隊
    自衛隊北部防衛衛生学会
  • エボラウイルスの感染、免疫、疫学
    22 Jul. 2006
    Lecturer
    宮崎大学
    人獣共通感染症 教育公開フォーラム
  • Ayato Takada and the Ebola Virus
    Others
    三修社
    英語教科書
Media Coverage
  • 人獣共通感染症、エボラ迅速診断キット
    01 Aug. 2024
    MUVI TV Zambia
    Main News
  • マールブルグ病
    22 Aug. 2023
    ラジオNIKKEI第一放送
    NIKKEIドクターサロン
    [Media report]
  • 報道ランナー
    26 Jul. 2022
    関西テレビ
    報道ランナー
  • エボラ10分で判定 北大など開発診断キット 国内製造販売承認 感染地域普及目指す
    07 Apr. 2021
    北海道新聞
    [Paper]
  • デンカと北大、エボラウイルス抗原迅速診断キットの国内製造販売承認を取得
    23 Mar. 2021
    日本経済新聞
    [Paper]
  • 世界の果てまでも追い続ける 「ウイルスハンター」と呼ばれる2人の日本人研究者
    16 Sep. 2020
    朝日新聞
    朝日新聞GLOBE+
    [Internet]
  • 「鳥インフルエンザ 新たな脅威」
    04 Nov. 2019
    NHK
    サイエンスZERO
    [Media report]
  • エボラ熱、日本勢も対策 コンゴで感染拡大 北海道大学検査キット試作 アンジェス新薬の開発進む
    12 Aug. 2019
    日本経済新聞
    日本経済新聞
    [Paper]
  • エボラ出血熱の治療薬開発を目指して 人類史上、最も危険なウイルスに挑む
    01 Aug. 2019
    DIAMONDハーバード・ビジネス・レビュー
    [Paper]
  • 死に至る病「エボラ」から世界を救う…日本人ウイルス学者の奮闘記
    15 Jan. 2019
    現代ビジネス
    [Internet]
  • ウイルスは悪者か
    09 Dec. 2018
    NHK
    「マイあさラジオ」
    [Media report]
  • 「風疹、インフルエンザ、HIV、エボラ出血熱~ウイルス学者・高田礼人さんが語る~ウイルスとはいったい何なのか?」
    28 Nov. 2018
    TBS
    Session22
    [Media report]
  • The Battle Against Ebola
    02 Jul. 2018
    NHK
    Direct Talk
    [Internet]
  • Speedy Ebola tests help contain Africa's latest outbreak
    11 Jun. 2018
    Nature
    Nature
    [Paper]
  • 「伊集院光とらじおと」
    04 Jun. 2018
    TBS
    「伊集院光とらじおと」 TBS
    [Media report]
  • A型インフルエンザウイルス—ウイルス学の視点から
    2018
    メディカルノート
    メディカルノート
    [Internet]
  • 加計学園問題と獣医師の現状
    10 Jun. 2017
    TBS
    報道特集
    [Media report]
  • スクラムトーク 日本はもっと人道で貢献できる ウイルスとの戦いに「世界市民」への道 哲学ある人材を大学から輩出したい
    20 Mar. 2016
    聖教新聞社
    聖教新聞
    [Paper]
  • 『緊急!池上彰と考える 今年の細菌・ウイルス大疑問』
    27 Jan. 2016
    TBS
    テレビ未来遺産
    [Media report]
  • エボラ出血熱への挑戦
    25 Oct. 2015
    文化放送キャリアパートナーズ 高崎健康福祉大学
    ブンナビ薬学特別企画2015
    [Pr]
  • Ebola spurs creation of Japan's first maximum-security biolab
    13 Aug. 2015
    Nature
    Nature
    [Paper]
  • エボラ出血熱 適切な対応で感染は防げる
    01 May 2015
    民医連
    民医連 いつでも元気
    [Paper]
  • エボラウイルス解明に挑戦
    01 May 2015
    北海道建設新聞
    真砂徳子の起ーパーソン ~風をおこす人々~
    [Paper]
  • 未踏の世界へ エボラに効く抗体を追う
    30 Apr. 2015
    毎日新聞社
    毎日新聞
    [Paper]
  • Ebola Antibodies in Zambia Bats Match West African Virus
    27 Mar. 2015
    Bloomberg News
    [Internet]
  • ウイルスの専門家に聞く感染症とエボラウイルスの真実
    13 Mar. 2015
    洋泉社
    感染症クライシス
    [Others]
  • 日曜Navi ほっかいどう知究人 エボラ出血熱解明に挑む
    08 Mar. 2015
    北海道新聞
    北海道新聞
  • ウイルスと感染症
    10 Feb. 2015
    株式会社 ニュートンプレス
    Newton 別冊
    [Paper]
  • エボラ出血熱、高病原性鳥インフルエンザ……人獣共通感染症を研究 エボラウイルスの抗体もーー高田礼人さんの挑戦
    01 Feb. 2015
    株式会社ビッグイシュー日本版
    ビッグイシュー日本版
    [Paper]
  • ウイルス
    31 Jan. 2015
    日本テレビ
    世界一受けたい授業
    [Media report]
  • 脅威のエボラ、英知をかけて挑む ウイルス学者・高田礼人
    05 Jan. 2015
    NHK
    NHK プロフェッショナル~仕事の流儀
    [Media report]
  • 挑む Front Runner アフリカの森林でエボラウイルスを追う
    01 Jan. 2015
    日経サイエンス社
    日経サイエンス
    [Paper]
  • エボラ…日本の課題
    29 Nov. 2014
    報道特集
    [Media report]
  • The Ebola Questions
    30 Oct. 2014
    Nature
    Nature
    [Paper]
  • 猛威を振るう出血熱ウイルス 感染ルートや生態は未解明 野生動物に寄生、撲滅困難
    01 Sep. 2014
    産経新聞
    産経新聞
    [Paper]
  • 北大、エボラ熱阻止支援 ザンビア 感染の疑い診断
    17 Aug. 2014
    北海道新聞
    北海道新聞
    [Paper]
  • エボラ早期診断 北大が一役
    14 Aug. 2014
    朝日新聞
    朝日新聞
    [Paper]
  • ウイルス学魂
    22 Dec. 2013
    BS日テレ
    加藤浩次の本気対談!『コージ魂!!』
    [Media report]
  • Orang-utans infected by mystery Ebola-like virus
    06 Nov. 2012
    New Scientist
    [Internet]
  • 獣医師たちのたたかい こうもりからウイルスを探す
    15 Jan. 2012
    朝日新聞
    朝日新聞グローブ
    [Paper]
  • ウィルス学者・高田礼人
    28 Feb. 2010
    毎日放送
    情熱大陸
    [Media report]
  • インフルエンザ21世紀
    20 Dec. 2009
    文春新書
    インフルエンザ21世紀
    [Others]
  • 新型インフルエンザ 専門家が予想…脅威の感染力
    16 Dec. 2008
    日本テレビ
    スッキリ
    [Media report]
  • ウイルス その奇妙な生き方〜ウイルス学 高田礼人〜
    12 Jun. 2008
    NHK
    爆笑問題のニッポンの教養
    [Media report]
  • シリーズ ミクロの生命体1 新型インフルエンザを阻止せよ!
    06 Nov. 2005
    テレビ朝日
    素敵な宇宙船地球号
    [Media report]