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Kariwa Hiroaki

Faculty of Veterinary Medicine Veterinary Medicine Preventive Veterinary MedicineSpecially Appointed Professor
International Institute for Zoonosis ControlSpecially Appointed Professor

Researcher basic information

■ Degree
  • Ph.D, Hokkaido University
■ URL
researchmap URLホームページURL■ Various IDs
J-Global ID■ Research Keywords and Fields
Research Keyword
  • 人獣共通感染症
  • ウイルス学
  • 公衆衛生学
  • Zoonosis
  • Virology
  • Public Health
Research Field
  • Life Science, Veterinary medical science
■ Educational Organization

Career

■ Career
Position History
  • 大学院国際感染症学院副学院長, 2021年4月1日 - 2023年3月31日
  • 大学院国際感染症学院副学院長, 2023年4月1日 - 2025年3月31日

Research activity information

■ Awards
  • Apr. 2007, The Japanese Society of Veterinary Science, The Award of the Japanese Society of Veterinary Science
    Comparative epidemiological study of hantavirus infection among wild rodents
    KARIWA Hiroaki
■ Papers
  • Development of blood-brain barrier-penetrating antibodies for neutralizing tick-borne encephalitis virus in the brain.
    Mizuki Fukuta; Sayo Fukano; Naoya Maekawa; Shintaro Kobayashi; Shunsuke Okamoto; Minato Hirano; Junko Nio-Kobayashi; Hiroaki Kariwa; Shigeru Kawakami; Satoru Konnai; Kentaro Yoshii
    mSphere, 10, 7, e0018425, 29 Jul. 2025, [International Magazine]
    English, Scientific journal, UNLABELLED: Tick-borne encephalitis virus (TBEV) belongs to the genus Flavivirus and causes tick-borne encephalitis (TBE), a disease characterized by severe neurological symptoms with a high mortality rate. Currently, no specific antiviral treatments have been developed for TBE. The blood-brain barrier (BBB) restricts drug delivery to the central nervous system, posing a major challenge in developing effective therapies targeting TBEV in the brain. In this study, we developed recombinant anti-TBEV antibodies fused with BBB-penetrating rabies virus glycoprotein (RVG) peptides to facilitate their transport across the BBB. The fusion of RVG peptides to the C-terminus of the heavy chain of whole antibodies or single-chain variable fragment had minimal impact on their neutralizing ability against TBEV. The RVG fusion enhanced antibody binding to the surface of a human brain endothelial cell line and increased permeability in an in vitro BBB model. The RVG-fused antibodies exhibited a higher transport efficiency to the brain than the non-fused antibodies following peripheral injection in mice. Notably, the peripheral administration of the RVG-fused whole antibody after viral invasion into the brain significantly neutralized TBEV in the brains of infected mice. These findings suggest that RVG-fused antibodies represent a promising therapeutic strategy for treating TBE once the virus has entered the brain. IMPORTANCE: Tick-borne encephalitis virus is a neuroinvasive pathogen that causes severe neurologic disease, significantly affecting patients' quality of life. No specific antiviral treatment is available for tick-borne encephalitis caused by virus multiplication in the brain. The delivery of drugs to the brain via peripheral administration is often obstructed by the blood-brain barrier. To develop targeted antiviral therapies for brain infections, we engineered recombinant antibodies capable of crossing the blood-brain barrier via brain-targeted ligands. These antibodies exhibited permeability across the blood-brain barrier in both in vitro and in vivo models and notably effectively neutralized the virus within the brain following peripheral administration. This study is the first to highlight the therapeutic potential of brain-targeted recombinant antibodies after viral entry into the brain, offering a promising pathway for the development of effective antiviral treatments for tick-borne encephalitis.
  • Molecular evolution of Hokkaido virus, a genotype of Orthohantavirus puumalaense, among Myodes rodents.
    Duong Thi Ngoc Thuy; Michihito Sasaki; Yasuko Orba; Passawat Thammahakin; Keisuke Maezono; Shintaro Kobayashi; Hiroaki Kariwa
    Virology, 597, 110168, 110168, 03 Jul. 2024, [International Magazine]
    English, Scientific journal, Viruses in the genus Orthohantavirus within the family Hantaviridae cause human hantavirus infections and represent a threat to public health. Hokkaido virus (HOKV), a genotype of Orthohantavirus puumalaense (Puumala virus; PUUV), was first identified in Tobetsu, Hokkaido, Japan. Although it is genetically related to the prototype of PUUV, the evolutionary pathway of HOKV is unclear. We conducted a field survey in a forest in Tobetsu in 2022 and captured 44 rodents. Complete coding genome sequences of HOKVs were obtained from five viral-RNA-positive rodents (four Myodes rufocanus bedfordiae and one Apodemus speciosus). Phylogenetic analysis revealed a close relationship between the phylogenies and geographical origins of M. rufocanus-related orthohantaviruses. Comparison of the phylogenetic trees of the S segments of orthohantaviruses and the cytochrome b genes of Myodes species suggested that Myodes-related orthohantaviruses evolved in Myodes rodent species as a result of genetic isolation and host switching.
  • Rab27a promotes degradation of West Nile virus E protein in the lysosome.
    Shintaro Kobayashi; Seira Kawai; Yukine Fukuda; Haruto Eguchi; Keisuke Maezono; Passawat Thammahakin; Hirofumi Sawa; Hiroaki Kariwa
    iScience, 27, 4, 109539, 109539, 19 Apr. 2024, [International Magazine]
    English, Scientific journal, Rab27a, a Rab family small GTPases, plays an important role in the trafficking and secretion of the intracellular proteins and has been reported to promote various viral multiplication. However, whether Rab27a is involved in West Nile virus (WNV) multiplication is unknown. This study examined the ability of Rab27a to suppress WNV multiplication. The inhibition of Rab27a expression increased viral multiplication and the intracellular levels of WNV structural proteins, E and prM proteins. Rab27a partially colocalized with E protein, mainly in the perinuclear region, while inhibition of Rab27a expression resulted in diffuse subcellular localization of E protein. In addition, some of the perinuclear E protein colocalized with the lysosomal marker LAMP1, and inhibition of lysosomal acidification increased intracellular levels of Rab27a and E proteins. These observations suggested that Rab27a inhibits WNV multiplication by inducing the degradation of viral protein in lysosomes.
  • Ubiquitin accumulation induced by the finger and palm sub-domains of NS5 modulates the replication of West Nile virus.
    Shintaro Kobayashi; Ryoko Kawakami; Chisaki Takeda; Keisuke Maezono; Passawat Thammahakin; Haruto Eguchi; Bernard M Hang'ombe; Yasuko Orba; Hirofumi Sawa; Kentaro Yoshii; Hiroaki Kariwa
    Virology, 588, 109902, 109902, Nov. 2023, [International Magazine]
    English, Scientific journal, West Nile virus (WNV) causes encephalitis in human and animals. WNV is phylogenetically classified into at least five distinct genetic lineages with different pathogenicity. The pathogenesis of West Nile encephalitis is affected by ubiquitin accumulation in infected cells, but the mechanism is unknown. In this study, the association between ubiquitin accumulation and WNV pathogenicity was investigated. Ubiquitin accumulation was detected in cells infected with NY99 strain belonging to lineage-1, but not FCG and Zmq16 strains belonging to lineage-2. Substitution of the Finger and Palm sub-domains of NS5 from lineage-1 to -2 decreased ubiquitin accumulation and viral replication. Furthermore, the survival rate was increased, and viral replication and ubiquitin accumulation in the brain were attenuated, in mice inoculated with the substituted WNV compared with lineage-1 WNV. Therefore, the intracellular ubiquitin accumulation induced by the Finger and Palm sub-domains of NS5 is linked to the differences in pathogenicity among WNV lineages.
  • ウエストナイルウイルス感染で形成される複製複合体内に局在する二本鎖RNAを標的とした抗ウイルス効果の検討
    江口 悠人; 前園 佳祐; Thammahakin Passawat; 石橋 和大; 好井 健太朗; 苅和 宏明; 小林 進太郎
    日本獣医学会学術集会講演要旨集, 166回, 151, 151, (公社)日本獣医学会, Sep. 2023
    Japanese
  • 核膜孔複合体の機能障害に着目したウエストナイルウイルス感染による宿主タンパク質の核-細胞質間輸送の障害と病態形成との関連の解明
    前園 佳祐; Thammahakin Passawat; 好井 健太朗; 苅和 宏明; 小林 進太郎
    日本獣医学会学術集会講演要旨集, 166回, 151, 151, (公社)日本獣医学会, Sep. 2023
    Japanese
  • ウエストナイルウイルスの脳内侵入機構解明のための脳組織の病理組織学的解析
    梶山 実紗; 福田 幸音; 佐々木 道仁; Passawat Thammahkin; 前園 佳祐; 長谷部 理絵; 村上 正晃; 苅和 宏明; 小林 進太郎
    日本獣医学会学術集会講演要旨集, 166回, 150, 150, (公社)日本獣医学会, Sep. 2023
    Japanese
  • ダニ媒介脳炎における検査法の評価および後方視的調査結果について
    山口 宏樹; 駒込 理佳; 三好 正浩; 伊東 拓也; 後藤 明子; 三津橋 和也; 渡 慧; 山野 公明; 小林 進太郎; 苅和 宏明; 好井 健太朗
    病原微生物検出情報月報, 44, 8, 128, 130, 国立感染症研究所, Aug. 2023
    Japanese, 2017年6月~2023年3月までのダニ媒介脳炎の検査結果を示し、その検査法の有用性について検討した。さらに、2017年6月以前のダニ媒介感染症疑い症例における後方視的調査結果を報告した。当所に搬入された294症例369検体についてELISAおよび中和試験を実施した。その結果、新たに3症例(6検体)からダニ媒介脳炎ウイルス(TBEV)に対する特異的抗体が検出された。ELISAと中和試験の結果を比較した結果、IgM捕捉ELISAにおいて陽性の6検体では偽陰性・偽陽性はみられず、IgG-ELISAで陰性、中和試験において抗体が検出された3検体はそれぞれの回復期血清においてIgG抗体陽転が確認された。2017年6月以前に当所に搬入された88症例99検体において後方視的調査を実施した。その結果、3症例(3検体)からIgM抗体および中和抗体が検出され、新たに2名のTBEV抗体陽性症例の存在が明らかとなった。
  • Detection of disease-associated microglia among various microglia phenotypes induced by West Nile virus infection in mice.
    Passawat Thammahakin; Keisuke Maezono; Naoya Maekawa; Hiroaki Kariwa; Shintaro Kobayashi
    Journal of neurovirology, 29, 4, 367, 375, Aug. 2023, [International Magazine]
    English, Scientific journal, West Nile virus (WNV) has emerged as a significant cause of viral encephalitis in humans and horses. However, the pathogenesis of the West Nile encephalitis remains unclear. Microglia are activated by WNV infection, and the pathogenic involvement of their phenotypes is controversial. In this study, we examined the diversity of microglia phenotypes caused by WNV infection by assessing various microglia markers and identified disease-associated microglia in WNV-infected mouse brain tissue. Cells positive for general microglia markers such as Iba1, P2RY12, or TMEM119 were detected in the control and WNV-infected brain tissue. The morphology of the positive cells in brain tissue infected by WNV was different from that of control brain tissue, indicating that WNV infection induced activation of microglia. The activated microglia were classified into various phenotypes by investigation of specific marker expression. Among the activated microglia, disease-associated microglia that were positive for CD11c and weakly positive for TMEM119 were detected close to the WNV-infected cells. These results indicate that WNV infection induces activation of diverse microglia phenotypes and that disease-associated microglia may be associated with the pathogenicity of WNV infection in the mouse brain.
  • Development of recombinant West Nile virus expressing mCherry reporter protein.
    Shintaro Kobayashi; Yukine Fukuda; Kentaro Yoshii; Passawat Thammahakin; Keisuke Maezono; Luděk Eyer; Daniel Růžek; Hiroaki Kariwa
    Journal of virological methods, 317, 114744, 114744, Jul. 2023, [International Magazine]
    English, Scientific journal, West Nile virus (WNV) is transmitted to humans and animals by a mosquito and enters the central nervous system, leading to lethal encephalitis. Reporter viruses expressing fluorescent proteins enable detection of infected cells in vitro and in vivo, facilitating evaluation of the dynamics of viral infection, and the development of diagnostic or therapeutic methods. In this study, we developed a method for production of a recombinant replication-competent WNV expressing mCherry fluorescent protein. The expression of mCherry was observed in viral antigen-positive cells in vitro and in vivo, but the growth of the reporter WNV was reduced as compared to the parental WNV. The expression of mCherry was stable during 5 passages in reporter WNV-infected culture cells. Neurological symptoms were observed in mice inoculated intracranially with the reporter WNV. The reporter WNV expressing mCherry will facilitate research into WNV replication in mouse brains.
  • Necroptosis of neuronal cells is related to the neuropathology of tick-borne encephalitis.
    Dai Tsujino; Kentaro Yoshii; Misa Kajiyama; Yuji Takahashi; Naoya Maekawa; Hiroaki Kariwa; Shintaro Kobayashi
    Virus research, 321, 198914, 198914, 03 Sep. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Tick-borne encephalitis virus (TBEV) is a zoonotic virus that causes tick-borne encephalitis (TBE) in humans. Infections of Sapporo-17-Io1 (Sapporo) and Oshima 5-10 (Oshima) TBEV strains showed different pathogenic effects in mice. However, the differences between the two strains are unknown. In this study, we examined neuronal degeneration and death, and activation of glial cells in mice inoculated with each strain to investigate the pathogenesis of TBE. Viral growth was similar between Sapporo and Oshima, but neuronal degeneration and death, and activation of glial cells, was more prominent with Oshima. In human neuroblastoma cells, apoptosis and pyroptosis were not observed after TBEV infection. However, the expression of the necroptosis marker, mixed lineage kinase domain-like (MLKL) protein, was upregulated by TBEV infection, and this upregulation was more pronounced in Oshima than Sapporo infections. As necroptosis is a pro-inflammatory type of cell death, differences in necroptosis induction might be involved in the differences in neuropathogenicity of TBE.
  • ダニ媒介性脳炎の治療法開発に向けた血液脳関門透過性分子の研究
    福田 美津紀; 深野 紗代; 小林 進太郎; 前川 直也; 高橋 侑嗣; 平野 港; 苅和 宏明; 今内 覚; 好井 健太朗
    日本獣医学会学術集会講演要旨集, 165回, [F1P, 12], (公社)日本獣医学会, Sep. 2022
    Japanese
  • ダニ媒介性脳炎の治療法開発に向けた血液脳関門透過性分子の研究
    福田 美津紀; 深野 紗代; 小林 進太郎; 前川 直也; 高橋 侑嗣; 平野 港; 苅和 宏明; 今内 覚; 好井 健太朗
    日本獣医学会学術集会講演要旨集, 165回, [F1P, 12], (公社)日本獣医学会, Sep. 2022
    Japanese
  • Analysis of the relationship between replication of the Hokkaido genotype of Puumala orthohantavirus and autophagy.
    Kazuma Tamiya; Shintaro Kobayashi; Kentaro Yoshii; Hiroaki Kariwa
    Virus research, 318, 198830, 198830, 28 May 2022, [Peer-reviewed], [Last author], [International Magazine]
    English, Scientific journal, Hantaviruses are potentially fatal zoonotic pathogens of the family Hantaviridae. No human infection by the Hokkaido genotype of Puumala orthohantavirus (PUUV-Hok) has been reported. However, other PUUV genotypes cause hemorrhagic fever with renal syndrome (HFRS) in humans. Autophagy is a highly conserved lysosomal degradation process in eukaryotic cells that affects the replication of various viruses. In this study, we examined the role of autophagy in PUUV-Hok replication. PUUV-Hok infection induced the expression of LC3-II, an autophagosome marker, and the nucleocapsid protein (NP) of PUUV-Hok was colocalized with punctate structures of LC3. Inhibition of autophagy using an siRNA for Atg5, an autophagy-related gene, increased the replication of PUUV-Hok, whereas an autophagy inducer decreased its replication. Inhibition of lysosomal degradation increased the expression of NP and LC3-II. In summary, autophagy was induced by PUUV-Hok infection, which inhibited PUUV-Hok replication in a manner related to the degradation of the NP in lysosomes.
  • Y-shaped RNA secondary structure of a noncoding region in the genomic RNA of tick-borne encephalitis virus affects pathogenicity.
    Shoko Nishiyama; Minato Hirano; Memi Muto; Mao Kambara; Naoto Ito; Shintaro Kobayashi; Hiroaki Kariwa; Kentaro Yoshii
    Microbiology and immunology, 66, 5, 234, 237, May 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Tick-borne encephalitis virus (TBEV) is a zoonotic virus that causes encephalitis in humans. Various deletions have been reported in a variable region of the 3' untranslated region of the TBEV genome. This study analyzed the role of a Y-shaped secondary structure in the pathogenicity of TBEV by using reverse genetics. Deletion of the structure increased the mortality rate of virus-infected mice but did not affect the virus multiplication in cultured cells and organs. The results indicate that the secondary structure is involved in the regulation of TBEV pathogenesis.
  • Characterization of tick-borne encephalitis virus isolated from tick infesting dog in central Hokkaido in 2018.
    Yuji Takahashi; Shintaro Kobayashi; Ryo Nakao; Hiroaki Kariwa; Kentaro Yoshii
    Ticks and tick-borne diseases, 13, 2, 101900, 101900, Mar. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Tick-borne encephalitis virus (TBEV) is a zoonotic virus belonging to the genus Flavivirus of the family Flaviviridae, causing meningitis or meningoencephalitis in humans. TBEV is widely distributed across the Eurasian northern regions, including Japan. Dogs have been reported to be sentinel hosts of TBEV in endemic areas, but studies of ticks infesting dogs are limited in Japan. This study isolated a novel TBEV strain from a tick (Ixodes ovatus) collected on a dog from central Hokkaido. Whole-genome sequencing revealed that the isolated strain belonged to the Far Eastern subtype of TBEV and was classified under a different subcluster of other Japanese isolates. Nanporo-18-44 showed growth properties similar to those of Oshima 5-10 both in vitro and in vivo. The pathogenicity of both viruses was similar in mice infected intracerebrally, however they showed a distinct distribution in the infected neurons of the mouse brain. Our results suggest that infections of humans and animals by unknown strains of TBEV exist in other areas of Japan. Further surveys including those conducted outside of Hokkaido, are required to elucidate the epidemiological risk of TBEV in Japan.
  • 5-Hydroxymethyltubercidin exhibits potent antiviral activity against flaviviruses and coronaviruses, including SARS-CoV-2.
    Kentaro Uemura; Haruaki Nobori; Akihiko Sato; Takao Sanaki; Shinsuke Toba; Michihito Sasaki; Akiho Murai; Noriko Saito-Tarashima; Noriaki Minakawa; Yasuko Orba; Hiroaki Kariwa; William W Hall; Hirofumi Sawa; Akira Matsuda; Katsumi Maenaka
    iScience, 24, 10, 103120, 103120, 22 Oct. 2021, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal, Newly emerging or re-emerging viral infections continue to cause significant morbidity and mortality every year worldwide, resulting in serious effects on both health and the global economy. Despite significant drug discovery research against dengue viruses (DENVs) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), no fully effective and specific drugs directed against these viruses have been discovered. Here, we examined the anti-DENV activity of tubercidin derivatives from a compound library from Hokkaido University and demonstrated that 5-hydroxymethyltubercidin (HMTU, HUP1108) possessed both potent anti-flavivirus and anti-coronavirus activities at submicromolar levels without significant cytotoxicity. Furthermore, HMTU inhibited viral RNA replication and specifically inhibited replication at the late stages of the SARS-CoV-2 infection process. Finally, we demonstrated that HMTU 5'-triphosphate inhibited RNA extension catalyzed by the viral RNA-dependent RNA polymerase. Our findings suggest that HMTU has the potential of serving as a lead compound for the development of a broad spectrum of antiviral agents, including SARS-CoV-2.
  • A novel nairovirus associated with acute febrile illness in Hokkaido, Japan.
    Fumihiro Kodama; Hiroki Yamaguchi; Eunsil Park; Kango Tatemoto; Mariko Sashika; Ryo Nakao; Yurino Terauchi; Keita Mizuma; Yasuko Orba; Hiroaki Kariwa; Katsuro Hagiwara; Katsunori Okazaki; Akiko Goto; Rika Komagome; Masahiro Miyoshi; Takuya Ito; Kimiaki Yamano; Kentaro Yoshii; Chiaki Funaki; Mariko Ishizuka; Asako Shigeno; Yukari Itakura; Lesley Bell-Sakyi; Shunji Edagawa; Atsushi Nagasaka; Yoshihiro Sakoda; Hirofumi Sawa; Ken Maeda; Masayuki Saijo; Keita Matsuno
    Nature communications, 12, 1, 5539, 5539, 20 Sep. 2021, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal, The increasing burden of tick-borne orthonairovirus infections, such as Crimean-Congo hemorrhagic fever, is becoming a global concern for public health. In the present study, we identify a novel orthonairovirus, designated Yezo virus (YEZV), from two patients showing acute febrile illness with thrombocytopenia and leukopenia after tick bite in Hokkaido, Japan, in 2019 and 2020, respectively. YEZV is phylogenetically grouped with Sulina virus detected in Ixodes ricinus ticks in Romania. YEZV infection has been confirmed in seven patients from 2014-2020, four of whom were co-infected with Borrelia spp. Antibodies to YEZV are found in wild deer and raccoons, and YEZV RNAs have been detected in ticks from Hokkaido. In this work, we demonstrate that YEZV is highly likely to be the causative pathogen of febrile illness, representing the first report of an endemic infection associated with an orthonairovirus potentially transmitted by ticks in Japan.
  • Inactivation of SARS-CoV-2 by povidone-iodine products: implications for effective mouth rinsing and gargling
    Hiroaki Kariwa; Hirofumi Sawa; Shintaro Kobayashi
    The Japanese Journal of Veterinary Research, 69, 3, 183, 187, Sep. 2021, [Peer-reviewed], [Lead author, Corresponding author], [Domestic magazines]
    English, Scientific journal
  • DsRNA Sequencing for RNA Virus Surveillance Using Human Clinical Samples.
    Takuma Izumi; Yuhei Morioka; Syun-Ichi Urayama; Daisuke Motooka; Tomokazu Tamura; Takahiro Kawagishi; Yuta Kanai; Takeshi Kobayashi; Chikako Ono; Akinari Morinaga; Takahiro Tomiyama; Norifumi Iseda; Yukiko Kosai; Shoichi Inokuchi; Shota Nakamura; Tomohisa Tanaka; Kohji Moriishi; Hiroaki Kariwa; Tomoharu Yoshizumi; Masaki Mori; Yoshiharu Matsuura; Takasuke Fukuhara
    Viruses, 13, 7, 06 Jul. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Although viruses infect various organs and are associated with diseases, there may be many unidentified pathogenic viruses. The recent development of next-generation sequencing technologies has facilitated the establishment of an environmental viral metagenomic approach targeting the intracellular viral genome. However, an efficient method for the detection of a viral genome derived from an RNA virus in animal or human samples has not been established. Here, we established a method for the efficient detection of RNA viruses in human clinical samples. We then tested the efficiency of the method compared to other conventional methods by using tissue samples collected from 57 recipients of living donor liver transplantations performed between June 2017 and February 2019 at Kyushu University Hospital. The viral read ratio in human clinical samples was higher by the new method than by the other conventional methods. In addition, the new method correctly identified viral RNA from liver tissues infected with hepatitis C virus. This new technique will be an effective tool for intracellular RNA virus surveillance in human clinical samples and may be useful for the detection of new RNA viruses associated with diseases.
  • Development of a highly specific serodiagnostic ELISA for West Nile virus infection using subviral particles.
    Keisuke Maezono; Shintaro Kobayashi; Koshiro Tabata; Kentaro Yoshii; Hiroaki Kariwa
    Scientific reports, 11, 1, 9213, 9213, 28 Apr. 2021, [Peer-reviewed], [Last author], [International Magazine]
    English, Scientific journal, West Nile virus (WNV), a member of the Japanese encephalitis virus (JEV) serocomplex group, causes lethal encephalitis in humans and horses. Because serodiagnosis of WNV and JEV is hampered by cross-reactivity, the development of a simple, secure, and WNV-specific serodiagnostic system is required. The coexpression of prM protein and E protein leads to the secretion of subviral particles (SPs). Deletion of the C-terminal region of E protein is reported to affect the production of SPs by some flaviviruses. However, the influence of such a deletion on the properties and antigenicity of WNV E protein is unclear. We analyzed the properties of full-length E protein and E proteins lacking the C-terminal region as novel serodiagnostics for WNV infection. Deletion of the C-terminal region of E protein suppressed the formation of SPs but did not affect the production of E protein. The sensitivity of an enzyme-linked immunosorbent assay (ELISA) using the full-length E protein was higher than that using the truncated E proteins. Furthermore, in the ELISA using full-length E protein, there was little cross-reactivity with anti-JEV antibodies, and the sensitivity was similar to that of the neutralization test.
  • TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein.
    Mai Kishimoto; Kentaro Uemura; Takao Sanaki; Akihiko Sato; William W Hall; Hiroaki Kariwa; Yasuko Orba; Hirofumi Sawa; Michihito Sasaki
    Viruses, 13, 3, 28 Feb. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein to facilitate cellular entry. Although TMPRSS2 is a well-characterized type II transmembrane serine protease (TTSP), the role of other TTSPs on the replication of SARS-CoV-2 remains to be elucidated. Here, we have screened 12 TTSPs using human angiotensin-converting enzyme 2-expressing HEK293T (293T-ACE2) cells and Vero E6 cells and demonstrated that exogenous expression of TMPRSS11D and TMPRSS13 enhanced cellular uptake and subsequent replication of SARS-CoV-2. In addition, SARS-CoV-1 and SARS-CoV-2 share the same TTSPs in the viral entry process. Our study demonstrates the impact of host TTSPs on infection of SARS-CoV-2, which may have implications for cell and tissue tropism, for pathogenicity, and potentially for vaccine development.
  • ウエストナイルウイルス感染の特異性の高い新規血清診断系の開発
    前園 佳祐; 小林 進太郎; 好井 健太朗; 苅和 宏明
    日本獣医学会学術集会講演要旨集, 163回, 253, 253, (公社)日本獣医学会, Oct. 2020
    Japanese
  • 抗核蛋白質抗体を用いた各種ハンタウイルス抗原の新規検出法の確立
    三橋 健斗; 小林 進太郎; 好井 健太朗; 吉松 組子; 苅和 宏明
    日本獣医学会学術集会講演要旨集, 163回, 253, 253, (公社)日本獣医学会, Oct. 2020
    Japanese
  • ウエストナイルウイルス感染で認められるユビキチンの蓄積に関わるウイルス因子の特定
    小林 進太郎; 川上 怜子; 好井 健太朗; 苅和 宏明
    日本獣医学会学術集会講演要旨集, 163回, 261, 261, (公社)日本獣医学会, Oct. 2020
    Japanese
  • siRNAによるダニ媒介性フラビウイルスの増殖抑制の検討
    深野 紗代; 小林 進太郎; 苅和 宏明; 好井 健太朗
    日本獣医学会学術集会講演要旨集, 163回, 261, 261, (公社)日本獣医学会, Oct. 2020
    Japanese
  • Characterization of tick-borne encephalitis virus isolated from a tick in central Hokkaido in 2017.
    Yuji Takahashi; Shintaro Kobayashi; Mariko Ishizuka; Minato Hirano; Memi Muto; Shoko Nishiyama; Hiroaki Kariwa; Kentaro Yoshii
    The Journal of general virology, 101, 5, 497, 509, May 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Tick-borne encephalitis virus (TBEV) is a zoonotic virus in the genus Flavivirus, family Flaviviridae. TBEV is widely distributed in northern regions of the Eurasian continent, including Japan, and causes severe encephalitis in humans. Tick-borne encephalitis (TBE) was recently reported in central Hokkaido, and wild animals with anti-TBEV antibodies were detected over a wide area of Hokkaido, although TBEV was only isolated in southern Hokkaido. In this study, we conducted a survey of ticks to isolate TBEV in central Hokkaido. One strain, designated Sapporo-17-Io1, was isolated from ticks (Ixodes ovatus) collected in Sapporo city. Sequence analysis revealed that the isolated strain belonged to the Far Eastern subtype of TBEV and was classified in a different subcluster from Oshima 5-10, which had previously been isolated in southern Hokkaido. Sapporo-17-Io1 showed similar growth properties to those of Oshima 5-10 in cultured cells and mouse brains. The mortality rate of mice infected intracerebrally with each virus was similar, but the survival time of mice inoculated with Sapporo-17-Io1 was significantly longer than that of mice inoculated with Oshima 5-10. These results indicate that the neurovirulence of Sapporo-17-Io1 was lower than that of Oshima 5-10. Using an infectious cDNA clone, the replacement of genes encoding non-structural genes from Oshima 5-10 with those from Sapporo-17-Io1 attenuated the neuropathogenicity of the cloned viruses. This result indicated that the non-structural proteins determine the neurovirulence of these two strains. Our results provide important insights for evaluating epidemiological risk in TBE-endemic areas of Hokkaido.
  • Amino acid 159 of the envelope protein affects viral replication and T-cell infiltration by West Nile virus in intracranial infection.
    Shintaro Kobayashi; Chisato Kaneko; Ryoko Kawakami; Rie Hasebe; Hirofumi Sawa; Kentaro Yoshii; Hiroaki Kariwa
    Scientific reports, 10, 1, 7168, 7168, 28 Apr. 2020, [Peer-reviewed], [Last author], [International Magazine]
    English, Scientific journal, West Nile virus (WNV) is an important cause of viral encephalitis in birds and animals, including humans. Amino acid 159 of the envelope (E) protein is reportedly implicated in the different levels of neurovirulence in mice infected with WNV NY99 or Eg101. We investigated the role of amino acid 159 of the E protein in the pathogenesis of WNV infection. We produced recombinant WNV with the structural proteins of the NY99 or Eg101 strain (NY-WT or EgCME-WT) and mutant viruses with substitutions of amino acid 159 of the E protein (NY-E-V159I or EgCME-E-I159V). The NY-WT and NY-E-V159I or EgCME-WT and EgCME-E-I159V titers in culture supernatant were similar. The mortality rate and viral titer in the brains of mice inoculated intraperitoneally with NY-WT or NY-E-V159I were also similar. In contrast, the mortality rate and viral titer in the brains of mice inoculated intracranially with EgCME-E-I159V were significantly higher than those of mice inoculated with EgCME-WT. The numbers of CD3-positive and CD8-positive T cells were greater in brains inoculated with EgCME-E-I159V than in those inoculated with EgCME-WT. Therefore, amino acid 159 of the E protein modulates the pathogenicity of WNV by affecting viral replication and T-cell infiltration in the brain.
  • Meeting report: Eleventh International Conference on Hantaviruses.
    Jan Clement; Clas Ahlm; Tatjana Avšič-Županc; Jason Botten; Kartik Chandran; Colleen B Jonsson; Hiroaki Kariwa; Jonas Klingström; Boris Klempa; Detlev H Krüger; Herwig Leirs; Dexin Li; Mifang Liang; Alemka Markotić; Anna Papa; Connie S Schmaljohn; Nicole D Tischler; Rainer G Ulrich; Antti Vaheri; Cecilia Vial; Richard Yanagihara; Piet Maes
    Antiviral research, 176, 104733, 104733, Apr. 2020, [Invited], [Internationally co-authored], [International Magazine]
    English, Scientific journal, The 2019 11th International Conference on Hantaviruses (ICH 2019) was organized by the International Society for Hantaviruses (ISH), and held on September 1-4, 2019, at the Irish College, in Leuven, Belgium. These ICHs have been held every three years since 1989. ICH 2019 was attended by 158 participants from 33 countries. The current report summarizes research presented on all aspects of hantavirology: ecology; pathogenesis and immune responses; virus phylogeny, replication and morphogenesis; epidemiology; vaccines, therapeutics and prevention; and clinical aspects and diagnosis.
  • Review on counter measures to coronavirus disease 2019 (COVID-19) pandemic, May 2020
    Taishi Kidaka; Sithumini M.W. Lokupathirage; Bungiriye Devinda Shameera Muthusinghe; Boniface Lombe Pongombo; Christida Estu Wastika; Zhouxing Wei; Shizuka Yoshioka; Mayumi Ishizuka; Yoshihiro Sakoda; Hiroaki Kariwa; Norikazu Isoda
    Japanese Journal of Veterinary Research, 68, 3, 133, 150, 2020, [Peer-reviewed]
    Scientific journal
  • West Nile virus capsid protein inhibits autophagy by AMP-activated protein kinase degradation in neurological disease development.
    Shintaro Kobayashi; Kentaro Yoshii; Wallaya Phongphaew; Memi Muto; Minato Hirano; Yasuko Orba; Hirofumi Sawa; Hiroaki Kariwa
    PLoS pathogens, 16, 1, e1008238, Jan. 2020, [Peer-reviewed], [Last author], [International Magazine]
    English, Scientific journal, West Nile virus (WNV) belongs to the Flaviviridae family and has emerged as a significant cause of viral encephalitis in birds and animals including humans. WNV replication directly induces neuronal injury, followed by neuronal cell death. We previously showed that accumulation of ubiquitinated protein aggregates was involved in neuronal cell death in the WNV-infected mouse brain. In this study, we attempted to elucidate the mechanisms of the accumulation of protein aggregates in the WNV-infected cells. To identify the viral factor inducing the accumulation of ubiquitinated proteins, intracellular accumulation of ubiquitinated proteins was examined in the cells expressing the viral protein. Expression of capsid (C) protein induced the accumulation, while mutations at residues L51 and A52 in C protein abrogated the accumulation. Wild-type (WT) or mutant WNV in which mutations were introduced into the residues was inoculated into human neuroblastoma cells. The expression levels of LC3-II, an autophagy-related protein, and AMP-activated protein kinase (AMPK), an autophagy inducer, were reduced in the cells infected with WT WNV, while the reduction was not observed in the cells infected with WNV with the mutations in C protein. Similarly, ubiquitination and degradation of AMPK were only observed in the cells infected with WT WNV. In the cells expressing C protein, AMPK was co-precipitated with C protein and mutations in L51 and A52 reduced the interaction. Although the viral replication was not affected, the accumulation of ubiquitinated proteins in brain and neurological symptoms were attenuated in the mouse inoculated with WNV with the mutations in C protein as compared with that with WT WNV. Taken together, ubiquitination and degradation of AMPK by C protein resulted in the inhibition of autophagy and the accumulation of protein aggregates, which contributes to the development of neurological disease.
  • Serological evidence of Zika virus infection in non-human primates in Zambia.
    Christida E Wastika; Michihito Sasaki; Kentaro Yoshii; Paulina D Anindita; Bernard M Hang'ombe; Aaron S Mweene; Shintaro Kobayashi; Hiroaki Kariwa; Michael J Carr; William W Hall; Yuki Eshita; Yasuko Orba; Hirofumi Sawa
    Archives of virology, 164, 8, 2165, 2170, Aug. 2019, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal, Zika virus (ZIKV) circulation occurs between non-human primates (NHPs) in a sylvatic transmission cycle. To investigate evidence of flavivirus infection in NHPs in Zambia, we performed a plaque reduction neutralization test (PRNT) to quantify neutralizing antibodies. PRNT revealed that sera from NHPs (African green monkeys and baboons) exhibited neutralizing activity against ZIKV (34.4%; 33/96), whereas a PRNT for yellow fever virus using NHP sera showed no neutralization activity. ZIKV genomic RNA was not detected in splenic tissues from NHPs, suggesting that the presence of anti-ZIKV neutralizing antibodies represented resolved infections. Our evidence suggests that ZIKV is maintained in NHP reservoirs in Zambia.
  • Epidemiological survey of tick-borne encephalitis virus infection in wild animals on Hokkaido and Honshu islands, Japan
    Jamsransuren, Dulamjav; Yoshii, Kentaro; Kariwa, Hiroaki; Asakawa, Mitsuhiko; Okuda, Kei; Fujii, Kei; Fukumoto, Shinya; Umemiya-Shirafuji, Rika; Sasaki, Motoki; Matsumoto, Kotaro; Yamaguchi, Emi; Ogawa, Haruko; Imai, Kunitoshi
    Japanese Journal of Veterinary Research, 67, 2, 163, 172, May 2019, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • Serological survey of severe fever with thrombocytopenia syndrome virus infection in Sika deer and rodents in Japan
    Tapiwa Lundu; Kentaro Yoshii; Shintaro Kobayashi; Shigeru Morikawa; Toshio Tsubota; Naoaki Misawa; Daisuke Hayasaka; Hiroaki Kariwa
    Japanese Journal of Veterinary Research, 66, 1, 21, 28, Hokkaido University, 2018, [Peer-reviewed], [Last author], [Domestic magazines]
    English, Scientific journal
  • Targeting of severe fever with thrombocytopenia syndrome virus structural proteins to the ERGIC (endoplasmic reticulum Golgi intermediate compartment) and Golgi complex.
    Tapiwa Lundu; Yoshimi Tsuda; Ryo Ito; Kenta Shimizu; Shintaro Kobayashi; Kentaro Yoshii; Kumiko Yoshimatsu; Jiro Arikawa; Hiroaki Kariwa
    Biomedical research (Tokyo, Japan), 39, 1, 27, 38, Biomedical Research Press, 2018, [Peer-reviewed], [Last author], [Domestic magazines]
    English, Scientific journal, Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) is a newly emerged phlebovirus identified in China, Japan, and South Korea. Phlebovirus glycoproteins (GP) play a key role in targeting viral structural components to the budding compartments in the ER-Golgi intermediate compartment (ERGIC) and Golgi complex. However, the role of SFTSV GP in targeting structural proteins to the ERGIC and Golgi complex remains unresolved. In this study, we show that SFTSV GP plays a significant role in targeting RNA-dependent RNA polymerase (L) and nucleocapsid protein (NP) to the budding sites. Confocal microscopy was used to investigate the subcellular localization of SFTSV structural proteins. In SFTSV-infected cells, GP and L localized to the ER, ERGIC and Golgi complex, whereas NP localized to the ERGIC and Golgi complex. In addition, GP colocalized with L and NP in infected cells. In cells singly transfected with GP, L or NP, GP localized to the same subcellular compartments as in infected cells. However, L or NP alone did not localize to the ER, ERGIC, or Golgi complex. Cotransfection experiments showed that GP altered the localization of L to the ERGIC and Golgi complex but not that of NP. Interestingly, plasmid-expressed NP fused with a hemagglutinin tag localized to the ERGIC and Golgi complex when expressed in SFTSV-infected cells and colocalised with GP, suggesting that GP plays a role in the subcellular localization of L and NP in infected cells. Thus, the SFTSV structural components start to assemble at the ERGIC to Golgi complex. GP is required for transporting L and NP to the ERGIC and Golgi complex. In addition, targeting of NP requires interaction with other factors besides GP.
  • Escape of Tick-Borne Flavivirus from 2'-C-Methylated Nucleoside Antivirals Is Mediated by a Single Conservative Mutation in NS5 That Has a Dramatic Effect on Viral Fitness.
    Ludek Eyer; Hirofumi Kondo; Darina Zouharova; Minato Hirano; James J Valdés; Memi Muto; Tomas Kastl; Shintaro Kobayashi; Jan Haviernik; Manabu Igarashi; Hiroaki Kariwa; Marketa Vaculovicova; Jiri Cerny; Rene Kizek; Andrea Kröger; Stefan Lienenklaus; Milan Dejmek; Radim Nencka; Martin Palus; Jiri Salat; Erik De Clercq; Kentaro Yoshii; Daniel Ruzek
    Journal of virology, 91, 21, 01 Nov. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Dendritic transport of tick-borne flavivirus RNA by neuronal granules affects development of neurological disease.
    Minato Hirano; Memi Muto; Mizuki Sakai; Hirofumi Kondo; Shintaro Kobayashi; Hiroaki Kariwa; Kentaro Yoshii
    Proceedings of the National Academy of Sciences of the United States of America, 114, 37, 9960, 9965, 12 Sep. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • A novel reverse genetics system for production of infectious West Nile virus using homologous recombination in mammalian cells.
    Shintaro Kobayashi; Kentaro Yoshii; Minato Hirano; Memi Muto; Hiroaki Kariwa
    Journal of virological methods, 240, 14, 20, Feb. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • [Rodent associated hantaviruses and hantavirus infections].
    Hiroaki Kariwa
    Uirusu, 67, 1, 25, 32, 2017, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal, Hantaviruses belongs to the genus Hantavirus in the family Bunyaviridae are maintained in rodents and infects to humans by inhalation of the aerosol of infected rodent excreta. In this article, the epidemiology of hantavirus infection and the special relationship between rodent and hantavirus are described. Hantavirus infections include hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). HFRS is characterized high fever, hemorrhage, and renal disorder. HFRS is distributed in East Asia, Europe, and Russia. While HCPS is characterized acute respiratory dysfunction and cardiogenic shock. The distribution of HCPS is limited in North and South Americas. In Japan's neighboring countries, such as Russia, China, and Korea, large numbers of HFRS patients are reported in association with multiple hantaviruses. In Japan, hantavirus infection has not been reported since 1985 but grey red-backed vole (Myodes rufocanus bedfordiae) inhabiting Hokkaido maintain one of the hantaviruses. Coevolution between hantavirus and host may have been occurred during a long period. The endemic areas of hantavirus infection are strongly associated with the distribution of host animal carrying pathogenic hantaviruses.
  • Targeting of severe fever with thrombocytopenia syndrome virus structural proteins to the ERGIC (endoplasmic reticulum Golgi intermediate compartment) and Golgi complex.
    Lundu T; Tsuda Y; Ito R; Shimizu K; Kobayashi S; Yoshii K; Yoshimatsu K; Arikawa J; Kariwa H
    Biomed Res-Tokyo, 78, 8, 1453, 1460, 2017, [Peer-reviewed]
    English
  • HokkaidoウイルスとPuumalaウイルスの遺伝子再集合体の作出とその性状解析
    岩崎 里菜; 真田 崇弘; 好井 健太朗; 苅和 宏明
    日本獣医学会学術集会講演要旨集, 157回, 439, 439, (公社)日本獣医学会, Aug. 2014, [Peer-reviewed]
    Japanese
  • 初代培養マウス脳細胞を用いた脳炎フラビウイルスの増殖機構の解析
    平野 港; 好井 健太朗; 境 瑞樹; 長谷部 理絵; 苅和 宏明
    日本獣医学会学術集会講演要旨集, 156回, 302, 302, (公社)日本獣医学会, Aug. 2013, [Peer-reviewed]
    Japanese
  • 極東型ダニ媒介性脳炎ウイルスの強毒化に関わるウイルス側因子の特定
    境 瑞紀; 好井 健太朗; 寸田 祐嗣; 横澤 香菜; 平野 港; 苅和 宏明
    日本獣医学会学術集会講演要旨集, 156回, 303, 303, (公社)日本獣医学会, Aug. 2013, [Peer-reviewed]
    Japanese
  • 新世界ハンタウイルス感染のためのハンタウイルス組み換え核蛋白を用いた血清型鑑別ELISA法の開発
    駒 貴明; 吉松 組子; 垂石 みどり; 宮下 大輔; 遠藤 理香; 清水 健太; 安田 俊平; 天田 貴子; 瀬戸 隆; 村田 亮; 吉田 喜香; 苅和 宏明; 高島 郁夫; 有川 二郎
    北海道医学雑誌, 88, 1, 35, 35, Jan. 2013
    Japanese, Scientific journal
  • ダニ媒介性フラビウイルスによる中枢神経系障害に関わるウイルス因子の同定
    好井 健太朗; 寸田 祐嗣; 境 瑞紀; 苅和 宏明; Holbrook Michael; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 154回, 264, 264, (公社)日本獣医学会, Aug. 2012, [Peer-reviewed]
    Japanese
  • 極東型ダニ媒介性脳炎ウイルスの強毒化に関わるウイルス側因子の特定
    境 瑞紀; 好井 健太朗; 横澤 香菜; 苅和 宏明
    日本獣医学会学術集会講演要旨集, 154回, 264, 264, (公社)日本獣医学会, Aug. 2012, [Peer-reviewed]
    Japanese
  • ダニ媒介性フラビウイルスのインターフェロンアンタゴニスト作用の解析
    鶴田 征太郎; 好井 健太朗; 境 瑞紀; 苅和 宏明
    日本獣医学会学術集会講演要旨集, 154回, 264, 264, (公社)日本獣医学会, Aug. 2012, [Peer-reviewed]
    Japanese
  • 新たに分離されたHokkaidoウイルスの性状解析
    真田 崇弘; 尾崎 由佳; 瀬戸 隆弘; 中尾 桃子; Saasa Ngonda; 吉松 組子; 有川 二郎; 好井 健太朗; 苅和 宏明
    日本獣医学会学術集会講演要旨集, 154回, 265, 265, (公社)日本獣医学会, Aug. 2012, [Peer-reviewed]
    Japanese
  • 人と動物の共通感染症最前線 9 2008年北海道におけるダニ媒介性脳炎ウイルスの分離と性状解析
    好井健太朗; 山崎翔子; 持舘景太; 苅和宏明; 高島郁夫
    獣医畜産新報, 1090, 377-378, 01 May 2012
    Japanese
  • 日本国内におけるダニ媒介性脳炎の血清疫学調査 (特集 人と動物の共通感染症最前線(8))
    好井 健太朗; 持舘 景太; 苅和 宏明
    獣医畜産新報, 64, 10, 801, 803, 文永堂出版, Oct. 2011
    Japanese
  • ダニ媒介性脳炎ウイルスのE蛋白糖鎖は哺乳動物細胞におけるウイルス粒子分泌に影響する
    柳原 なつみ; 好井 健太朗; 後藤 明子; 伊川 綾恵; 石塚 万里子; 苅和 宏明; 高島 郁夫
    北海道獣医師会雑誌, 55, 8, 415, 415, (公社)北海道獣医師会, Aug. 2011, [Peer-reviewed]
    Japanese
  • 2008年北海道で分離されたダニ媒介性脳炎ウイルスOshima 08-AS株の病原性解析
    山崎 翔子; 好井 健太朗; 真田 崇弘; 苅和 宏明; 高島 郁夫
    北海道獣医師会雑誌, 55, 8, 416, 416, (公社)北海道獣医師会, Aug. 2011, [Peer-reviewed]
    Japanese
  • 2008年北海道で分離されたダニ媒介性脳炎ウイルスOshima 08-AS株の病原性解析
    山崎 翔子; 好井 健太朗; 真田 崇弘; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 152回, 255, 255, (公社)日本獣医学会, Aug. 2011, [Peer-reviewed]
    Japanese
  • 野生マウス由来Oas遺伝子座導入コンジェニックマウスにおけるダニ媒介性脳炎ウイルスの神経病原性の解析
    好井 健太朗; 森藤 可南子; 永田 典代; 佐々木 宣哉; 苅和 宏明; 安居院 高志; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 152回, 256, 256, (公社)日本獣医学会, Aug. 2011, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルスのE蛋白糖鎖は哺乳動物細胞におけるウイルス粒子分泌に影響する
    柳原 なつみ; 好井 健太朗; 石塚 万里子; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 152回, 256, 256, (公社)日本獣医学会, Aug. 2011, [Peer-reviewed]
    Japanese
  • エゾヤチネズミ(Myodes rufocanus)の腎臓由来細胞系の確立とHokkaidoウイルス分離への応用
    真田 崇弘; 瀬戸 隆弘; 尾崎 由佳; Ngonda Saasa; 好井 健太朗; 苅和 宏明
    日本獣医学会学術集会講演要旨集, 152回, 256, 256, (公社)日本獣医学会, Aug. 2011, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎 (特集 ヒトと家畜・ペット・野生動物の感染症--口蹄疫から学ぶ) -- (野生動物と動物由来感染症)
    苅和 宏明; 好井 健太朗; 高島 郁夫
    公衆衛生, 75, 1, 36, 38, 医学書院, Jan. 2011
    Japanese
  • 2008年北海道におけるダニ媒介性脳炎ウイルスの分離と性状解析
    山崎 翔子; 好井 健太朗; 持舘 景太; 村田 亮; 真田 崇弘; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 150回, 247, 247, (公社)日本獣医学会, Sep. 2010, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルスのE蛋白の糖鎖付加がウイルス性状に与える影響
    柳原 なつみ; 好井 健太朗; 後藤 明子; 伊川 綾恵; 石塚 万里子; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 150回, 248, 248, (公社)日本獣医学会, Sep. 2010, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルスSofjin株の感染性cDNAの構築
    高野 絢子; 大森 優紀; 好井 健太朗; 横澤 香菜; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 150回, 248, 248, (公社)日本獣医学会, Sep. 2010, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎/オムスク出血熱のキメラウイルスの作成と性状解析
    好井 健太朗; 寸田 祐嗣; 苅和 宏明; Holbrook Michael; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 150回, 248, 248, (公社)日本獣医学会, Sep. 2010, [Peer-reviewed]
    Japanese
  • メキシコ由来のハンタウイルスに対するモノクローナル抗体の作出と各種ハンタウイルスに対する反応性の検討
    吉田 喜香; 苅和 宏明; 真田 崇弘; Saasa Ngonda; 瀬戸 隆弘; 吉松 組子; 有川 二郎; 好井 健太朗; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 150回, 249, 249, (公社)日本獣医学会, Sep. 2010, [Peer-reviewed]
    Japanese
  • Puumalaウイルスを感染させたシリアンハムスター(Mesocricetus auratus)の感染動態の解析
    真田 崇弘; 苅和 宏明; 谷川 洋一; Nur Hardy Abu Daud; 瀬戸 隆弘; 永田 典代; 吉松 組子; 有川 二郎; 好井 健太朗; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 150回, 252, 252, (公社)日本獣医学会, Sep. 2010, [Peer-reviewed]
    Japanese
  • 人と動物の共通感染症最前線 7 ウエストナイルウイルスの鳥類における増殖性と極東ロシアでの抗体調査
    村田亮; 好井健太朗; 苅和宏明; 高島郁夫
    獣医畜産新報, 1064, 208-209, 01 Mar. 2010
    Japanese
  • ダニ媒介性脳炎〜日本における流行の現状について〜
    好井健太朗; 苅和宏明; 高島郁夫
    北海道獣医師会雑誌, 54, 1, 2-7, 10 Jan. 2010
    Japanese
  • 日本国内におけるダニ媒介性脳炎の血清疫学調査
    持舘 景太; 好井 健太朗; 大森 優紀; 千葉 裕美子; 村田 亮; 真田 崇弘; 前田 潤子; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 148回, 236, 236, (公社)日本獣医学会, Sep. 2009, [Peer-reviewed]
    Japanese
  • 極東ロシアの野鳥におけるウエストナイル熱の血清疫学調査と中和試験の評価
    村田 亮; 橋口 和明; 好井 健太朗; 野田 寛; 伊川 綾恵; 原田 祐里; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 148回, 236, 236, (公社)日本獣医学会, Sep. 2009, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルスSofjin株のレプリコンの構築
    高野 絢子; 大森 優紀; 好井 健太朗; 石塚 万里子; 村田 亮; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 148回, 236, 236, (公社)日本獣医学会, Sep. 2009, [Peer-reviewed]
    Japanese
  • オムスク出血熱ウイルスの感染性cDNAの構築
    好井 健太朗; 苅和 宏明; 高島 郁夫; Holbrook Michael
    日本獣医学会学術集会講演要旨集, 148回, 237, 237, (公社)日本獣医学会, Sep. 2009, [Peer-reviewed]
    Japanese
  • メキシコの野生げっ歯類が保有するハンタウイルスの遺伝子解析
    吉田 喜香; 苅和 宏明; 高野 絢子; 戸谷 理詩; 宮下 大輔; Ngonda Saasa; 瀬戸 隆弘; 真田 崇弘; 吉川 佳佑; 好井 健太朗; 吉松 組子; 有川 次郎; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 148回, 237, 237, (公社)日本獣医学会, Sep. 2009, [Peer-reviewed]
    Japanese
  • 日本国内におけるダニ媒介性脳炎の血清疫学調査
    持舘 景太; 好井 健太朗; 大森 優紀; 千葉 裕美子; 村田 亮; 真田 崇弘; 前田 潤子; 苅和 宏明; 高島 郁夫
    北海道獣医師会雑誌, 53, 8, 111, 111, (公社)北海道獣医師会, Aug. 2009, [Peer-reviewed]
    Japanese
  • 極東ロシアの野鼠からのハンタウイルスの分離と人におけるウイルス感染状況の調査
    吉川 佳佑; 苅和 宏明; 瀬戸 隆弘; 真田 崇弘; 石塚 万里子; 吉松 組子; 有川 二郎; Ivanov Leonid; Slonova Raisa; 好井 健太朗; 高島 郁夫
    北海道獣医師会雑誌, 53, 8, 112, 112, (公社)北海道獣医師会, Aug. 2009, [Peer-reviewed]
    Japanese
  • 極東ロシアのげっ歯類からのハンタウイルスの分離とウイルス遺伝子の性状解析
    吉川 佳佑; 苅和 宏明; 瀬戸 隆弘; 真田 崇弘; 石塚 万里子; 吉松 組子; 有川 二郎; Ivanov Lenid; 好井 健太朗; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 147回, 260, 260, (公社)日本獣医学会, Mar. 2009, [Peer-reviewed]
    Japanese
  • ウエストナイル熱の血清診断法の評価と極東ロシアにおける疫学調査
    村田 亮; 橋口 和明; 好井 健太朗; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 146回, 225, 225, (公社)日本獣医学会, Sep. 2008, [Peer-reviewed]
    Japanese
  • 多種類のハンタウイルス血清型の検出が可能な抗原検出法の開発
    真田 崇弘; 苅和 宏明; 瀬戸 隆弘; 谷川 洋一; 宮下 大輔; 吉松 組子; 有川 二郎; 好井 健太朗; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 146回, 225, 225, (公社)日本獣医学会, Sep. 2008, [Peer-reviewed]
    Japanese
  • ウイルス様粒子を用いたダニ媒介性脳炎の新たな診断法の開発
    千葉 裕美子; 伊川 綾恵; 好井 健太朗; 大森 優紀; 村田 亮; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 146回, 226, 226, (公社)日本獣医学会, Sep. 2008, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルスの中空ウイルス様粒子のワクチンへの応用
    大森 優紀; 伊川 綾恵; 川上 和江; 好井 健太朗; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 146回, 226, 226, (公社)日本獣医学会, Sep. 2008, [Peer-reviewed]
    Japanese
  • SARSコロナウイルスのNおよびM蛋白質の粒子形成における機能解析
    中内 美名; 藤井 寛子; 苅和 宏明; 前田 秋彦; 好井 健太朗; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 145回, 204, 204, (公社)日本獣医学会, Mar. 2008, [Peer-reviewed]
    Japanese
  • ウエストナイルウイルスのE蛋白上糖鎖が宿主内におけるウイルス増殖に与える影響
    村田 亮; 好井 健太朗; 苅和 宏明; 江下 優樹; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 145回, 205, 205, (公社)日本獣医学会, Mar. 2008, [Peer-reviewed]
    Japanese
  • Arch Virol
    Nakamura, I; Yoshimatsu, K; Lee, B. H; Okumura, M; Taruishi, M; Araki, K; Kariwa, H; Takashima, I; Arikawa, J
    Development of a serotyping ELISA system for Thailand virus infection., 153, 1537, 1542, 2008
  • ウエストナイルウイルスのE蛋白上糖鎖付加がウイルス増殖に与える影響
    村田 亮; 好井 健太朗; 原田 祐里; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 144回, 127, 127, (公社)日本獣医学会, Aug. 2007, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルスのウイルス様粒子およびその組換え発現プラスミドを抗原とした針無加圧式注射によるワクチン接種の有効性の検討
    大森 優紀; 伊川 綾恵; 川上 和江; 好井 健太朗; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 144回, 128, 128, (公社)日本獣医学会, Aug. 2007, [Peer-reviewed]
    Japanese
  • レプリコンを利用したウエストナイルウイルスとダニ媒介性脳炎ウイルスのキメラウイルス様粒子の作製
    原田 祐里; 好井 健太朗; 伊川 綾恵; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 142回, 121, 121, (公社)日本獣医学会, Aug. 2006, [Peer-reviewed]
    Japanese
  • 家畜と野生動物における人と動物の共通感染症 齧歯類とハンタウイルス感染症
    苅和宏明; 谷川洋一; 萩谷友洋; LOKUGAMAGE Kumari; LOKUGAMAGE Nandadeva; DAUD Nur Hardy Bin Abu; 好井健太朗; 高島郁夫
    獣医畜産新報, 59, 1021, 633-638, 638, 文永堂出版, 01 Aug. 2006
    Japanese
  • ウイルス様粒子を用いたフラビウイルスの粒子形成機構の解析,および診断法・予防法開発への応用
    好井 健太朗; 後藤 明子; 小原 真弓; 川上 和江; 伊川 綾江; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 141回, 73, 73, (公社)日本獣医学会, Mar. 2006, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルス組み換え蛋白を用いたELISA法による野鼠血清スクリーニング法の開発
    伊川 綾恵; 好井 健太朗; 川上 和江; 後藤 明子; 小原 真弓; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 140回, 147, 147, (公社)日本獣医学会, Aug. 2005, [Peer-reviewed]
    Japanese
  • 人獣共通感染症 日本と極東ロシアのダニ媒介性脳炎ウイルスの系統解析と病原性
    高島 郁夫; 早坂 大輔; 後藤 明子; 好井 健太朗; 苅和 宏明
    ウイルス, 55, 1, 35, 44, 日本ウイルス学会, Jun. 2005, [Peer-reviewed]
    Japanese
  • 人と動物の共通感染症の最前線 2 東アジアの人とげっ歯類におけるハンタウイルス感染の疫学的研究
    有川二郎; 吉松組子; KUMPERASART Sanit; THANG Truong Thua; 荒木幸一; LEE Byoung‐Hee; KRUGER Detlev H; 苅和宏明; 高島郁夫
    獣医畜産新報, 1005, 326, 328, 01 Apr. 2005
    Japanese
  • 野生げっ歯類からのハンタウイルス抗原検出用ELISAの開発
    谷川 洋一; 苅和 宏明; 萩谷 友洋; Lokugamage Nandadeva; Lokugamage Kumari; 舘 敦史; 好井 健太朗; 吉松 組子; 有川 二郎; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 139回, 185, 185, (公社)日本獣医学会, Mar. 2005, [Peer-reviewed]
    Japanese
  • フラビウイルスのウイルス粒子分泌におけるユビキチン-プロテアソーム系の関与
    好井 健太朗; 後藤 明子; 川上 和江; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 138回, 129, 129, (公社)日本獣医学会, Aug. 2004, [Peer-reviewed]
    Japanese
  • 日本におけるハンタウイルス感染の動物伝染病学的及び疫学的研究(Epizootiological and epidemiological study of hantavirus infection in Japan)
    Lokugamage Nandadeva; 苅和 宏明; 好井 健太朗; 舘 敦史; 安藤 秀二; 福島 博; 土屋 公幸; 岩崎 琢也; 吉松 組子; 有川 二郎; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 138回, 130, 130, (公社)日本獣医学会, Aug. 2004, [Peer-reviewed]
    English
  • タイリクヤチネズミから分離されたPuumala型近縁ハンタウイルスの遺伝子解析
    谷川 洋一; 苅和 宏明; Lokugamage Nandadeva; 萩谷 友洋; Lokugamage Kumari; 舘 敦史; 好井 健太朗; 岩佐 真宏; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 138回, 130, 130, (公社)日本獣医学会, Aug. 2004, [Peer-reviewed]
    Japanese
  • Amur型ハンタウイルス糖蛋白の哺乳類細胞での発現と抗原性解析
    舘 敦史; 苅和 宏明; Lokugamage Kumari; Lokugamage Nandadeva; 谷川 洋一; 好井 健太朗; 吉松 組子; 有川 二郎; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 138回, 131, 131, (公社)日本獣医学会, Aug. 2004, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルス組み替え蛋白を用いたELISAによる野ネズミ血清スクリーニング法の開発
    川上 和江; 好井 健太朗; 後藤 明子; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 137回, 114, 114, (公社)日本獣医学会, Mar. 2004, [Peer-reviewed]
    Japanese
  • repliconを利用したフラビウイルスのキメラウイルス様粒子の作成
    好井 健太朗; 早坂 大輔; 後藤 明子; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 137回, 114, 114, (公社)日本獣医学会, Mar. 2004, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルスのE蛋白の糖鎖修飾がウイルス粒子分泌に与える影響
    後藤 明子; 好井 健太朗; 小原 真弓; 植木 智隆; 水谷 哲也; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 137回, 115, 115, (公社)日本獣医学会, Mar. 2004, [Peer-reviewed]
    Japanese
  • 50 Activation of INK suppresses apoptosis in C6/36 cells
    Mizutani T.; Eshita Y.; Ako Y.; Miyoshi H.; Kariwa H.; Takashima I.
    Medical Entomology and Zoology, 55, 56, 56, The Japan Society of Medical Entomology and Zoology, 2004
    Japanese
  • ダニ媒介性脳炎ウイルスの感染性cDNAクローンを用いた病原性解析
    植木 智隆; 早坂 大輔; 後藤 明子; 好井 健太朗; 水谷 哲也; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 136回, 176, 176, (公社)日本獣医学会, Sep. 2003, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルスのrepliconおよびpackaging systemの構築
    好井 健太朗; 早坂 大輔; 後藤 明子; 水谷 哲也; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 136回, 257, 257, (公社)日本獣医学会, Sep. 2003, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルスのエンベロープ糖蛋白の糖鎖欠損がウイルス粒子形成に与える影響
    後藤 明子; 好井 健太朗; 小原 真弓; 植木 智隆; 水谷 哲也; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 135回, 156, 156, (公社)日本獣医学会, Mar. 2003, [Peer-reviewed]
    Japanese
  • A06 Inhibition of West Nile virus infection on Aedes albopictus cell line, C6/36 : The role of JNK signaling pathway on virus infection
    Mizutani T.; Kobayashi M.; Eshita Y.; Shirato K.; Ako Y.; Miyoshi H.; Kariwa H.; Takashima I.
    Medical Entomology and Zoology, 54, 24, 24, The Japan Society of Medical Entomology and Zoology, 2003
    Japanese
  • ダニ媒介性脳炎ウイルスのウイルス粒子放出抑制に関する解析
    好井 健太朗; 後藤 明子; 小原 真弓; 植木 智隆; 早坂 大輔; 水谷 哲也; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 134回, 195, 195, (公社)日本獣医学会, Aug. 2002, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルス神経侵入性弱毒変異株のマウス体内での動態
    後藤 明子; 好井 健太朗; 早坂 大輔; 水谷 哲也; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 134回, 195, 195, (公社)日本獣医学会, Aug. 2002, [Peer-reviewed]
    Japanese
  • 北海道におけるダニ媒介性脳炎ウイルスの血清疫学調査
    小原 真弓; 好井 健太朗; 後藤 明子; 早坂 大輔; 水谷 哲也; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 134回, 195, 195, (公社)日本獣医学会, Aug. 2002, [Peer-reviewed]
    Japanese
  • Evaluation of European tick-borne encephalitis virus vaccine against recent Siberian and far-eastern subtype strains
    Daisuke Hayasaka; Akiko Goto; Kentaro Yoshii; Tetsuya Mizutani; Hiroaki Kariwa; Ikuo Takashima
    Vaccine, 19, 32, 4774, 4779, Sep. 2001
    English, Scientific journal
  • Truncated hantavirus nucleocapsid proteins for serotyping Hantaan, Seoul, and Dobrava hantavirus infections.
    Araki K; Yoshimatsu K; Ogino M; Ebihara H; Lundkvist A; Kariwa H; Takashima I; Arikawa J
    Journal of clinical microbiology, 39, 2397, 2404, 7, Jul. 2001, [Peer-reviewed]
  • Epidemiology and epizootiology of hantavirus infection in Japan.
    Arikawa J; Yoshimatsu K; Kariwa H
    Japanese journal of infectious diseases, 54, 95, 102, 3, Jun. 2001, [Peer-reviewed]
  • Distribution and characterization of tick-borne encephalitis viruses in Siberia and far-eastern region
    Daisuke Hayasaka; Leonid Ivanov; Galina N. Leonova; Akiko Goto; Kentaro Yoshii; Tetsuya Mizutani; Hiroaki Kariwa; Ikuo Takashima
    J. Gen. Virol., 82, Pt6, 1319, 1328, Society for General Microbiology., Jun. 2001
    English, Scientific journal, In this study, tick-borne encephalitis (TBE) viruses from Siberia and far-eastern Asia were characterized in order to determine virus subtype distribution. TBE viruses were isolated from ticks (Ixodes persulcatus) collected in the far-eastern (Khabarovsk and Vladivostok) and Siberian (Irkutsk) regions of Russia in 1999. Phylogenetic analysis showed that isolates formed distinct clusters of far-eastern and Siberian subtypes. There was also a minor difference in antigenicity between the Irkutsk isolates and other TBE virus strains, as demonstrated by the reactivity of monoclonal antibodies. Amino acid alignments of the E gene showed that the Irkutsk isolates had a single amino acid change at position 234 (Q or H); this amino acid position is considered to be a 'signature' of Siberian subtype TBE viruses. Strains isolated in Irkutsk also exhibited equivalent or somewhat higher virulence in mice compared with far-eastern TBE virus isolates. All viruses isolated in this study (i.e. far-east Asian and Siberian isolates) have 3' non-coding regions (NCRs) of almost the same length, which contrasts with the various sizes of 3'NCRs of other TBE viruses strains reported previously. The data presented in this study show that the 3'NCR is uniform among TBE viruses isolated from Siberia and far-eastern Asia and that the 3'NCR is essential for TBE virus growth in tick and/or rodent host cells.
  • Characterization of in vitro and in vivo antiviral activity of lactoferrin and ribavirin upon hantavirus
    Michael E. Murphy; Hiroaki Kariwa; Tetsuya Mizutani; Hiroki Tanabe; Kumiko Yoshimatsu; Jiro Arikawa; Ikuo Takashima
    J Vet Med Sci., 63, 6, 637, 645, Japanese Society of Veterinary Science, Jun. 2001
    English, Scientific journal, Mechanisms of anti-hantaviral activities of bovine lactoferrin (LF) and ribavirin (Rbv) were investigated. Hantavirus focus formation at 48 hr was 15% of the control in cells treated with 400μg/ml LF for 1 hr at 37℃ prior to viral infection. Post infection treatment with 100 μg/ml Rbv also inhibited the focus formation to 2.5% of the control. Combined LF pre- and Rbv post-infection treatment completely inhibited focus formation. Viral glycoprotein (G2) and nucleocapsid protein (NP) syntheses were delayed in LF pre-treated cells up to 24 hr post infection (hpi) but became comparable to the control by 48 hpi. Further, LF inhibited viral shedding at 24 hpi but did not inhibit shedding after 48 hpi. However, Rbv was able to inhibit synthesis of viral proteins, (+) and (-) stand RNAs also inhibited viral shedding after 24 hr. These results suggest that LF inhibits viral adsorption to cells, while Rbv inhibits viral RNA synthesis. For in vivo trials of LF and Rbv, LF pre- and Rbv post-treatment were evaluated in suckling mice infected with hantavirus, of which 7% survived. LF concentrations of 40 and 160 mg/kg administered prior to viral challenge improved survival rates to 15% and 70%, respectively for single administration and 85% and 94%, respectively, for double administration. Rbv concentrations of 25 and 50 mg/kg gave survival rates of 68% and 81%, respectively. This suggests that both LF and Rbv are efficacious in hantavirus infection in vivo.
  • ダニ媒介性脳炎(TBE)ウイルスシベリア型及び極東型の病原性の比較とワクチンの効果
    早坂 大輔; 後藤 明子; 好井 健太朗; 水谷 哲也; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 131回, 121, 121, (公社)日本獣医学会, Mar. 2001, [Peer-reviewed]
    Japanese
  • ダニ媒介性脳炎ウイルス組み換え蛋白の作成と抗原性状の解析
    好井 健太朗; 早坂 大輔; 後藤 明子; 水谷 哲也; 苅和 宏明; 高島 郁夫
    日本獣医学会学術集会講演要旨集, 131回, 121, 121, (公社)日本獣医学会, Mar. 2001, [Peer-reviewed]
    Japanese
  • Epidemiology of tick-borne encephalitis (TBE) and phylogenetic analysis of TBE viruses in Japan and Far Eastern Russia
    Ikuo Takashima; Daisuke Hayasaka; Akiko Goto; Hiroaki Kariwa; Tetsuya Mizutani
    Jpn J Infect Dis., 54, 1, 1, 11, Jan. 2001
    English
  • Epidemiology of Arbovirus Infection
    TAKASHIMA Ikuo; HAYASAKA Daisuke; KARIWA Hiroaki
    Journal of the Japan Veterinary Medical Association, 53, 12, 793, 799, Japan Veterinary Medical Association, 20 Dec. 2000
    Japanese
  • In vitro antiviral activity of lactoferrin and ribavirin upon hantavirus
    Michael E. Murphy; Hiroaki Kariwa; Tetsuya Mizutani; Kumiko Yoshimatsu; Jiro Arikawa; Ikuo Takashima
    Arch. Virol., 145, 8, 1571, 1582, Aug. 2000
    English, Scientific journal
  • The mechanism of actinomycin D-mediated increasing of Borna disease virus (BDV) RNA in persistently BDV-infected cells
    Tetsuya Mizutani; Hisae Inagaki; Mitsuhiro Tada; Daisuke Hayasaka; Michael E. Murphy; Toshiyoshi Fujiwara; Jun-ichi Hamada; Hiroaki Kariwa; Ikuo Takashima
    Microbirol. Immunol., 44, 7, 597, 603, Jul. 2000
    English, Scientific journal
  • Characterization of monoclonal antibodies against Hokkaido strain tick-borne encephalitis virus
    Kimiyo Komoro; Daisuke Hayasaka; Tetsuya Mizutani; Hiroaki Kariwa; Ikuo Takashima
    Microbiol Immunol., 44, 6, 533, 536, Center for Academic Pub. Japan, Jun. 2000
    English, Scientific journal
  • Detection of hantaviral antibodies among patients with hepatitis of unknown etiology in Japan
    Hiroaki Kariwa; Kumiko Yoshimatsu; Kouichi Araki; Chayama K; Kumada H; Michiko Ogino; Ebihara H; Michael E. Murphy; Tetsuya Mizutani; Ikuo Takashima; Jiro Arikawa
    Microbiol Immunol., 44, 5, 357, 362, Center for Academic Pub. Japan, May 2000
    English, Scientific journal
  • Phylogenetic and virulence analysis of Tick-borne encephalitis viruses from Japan and Far East Russia
    Daisuke Hayasaka; Yoshiyuki Suzuki; Hiroaki Kariwa; Leonid Ivanov; Vladimir Volkov; Vladimir Demenev; Tetsuya Mizutani; Takashi Gojobori; Ikuo Takashima
    J. Gen. Virol., 80, Pt12, 3127, 3135, Society for General Microbiology, Dec. 1999
    English, Scientific journal, We have previously reported that tick-borne encephalitis (TBE) is endemic in a specific area of Hokkaido, Japan. In Oshima, the southern part of Hokkaido, TBE virus was isolated from sentinel dogs, ticks and rodents in 1995 and 1996. To identify when these TBE viruses emerged in Hokkaido, the times of divergence of TBE virus strains isolated in Oshima and far-eastern Russia were estimated. TBE virus was isolated in Khabarovsk in 1998 and the nucleotide sequences of viral envelope protein genes of isolates from Oshima and Khabarovsk were compared. From the synonymous substitution rate of these virus strains, the lineage divergence time of these TBE virus strains was predicted phylogenetically to be about 260–430 years ago. Furthermore, the virulence of TBE virus isolates from Oshima and Khabarovsk were compared in a mouse model. The results showed that the isolates possessed very similar virulence in mice. This report provides evidence that the Oshima strains of TBE virus in Hokkaido emerged from far-eastern Russia a few hundred years ago and this explains why these strains possess virulence similar to the TBE viruses isolated in Russia.
  • Enhancement of Borna Disease Virus Transcription in Persistently Infected Cells by Serum Starvation
    Tetsuya Mizutani; Hisae Inagaki; Daisuke Hayasaka; Hiroaki Kariwa; Ikuo Takashima
    Journal of Veterinary Medical Science, 61, 7, 831, 834, Jul. 1999, [Peer-reviewed]
    English, Scientific journal
  • Enhancement of Borna disease virus transcription in persistently infected cells by serum starvation
    Tetsuya Mizutani; Hisae Inagaki; Daisuke Hayasaka; Hiroaki Kariwa; Ikuo Takashima
    J. Vet. Med. Sci., 61, 7, 831, 834, Japanese Society of Veterinary Science, Jul. 1999
    English, Scientific journal, Transcription of Borna disease virus (BDV) in persistently infected MDCK (MDCK/BDV) cells increased in the fatal bovine serum free media as detected by Northern blot analysis. Especially, the amount of 1.9-kb RNA without cap formation at the 5' end and polyadenylation at the 3' end, increased as compared to other mRNA molecules of BDV. Growth arrest of MDCK/BDV cells observed in the condition of serum starvation might be important for increasing viral transcription. Since N-cadherin is the responsible factor for cell to-cell contact, MDCK/BDV cells were cultured in calcium free medium which inhibits the interaction of N-cadherin. However, inhibition of cell-to-cell contact by N-cadlnerin is not effective on up regulation of viral transcription. Our finding in this study indicates that enhancement of BDV transcription by serum starvation is a useful technique for further investigation in understanding of mechanisms of BDV transcription.
  • 腎症候性出血熱
    苅和宏明; 水谷哲也; 高島郁夫
    「最新医学」 6月増刊号, 54, 1425, 1431, Jun. 1999
    Japanese
  • Protection against tick-borne encephalitis virus isolated in Japan by active and passive immunization
    Nobuyuki Chiba; Mihoro Osada; Kimiyo Komoro; Tetsuya Mizutani; Hiroaki Kariwa; Ikuo Takashima
    Vaccine, 17, 11-12, 1532, 1539, Mar. 1999
    English, Scientific journal
  • A Serosurvey of Borna Disease Virus Infection in Wild Rats by a Capture ELISA
    Koji Tsujimura; Tetsuya Mizutani; Hiroaki Kariwa; Kumiko Yoshimatsu; Michiko Ogino; Yuko Morii; Hisae Inagaki; Jiro Arikawa; Ikuo Takashima
    Journal of Veterinary Medical Science, 61, 2, 113, 117, Feb. 1999, [Peer-reviewed]
    English, Scientific journal
  • Single-step reverse transcriptase polymerase chain reaction for detection of Borna disease virus RNA in vitro and in vivo
    T Mizutani; M Ogino; Y Nishino; T Kimura; H Inagaki; D Hayasaka; H Kariwa; Takashima, I
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 46, 4, 165, 169, Feb. 1999, [Peer-reviewed]
    English, Scientific journal
  • Pathogenicity of tick-borne encephalitis virus isolated in Hokkaido, Japan in mouse model
    Nobuyuki Chiba; Takuya Iwasaki; Tetsuya Mizutani; Hiroaki Kariwa; Takeshi Kurata; Ikuo Takashima
    Vaccine, 17, 7-8, 779, 787, Feb. 1999
    English, Scientific journal
  • A serosurvey of Borna disease virus infection in wild rats by a capture ELISA
    Koji Tsujimura; Tetsuya Mizutani; Kumiko Yoshimatsu; Michiko Oginio; Yuko Morii; Hisae Inagaki; Jiro Arikawa; Hiroaki Kariwa; Ikuo Takashima
    J. Vet. Med. Sci., 61, 2, 113, 117, Japanese Society of Veterinary Science, Feb. 1999
    English, Scientific journal, For a serological diagnostic test for Borna disease (BD), we developed a capture ELISA with specificity and sensitivity based on detection of antibodies against BD virus (BDV) p40 protein. Using our capture ELISA system, the antibody response of rats inoculated intracerebrally with BDV at 4 weeks after birth showed a sharp increase from 1 to 4 weeks postinoculation (p.i.) and a steady level after 5 weeks p.i. To investigate prevalence of BDV infection among wild rats, we examined sera of Rattus norvegicus in Kami-iso town, Oshima district, Hokkaido, suggesting that rats in this area had not been infected by BDV.
  • Transcriptional control of Borna disease virus (BDV) in persistently BDV-infected cells
    T Mizutani; H Inagaki; D Hayasaka; S Shuto; N Minakawa; A Matsuda; H Kariwa; Takashima, I
    ARCHIVES OF VIROLOGY, 144, 10, 1937, 1946, 1999, [Peer-reviewed]
    English, Scientific journal
  • Reverse transcriptase-nested polymerase chain reaction for detecting p40 RNA of Borna disease virus, without risk of plasmid contamination
    Tetsuya Mizutani; Yoshii Nishino; Hiroaki Kariwa; Ikuo Takashima
    J. Vet. Med. Sci., 61, 1, 77, 80, JAPANESE SOCIETY OF VETERINARY SCIENCE, Jan. 1999
    English, Scientific journal, Several methods for the detection of Borna disease virus (BDV) RNA have been reported, one being the reverse transcription-nested polymerase chain reaction (RT-nested PCR) method. However, due to the possibility of contamination of the cloned DNA in a reaction tube, false-positive results might be obtained by RT-nested PCR. To detect only BDV RNA without anxiety of contamination, we developed an RT-nested PCR system using "mRNA selective PCR kit". Using this system, cDNA of BDV p40 in the plasmid (up to 5 × 107 molecules) was not amplified. BDV specific sequence was amplified from total RNA (more than 50 pg) of MDCK/BDV cells, which were persistently infected with BDV. These results indicate that this mRNA selective RT-nested PCR system can specifically amplify target RNA as distinguished from plasmid contaminated.
  • Research on epidemiological study on acarine encephalitis and establishment of prevention method by vaccine.
    TAKASHIMA IKUO; ARIKAWA JIRO; KARIWA HIROAKI; NEURA TETSUYA
    北海道の研究開発, 1998, 95, 100, Dec. 1998
    Japanese
  • A single-tube RT-PCR method for the detection of Borna disease viral genomic RNA.
    Mizutani T; Ogino M; Nishino Y; Kimura T; Kariwa H; Tsujimura K; Inagaki H; Takashima I
    The Japanese journal of veterinary research, 46, 2, 73, 81, 2-3, Nov. 1998, [Peer-reviewed]
    English, For detecting Borna disease virus (BDV) genomic stranded RNA, single-tube reverse transcription-polymerase chain reaction (St RT-PCR) was developed to equal the sensitivity of RT-nested PCR but with reduced risk of contamination. BDV-genomic stranded RNA was synthesized in vitro using plasmid cDNA of BDV p24 region as a template and RNA was also extracted from BDV-persistently infected MDCK (MDCK/BDV) cells. Both RNAs were amplified by St RT-PCR in which a single round of RT and a single round of PCR were performed in the same tube. Ten copies of synthesized RNA could be amplified by St RT-PCR, indicating that St RT-PCR method is as sensitive as the ordinary RT-nested PCR method. Furthermore, this method was applied to quantify the exact copy number of genomic RNA in MDCK/BDV cells. Signals were obtained from the samples containing more than 1 pg total cellular RNA. From the results, approximately 100 copies of BDV genomic RNA exist in one MDCK/BDV cell. BDV genomic RNA from the in vivo RNA samples using St RT-PCR, indicating this method is applicable for the epidemiological study of BDV without contamination.
  • Inhibition of Borna disease virus replication by Ribavirin in persistently infected cells
    Tetsuya Mizutani; Hisae Inagaki; Koichi Araki; Hiroaki Kariwa; Jiro Arikawa; Ikuo Takashima
    Arch. Virol., 143, 10, 2039, 2044, Oct. 1998
    English, Scientific journal
  • Antigenic characterization of Hantaan and Seoul virus nucleocapsid proteins expressed by recombinant baculovirus: Application of a truncated protein, lacking an antigenic region common to the two viruses, as a serotyping antigen
    M Morii; K Yoshimatsu; J Arikawa; GZ Zhou; H Kariwa; Takashima, I
    JOURNAL OF CLINICAL MICROBIOLOGY, 36, 9, 2514, 2521, Sep. 1998, [Peer-reviewed]
    English, Scientific journal
  • Urine-associated horizontal transmission of Seoul virus among rats
    H Kariwa; M Fujiki; K Yoshimatsu; J Arikawa; Takashima, I; N Hashimoto
    ARCHIVES OF VIROLOGY, 143, 2, 365, 374, 1998, [Peer-reviewed]
    English, Scientific journal
  • Laboratory of Public Health
    Takashima, I; H Kariwa; T Mizutani
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 45, 3, 176, 177, Nov. 1997, [Peer-reviewed]
    English, Scientific journal
  • Experimental Chlamydia psittaci infection of Japanese quail
    Takashima, I; M Hiyoshi; H Kariwa; R Mukaiya; N Hashimoto
    MICROBIOLOGY AND IMMUNOLOGY, 40, 4, 265, 270, 1996, [Peer-reviewed]
    English, Scientific journal
  • Modes of Seoul virus infections: persistency in newborn rats and transiency in adult rats.
    Kariwa H; Kimura M; Yoshizumi S; Arikawa J; Yoshimatsu K; Takashima I; Hashimoto N
    Archives of virology, 141, 12, 2327, 2338, 12, 1996, [Peer-reviewed]
  • Production of recombinant hantavirus nucleocapsid protein expressed in silkworm larvae and its use as a diagnostic antigen in detecting antibodies in serum from infected rats.
    Yoshimatsu K; Arikawa J; Yoshida R; Li H; Yoo YC; Kariwa H; Hashimoto N; Kakinuma M; Nobunaga T; Azuma I
    Laboratory animal science, 45, 641, 646, 6, Dec. 1995, [Peer-reviewed]
  • Evidence for the existence of Puumula-related virus among Clethrionomys rufocanus in Hokkaido, Japan.
    Kariwa H; Yoshizumi S; Arikawa J; Yoshimatsu K; Takahashi K; Takashima I; Hashimoto N
    The American journal of tropical medicine and hygiene, 53, 222, 227, 3, Sep. 1995, [Peer-reviewed]
  • Characterization of the mode of Hantaan virus infection in adult mice using a nested reverse transcriptase polymerase chain reaction: transient virus replication in adult mice.
    Kariwa H; Kamimura M; Arikawa J; Yoshimatsu K; Takashima I; Hashimoto N
    Microbiology and immunology, 39, 1, 35, 41, 1, 1995, [Peer-reviewed]
    English
  • Enhancement of infectivity of hantavirus in cell culture by centrifugation.
    Kariwa H; Arikawa J; Takashima I; Isegawa Y; Yamanishi K; Hashimoto N
    Journal of virological methods, 49, 2, 235, 244, 2, Sep. 1994, [Peer-reviewed]
  • Comparison of nucleotide sequences of M genome segments among Seoul virus strains isolated from eastern Asia.
    Kariwa H; Isegawa Y; Arikawa J; Takashima I; Ueda S; Yamanishi K; Hashimoto N
    Virus research, 33, 1, 27, 38, 1, Jul. 1994, [Peer-reviewed]
  • KINETICS AND CROSS-REACTIVITY OF THE VIRUS-SPECIFIC ANTIBODY-FORMING-CELLS IN MICE DURING PRIMARY AND SECONDARY INFECTION WITH JAPANESE ENCEPHALITIS-VIRUS AND RELATED FLAVIVIRUSES
    JG GARCIA; TAKASHIMA, I; H KARIWA; N HASHIMOTO
    JOURNAL OF VIROLOGICAL METHODS, 48, 1, 31, 41, Jun. 1994, [Peer-reviewed]
    English, Scientific journal
  • Epizootiological studies of hantavirus infection among urban rats in Hokkaido, Japan: evidences for the persistent infection from the sero-epizootiological surveys and antigenic characterizations of hantavirus isolates.
    Arikawa J; Ito M; Yao JS; Kariwa H; Takashima I; Hashimoto N
    The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 56, 1, 27, 32, 1, Feb. 1994, [Peer-reviewed]
    English, Epizootiological studies of hantavirus infection among urban rats were carried out through the surveys repeated 11 times at the same dumping ground area in 1983 to 1988. A total of 279 rats (Rattus norvegicus) were captured during the surveys. Sero-positive animals to hantavirus strain SR-11 were detected in all the surveys. Overall positive rate of rats 6 months old or more (94/128, 73.4%) was significantly higher than that of younger rats (23/151, 15.2%, x^2=96.4, P<0.001). Therefore, age dependent acquisition of hantavirus infection among rats was confirmed. Seven hantavirus strains, KI-83-262 (August, in 1983, designated as strain KI-262 in our previous report (2)), KI-85-1 and 85-2 (July in 1985), KI-88-4, 88-11, 88-15 and 88-24 (October, 1988) were isolated from lung tissues of adult rats which have high titers of neutralizing antibody. Although the serum specimens of virus carrier rats neutralized the infectivity of all the KI isolates, no apparent antigenic change in the isolates was detected by indirect immunofluorescent antibody (IFA) assay using polyclonal and monoclonal antibodies (MAbs) regardless of isolation years. However, neutralization test showed slight difference of antigenicity among KI strains. These results epizootiologically confirmed that hantavirus infected persistently among urban rats in a presence of neutralizing antibody.
  • Application of a recombinant baculovirus expressing hantavirus nucleocapsid protein as a diagnostic antigen in IFA test: cross reactivities among 3 serotypes of hantavirus which causes hemorrhagic fever with renal syndrome (HFRS).
    Yoshimatsu K; Arikawa J; Kariwa H
    The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 55, 6, 1047, 1050, 6, Dec. 1993, [Peer-reviewed]
    English, Recombinant baculovirus-infected insect cells which expressed recombinant protein, analogous to the nucleocapsid protein (NP) of Seoul type hantavirus, strain SR-11 (rNP-SR-Sf9) were applied to the indirect immunofluorescent antibody (IFA) test. The rNP-SR-Sf9 reacted with anti NP MAb clones which recognized strain specific or hantavirus common epitopes in the IFA test. The recombinant antigen was detected by antibodies to 3 serotypes of hantaviruses (Hantaan 76-118, SR-11, Puumala). Antibody titers of a group of experimentally infected mouse and urban rat sera using rNP-SR-Sf9 and strain SR-11-infected Vero cell antigens were mutual correlative. These results indicated that the rNP-SR-Sf9 were an effective and safety substitute for Vero E6 cells in the IFA test for serosurveys of hantavirus infection.
  • IMPROVED SENSITIVITY IN THE ANTIBODY-FORMING CELL ASSAY FOR JAPANESE ENCEPHALITIS-VIRUS IN MICE BY OPTIMAL FIXATION OF CELLS AND AVIDIN-BIOTIN COMPLEX (ABC) IMMUNOCYTOCHEMISTRY
    J GARCIAGARCIA; TAKASHIMA, I; H KARIWA; N HASHIMOTO
    JOURNAL OF IMMUNOLOGICAL METHODS, 157, 1-2, 259, 267, Jan. 1993, [Peer-reviewed]
    English, Scientific journal
  • EFFECT OF NEUTRALIZING MONOCLONAL-ANTIBODIES ON HANTAAN VIRUS-INFECTION OF THE MACROPHAGE P388D1-CELL LINE
    JS YAO; J ARIKAWA; H KARIWA; K YOSHIMATSU; TAKASHIMA, I; N HASHIMOTO
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 40, 2-3, 87, 97, Sep. 1992, [Peer-reviewed]
    English, Scientific journal
  • DEVELOPMENT AND APPLICATION OF PROTEIN-G ANTIBODY-ASSAY FOR THE DETECTION OF ANTIBODY TO HANTAVIRUS
    H KARIWA; J ARIKAWA; TAKASHIMA, I; N HASHIMOTO
    JOURNAL OF VIROLOGICAL METHODS, 37, 3, 345, 354, Jun. 1992, [Peer-reviewed]
    English, Scientific journal
  • ANTIBODY-DEPENDENT ENHANCEMENT OF HANTAVIRUS INFECTION IN MACROPHAGE CELL-LINES
    JS YAO; H KARIWA; TAKASHIMA, I; K YOSHIMATSU; J ARIKAWA; N HASHIMOTO
    ARCHIVES OF VIROLOGY, 122, 1-2, 107, 118, 1992, [Peer-reviewed]
    English, Scientific journal
  • Epidemiological research on the hemorrhagic fever with renal syndrome virus infection in brown rat.
    KARIWA HIROAKI; ARIKAWA JIRO; YO KENSHO; TAKASHIMA IKUO; HASHIMOTO NOBUO
    北海道獣医師会雑誌, 35, 3, 69, 74, Mar. 1991
    Japanese
■ Other Activities and Achievements
■ Books and other publications
  • Animal viruses
    Transworld Research Network, 2010
  • SARS
    Transworld Research Network, 2006
  • Hantaviruses and Hantavirus infections
    Times New Roman, 2003
■ 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
  • 獣医公衆衛生学特論, 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
  • 獣医公衆衛生学特論, 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
  • 人獣共通感染症対策専門特論, 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
  • 衛生学, 2024年, 学士課程, 医学部
  • 獣医公衆衛生学, 2024年, 学士課程, 獣医学部
  • 獣医疫学, 2024年, 学士課程, 獣医学部
  • アドバンスト演習, 2024年, 学士課程, 獣医学部
  • アドバンスト演習, 2024年, 学士課程, 獣医学部
  • アドバンスト演習, 2024年, 学士課程, 獣医学部
  • 畜産食品衛生学, 2024年, 学士課程, 農学部
  • 人獣共通感染症学, 2024年, 学士課程, 獣医学部
  • 獣医公衆衛生学実習, 2024年, 学士課程, 獣医学部
  • アドバンスト演習, 2024年, 学士課程, 獣医学部
■ Affiliated academic society
  • 人と動物の共通感染症研究会
  • 獣医疫学会
  • 日本ウイルス学会
  • 日本獣医学会
  • 日本獣医公衆衛生学会
  • The Japan Society of Veterinary Epidemiology
  • The Japanese Society for Virology
  • The Japanese Society of Veterinary Science
  • The Japanese Society of Veterinary Public Health
■ Research Themes
  • Development of a new serodiagnostic method for tick-borne encephalitis by immunochromatography
    Grants-in-Aid for Scientific Research
    01 Apr. 2024 - 31 Mar. 2027
    苅和 宏明; 小林 進太郎
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 24K13434
  • Development of diagnostic methods for viral zoonoses derived from wild animals and birds and the comparative epidemiological study of the viral zoonones
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2013 - 31 Mar. 2017
    KARIWA Hiroaki
    In this study, simple diagnostic methods were developed for zoonoses, such as hantavirus infections, tick-borne encephalitis, and West Nile fever, which are severe and fatal diseases, and are considered as major problems in many countries. ELISA and immunochromatography were developed to detect anti-hantavirus antibodies in various rodents. ELISA systems using viral-like particles (SPs) of tick-borne encephalitis virus conjunctive with IgG and Strep-tag were established. A stable reverse genetics system for West Nile virus was developed by using homologous recombination.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Principal investigator, Competitive research funding, 25304040
  • 近隣地域からの侵入が危惧されるわが国にない感染症の発生予防に関する研究
    厚生労働科学研究費補助金
    Apr. 2013 - Mar. 2016
    苅和 宏明
    厚生労働省, Principal investigator, Competitive research funding
  • Role of 2'-5'-oligoadenylate synthetases in the pathogenicity of flavivirus encephalitis
    Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    01 Apr. 2012 - 31 Mar. 2014
    YOSHII KENTARO; KARIWA Hiroaki
    Flaviviruses include many clinically important zoonotic pathogens, and some of them cause severe encephalitis in humans and domestic animals. In study, we showed that congenic mice expressing intact Oas1b can be applied for detailed analysis of pathogenicity of flavivirus encephalitis. Furthermore, we revealed that mutations which arose during adaptation in mammals increased the virulence of tick-borne flaviviruses.
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, 24780293
  • 海外からの侵入が危惧される野生鳥獣媒介性感染症の疫学、診断・予防法等に関する研究
    厚生労働科学研究費補助金
    Apr. 2010 - Mar. 2013
    苅和 宏明
    厚生労働省, Principal investigator, Competitive research funding
  • わが国とアメリカ大陸のウイルス性人獣共通感染症の流行阻止のための研究
    科学研究費補助金
    Apr. 2009 - Mar. 2013
    苅和 宏明
    日本学術振興会, Principal investigator, Competitive research funding
  • Study for preventing epidemic of viral zoonoses in Japan and theAmerican Continents
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2009 - 2012
    KARIWA Hiroaki; ARIKAWA Jiro; YOSHII Kentaro; MORIMATSU Kumiko
    Three novel hantaviruses were detected in Mexican rodents. The antibody detection method for various hantavirus infections was developed. Five of six monoclonal antibodies to nucleocapsid protein (NP) of Mexican hantavirus were broadly reacted with NPs of rodent-borne hantaviruses. Glycosylation of West Nile virus E protein made great influence in the pathogenesis in chicks infected with West Nile virus.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 21405035
  • Flavivirus-specific antiviral activity of 2'-5'-oligoadenylate synthetases
    Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    2010 - 2011
    YOSHII Kentaro; TAKASHIMA Ikuo; KARIWA Hiroaki; AGUI Takashi
    The interferon-inducible 2'-5'-oligoadenylate synthetases(OAS) play important roles in the antiviral activity against RNA virus infection. The murine isoform Oas1b gene has been identified as a critical determinant for genetic susceptibility to flavivirus infection. In this study, we analyzed the mechanism of the flavivirus-specific antiviral activity of Oas1b, and indicated that OAS plays crucial roles in the pathogenesis of flavivirus.
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, 22780268
  • 国内で発生のないベクター媒介性感染症の疫学診断法等の研究
    厚生労働科学研究費補助金
    Apr. 2007 - Mar. 2010
    苅和 宏明
    厚生労働省, Principal investigator, Competitive research funding
  • 日本に侵入する危険性の高い北米産ウイルス性人獣共通感染症の疫学的研究
    科学研究費補助金
    Apr. 2004 - Mar. 2008
    苅和 宏明
    日本学術振興会, Principal investigator, Competitive research funding
  • Studies on persistent hantavirus infection in rodents; throughoutanalysis of function of immune cells
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2006 - 2008
    ARIKAWA Jiro; MORIMATSU Kumiko; ENDO Rika; KARIWA Hiroaki
    ハンタウイルスは持続感染齧歯類が感染源となる人獣共通感染症でヒトに腎症候性出血熱やハンタウイルス肺症候群という重篤な疾病を引き起こす。齧歯類は血中に高い中和抗体を保有しつつ不顕性にウイルスを排泄し続けるというきわめて特徴的な持続感染を成立させている。本研究では齧歯類におけるウイルス特異的CTL抑制を中心とする免疫抑制を介したハンタウイルス持続感染成立機構の詳細を明らかにすることを目的とする。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 18300136
  • Comparalive epidemiological of study of viral zoonoses in Japan and Northern Eurasia
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    2005 - 2008
    TAKASHIMA Ikuo; KARIWA Hiroaki; MAEDA Akihiko; ARIKAWA Jiro
    近年、国内外で問題となっているウイルス性人獣共通感染症のうち、侵入または流行の危険性があり、重篤に経過し致死率が高いウエストナイル熱、ダニ媒介性脳炎およびハンタウイルス感染症について診断法を開発し、疫学調査を実施し、分離ウイルスの性状解析を行った。
    ウエストナイルウイルスと日本脳炎ウイルスの遺伝子鑑別診断法としてリアルタイムPCR法を開発した。さらに準ウイルス粒子とウイルス様粒子を用いた血清学的な鑑別診断法を開発した。極東ロシアの野鳥の中和抗体を測定したところ、91羽中15羽(16.5%)にウエストナイル特異的な中和抗体が検出されたことから、極東ロシアの野鳥間にウエストナイルウイルスの流行していることが示唆された。
    ダニ媒介性脳炎については準ウイルス粒子を用いたヒトおよび野ネズミ用の抗体検出ELISA を開発した。本ELISAを用いて国内各地の野ネズミ血清について抗体調査を実施したところ、島根県の野ネズミ58検体中2検体がダニ媒介性脳炎ウイルス特異抗体陽性となり、新しいウイルス汚染地が特定された。
    ハンタウイルス感染症では、ウイルス核タンパクを対象にしたヒトおよび野ネズミの抗体検出ELISA および抗原検出ELISAを開発した。この抗体検出ELISAを用いてタイのレプトスピラ感染症を疑われた患者に、ハンタウイルス抗体陽性例を検出したため、ハンタウイルス感染症と症状の関連が示唆された。ロシアのボルガ川流域のサマラ市において、野ネズミの疫学調査を行い、流行中のウイルスはPuumala型のハンタウイルスであることを明らかにした。北海道の中川町と当別町においてエゾヤチネズミの疫学調査を行い、ハンタウイルスの野ネズミ集団内では、オスがメスよりも有意に高い感染率を示すことを明らかにした。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 17255009
  • Epidemiological study on zoonotic diseases endemic in North America which are potentially introduced into Japan
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2004 - 2007
    KARIWA Hiroaki; TAKASHIMA Ikuo; ARIKAWA Jiro; YOSHIMATSU Kumiko
    In this study, new diagnostic methods were developed and the epidemiological surveys were carried out on West Nile fever and hantavirus infections which are potentially introduced into Japan.
    1) Development of diagnostic methods for West Nile fever: To establish the surveillance system to West Nile virus introduction to Japan, serological diagnostic methods for anti-West Nile virus antibodies were developed. The newly developed methods were the micro-neutralization test and inhibition ELISA.
    2) Epidemiological study of West Nile fever in wild birds in Far East Russia: Total RNA was extracted from kidneys of 98 birds captured in Far East Russia and West Nile virus RNA was tried to detect by RT-PCR. Although no West Nile virus RNA was detected, neutralizing antibodies to West Nile virus were detected in 15 bird sera out of 91 samples. Therefore, it is suggested that West Nile virus is circulating among wild birds in Far East Russia. Since a lot of wild birds migrate from Far East Russia to Japan, reinforcement of control measures to West Nile fever is highly required.
    3) Epidemiological study of hantavirus infections among rodents in Mexico: Virus genome detection method for hantaviruses existing in North America was developed by RT-PCR. Total RNA was extracted from lungs of 213 rodents captured in Mexico and hantavirus genome was tried to detect by RT-PCR. Among 213 samples, hantavirus RNAs were detected from 21 samples. Among these 21 virus-RNA positive rodents, 19 animals had anti-hantavirus antibodies. Therefore, it was revealed that hantaviruses are circulating among rodents in Mexico where the information of hantavirus infection is extremely limited.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 16405034
  • Structural analysis of prion proteins and mechanism of PrPsc transition by using a novel dynamic molecular structure analysis
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2005 - 2006
    INANAMI Osamu; HORIUCHI Motohiro; KARIWA Hiroaki; INABA Mustumi; KUWABARA Mikinori
    We examined the influence of D177N (178N in humans) mutation on the conformational stability of the S2 region of moPrPc with varying pHs by using the SDSL-ESR technique. We prepared moPrPc mutants that reacted with methane thiosulfonate spin-probes (Y161R1 and Y161R1/D177N). The ESR spectrum of D177N at pH 7.5 was narrower than that of Y161R1, referred to as WT^*. The ESR spectrum of D177N did not change when pH in the solution decreased from 7.5 to 4.0.These results suggested that the disappearance of a salt bridge (D177-R163) induced the increase in the instability of S2 region. The values of 1/ H of the central component (Mi=0) in the ESR spectrum obtained from WT^* remained constant from pH 7.5 to pH 6.5, whereas an abrupt increase of 1/Ho occurred when the pH in the solution decreased to under 6.0. These findings indicated that the conformational transition from a rigid structure to a flexible structure existed at between pH 6.5 and pH 6.0. Moreover, the line shape of the ESR spectrum obtained from H176S neighboring the salt bridge linked to the S2 region was narrower than that of WT^* at pH 7.5. When the pH in the solution decreased from 7.5 to 4.0, the change in the spectrum of H176S was small. These results indicate that the protonation of H 176 is strongly associated with the stability of S2 region. These findings are important for understanding the mechanism by which the disruption of the salt bridge in the S2 region forms the pathogenic PrP_Sc structure in hereditary Creutzfeldt-Jacob disease and fatal familial insomnia.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 17380178
  • 日本と極東ロシアの野生げっ歯類を病原巣動物とする人獣共通感染症の比較疫学的研究
    科学研究費補助金
    Apr. 2001 - Mar. 2004
    苅和 宏明
    日本学術振興会, Principal investigator, Competitive research funding
  • わが国のげっ歯類を病原巣動物とするウイルス性人獣共通感染症の疫学的研究
    科学研究費補助金
    Apr. 2001 - Mar. 2004
    苅和 宏明
    日本学術振興会, Principal investigator, Competitive research funding
  • Development of new defense systems in mosquito for West, Nile virus infection in Japan
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    2003 - 2004
    MIZUTANI Tetsuya; ESHITA Yuki; KARIWA Hiroaki; KURANE Ichiro
    The purpose of this research is establishment the method of controlling mosquito's growth by clarifying biological functions of JNK, and development of a new insecticide based on this fundamental research.
    The following were clarified from the research in 2003 and 2004.
    1.It was succeeded in the obstruction of growth by exposing a JNK inhibitor (SP600125) to first instar larvae of Aedes albopictus In mosquito cultured cell, JNK was confirmed to have a function of anti-apoptosis.
    2.JNK was observed the activation by adding Lipopolysaccharide(LPS) to mosquito cells, and a novel gene, which should code anti-bacterial peptide, was discovered from the cells.
    3.The transfection method of siRNA was examined for evaluating the function of JNK. Although inicroinjection siRNA against JNK to third instar larvae lead to decrease growth of mosquito, it was impossible to handle microinjection method to a lot of larvas. Then, we tried to improve the method of siRNA using reagents for transfection. However, we could not obtain superior to the microinjection method.
    4.First instar larvae was bred in the culture medium containing potent insect chitinase inhibitors of fungal origin, and the growth was obstructed by two kinds of culture medium. The gene that codes the inhibitors is now under identification.
    In this research, we clarified that JNK plays important roles in mosquito. Moreover, potent inhibitors of chitinase are useful for inhibition growth of mosquito.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), National Institute of Infectious Diseases, 15580270
  • Diagnosis, epidemiology and prevention of flavivirus infection including West Nile fever.
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    2002 - 2004
    TAKASHIMA Ikuo; KARIWA Hiroaki; MORITA Koichi; TADANO Masayuki; TAKEGAMI Tsutomu; ESHITA Yuki
    In order to prevent the outbreaks of flavivirus infections, we developed the diagnostic tests, examined pathogenecity of the viruses and examined vector susceptibility of the Japanese mosquitoes. The results are summarized as follows.
    1.Development of diagnostic tests.
    1)As the genetic diagnostic tests of West Nile virus, RT-PCR RFLP method, a real time PCR method and RT-LAMP method were developed.
    2)For tick-borne encephalitis, IgG-and IgM-ELISA using subviral particles were developed as serological diagnostic tests for human.
    2.Studies on pathogenecity of flavivirus
    1)Neuroinvasive virulence of West Nile virus New York strain was found to be associated with glysosylation of envelope protein.
    2)Neuroinvasive virulence of tick-borne encephalitis virus was reduced due to one amino acid change of envelope protein which led to the reduced vircemia.
    3.Japanese encephalitis
    1)Japanese encephalitis virus from South-East Asian countries often invaded into Japan.
    2)RNAi was found to be effective as antiviral agent to Japanese encephalitis viris.
    4.Mosquito studies
    1)Japanese indigenous mosquitoes of 4 species were found to be susceptible to West Nile virus.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 14206036
  • Development of hantavirus vaccine and rapid diagnosis kit by using soluble recombinant envelope glycoproteins
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2001 - 2003
    MORIMATSU Kumiko; ONO Eriko; MORIMATSU Masami; KARIWA Hiroaki; ARIKAWA Jiro
    1. It was clarified that recombinant Hantavirus envelope glycoproteins G1 and G2 (GPs) had the cell-fusion activity by using CAG promotor-expression system. Fusion-responsible epitope on GPs was found to locate in the neutralization (FRNT)-relating epitope. Therefore, the recombinant GPs was considered to possess neutralization-and fusion-relating epitopes. In addition, hantavirus nucleocapsid (N) protein was also expressed in mammalian cells by using same vector. As the result the N protein may suppress that expression and transportation of the envelope protein. It was also shown that the virus like particle was not formed by GPs and N protein alone.
    2. By using recombinant GPs, pseudotype vesicular stomatitis virus (VSV) enveloped with hantavirus GPs altered to VSV G protein was produced (VSVΔG*HTN). Similar pseudotype VSV was produced with recombinant GPs of Seoul virus (VSVΔG*SEO). These pseudotypes were applied to rapid neutralization assay as safety alternatives of authentic viruses. These pseudotype virus particles were also applied to vaccination as alternatives to authentic virion. Mice were immunized with soluble recombinant GPs or pseudotype virion. In mice immunized with soluble recombinant GPs, FRNT antibody was not detected. Contrary, in mice immunized with VSVΔG*HTN virion, FRNT antibody was detected. Challenge administration of hantavirus was carried out by s.c. inoculation of 4 FFU of hantavirus. These mice did not show the elevation of anti-N antibody and hantavirus specific CD8 T cell response, indicating that the FRNT antibody could protect mice from hantavirus infection. On the other hand, all control mice immunized with VSVΔG*G or PBS could not escape from hantavirus infection. These results indicated that packaged recombinant GPs on VSV particle were possible to induce protective FRNT antibody. This study shows that novel approach for the development of vaccination of viruses that have difficulties in preparation of authentic virus particles.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 13556046
  • Comparative epidemiological study on zoonotic diseases originating from wild rodents in Japan and Far East Russia
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2001 - 2003
    KARIWA Hiroaki; ARIKAWA Jiro; MIZUTANI Tetsuya; TAKASIMA Ikuo; IWASAKI Takuya
    To know the epidemiology of viral zoonotic diseases such as hemorrhagic fever with renal syndrome (HFRS) and tick-borne encephalitis (TBE) in Far East Russia, we Conducted an epizootiological survey in Khabarovsk. Anti-hantavirus antibodies were detected in Apodemus.agrarius (5/47), and Clethrionomys rufocanus (7/40) among 102 small animals captured. Partial M segments were amplified from seropositive A.agrarius. The virus nucleotide sequence in G2 region (2695-2926nt) from A agrarius had 97.0 -99.6% identities with those of FE genotypes which were identified from blood samples of HFRS patients. On the contrary, the sequence had 80.7 to 82.5% identities with those of AMR. These results suggest that hantavirus FE genotype cases severe HFRS and is carried by A agrarius. We established the ELISA to detect anti-TBE virus antibodies by using the recombinant viral E protein expressed in E.coli expression system. The ELISA could detected anti-TBE virus antibodies in C.rufocanus captured in Khabarovsk, which were also positive by authentic neutralization test. This indicate that the ELISA can be a useful method to identify the endemic areas of TBE.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 13575029
  • Epidemiological study on viral zoonotic diseases originating from wild rodents in Japan
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    2001 - 2003
    KARIWA Hiroaki; ARIKAWA Jiro; MIZUTANI Tetsuya; TAKASHIMA Ikuo; FUKUSHIMA Hiroshi; TUCHIYA Kimiyuki; ANDO Shuji
    To know the epidemiology of viral zoonotic diseases such as hemorrhagic fever with renal syndrome (HFRS) and tick-borne encephalitis (TBE) in Japan, we conducted an epizootiological survey in various points of Japan. Anti-hantavirus antibodies were detected in Apodemus. speciosus (5/482), and Clethnonomys rufocanus (7/197), Rattus norvegicus (4/364), and Rattus rattus (3/45) by Indirect fluorescent antibody assay (IFA). The positive sera from A.speciosus neutralized Hantaan virus at 1:20 but did not neutralize Seoul virus. This indicate that hantavirus carried by A.speciosus is closer to Hantaan virus than Seoul virus. The partial S gene was amplified from seropositive R.rattus and sequenced. The virus sequence had 96% identitiy with SR-11 which is Seoul virus prototype strain. These results suggest that main reservoir animals of hantavirus in Japan are A.speciosus, C. rufocanus, R.norvegicus, and R rattus.
    The rodent sera were applied to the newly established ELISA by using recombinant E protein of TBE virus to detected anti-TBE virus antibodies. The ELISA could detect anti-TBE antibodies in sera positive by neutralization test. However, no antibodies were detected in rodent sera from Toyama prefecture, in which TBE infections has not confirmed. These results suggest that the ELISA can be a useful method to identify the endemic areas of TBE in Japan.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 13660311
  • SARSコロナウイルスのウイルス粒子形成機構に関する研究
    2003
    Competitive research funding
  • Study on the mechanism of virion formation of SARS-coronavirus
    2003
    Competitive research funding
  • Differential diagnosis and vaccine development of tick-borne encephalitis
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2000 - 2002
    TAKASHIMA Ikuo; TAKAHASHI Kenichi; MIZUTANI Tetsuya; KARIWA Hiroaki; KURATA Takeshi; NEJIME Tetsuya
    We conducted epidemiological study to specify the endemic area of tick-borne encephalitis (TBE), evaluated the pathogenicity of TBE virus Hokkaido strain and tested the efficacy of European TBE vaccine to Hokkaido TBE virus strain. We also performed phylogenetic study of TBE virus Hokkaido strainsto estimate the origin.
    The results showed that TBE virus distribute in southern part of Hokkaido from the positive antibody results in dog and horse sera. Reservoir animals of TBE virus in Hokkaido were found to be Clethrionomys rufocanus and Apodemus speciosus from virus isolation results. TBE virus Hokkaido strains possessed common pathogenicity shared among TBE virus strains. TBE virus Hokkaido strain diverged from ancestor virus in Far East several hundred years ago. Another subtype of TBE virus, Siberian subtype was found to distribute in Siberian area of Russia. European type TBE virus vaccine was found to be efficacious to TBE virus Hokkaido, Far Eastern and Siberian strains. Monochlonal antibodies against TBE virus Hokkaido strain were produced and found to be useful for diagnosis.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), HOKKAIDO UNIVERSITY, 12556051
  • Pathogenesis and origin of tick-borne encephalitis virus isolated in Japan
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    1999 - 2001
    TAKASHIMA Ikuo; TAKAHASHI Kenichi; IWASAKI Takuya; KARIWA Hiroaki; MIZUTANI Tetsuya; MARUYAMA Tsutomu
    We conducted epidemiclogical study to specify the endemic area of tick-borne encephalitis (TBE), evaluated the pathogenicity of TBE virus Hokkaido strain and tested the efficacy of European TBE vaccine to Hokkaido TBE virus strain. We also performed phylogenetic study of TBE virus Hokkai strains to estimate the origin.
    The results showed that TBE virus distribute in southern part of Hokkaido from the positive antibody results in dog and horse sera. Reservoir animals of TBE virus in Hokkaido were found to Clethrionomys rufocanus and Apodemus speciosus from virus isolation result. TBE virus Hokkaido strains possessed common pathogenicity shared among TBE virus strains. TBE virus Hokkaido strain diverged from ancestor virus in Far East several hundred years ago. Another subtype of TBE virus Siberian subtype was found to distribute in Siberian area of Russia. European type TBE virus vaccine was found to be efficacious to TBE virus Hokkaido, Far Eastern and Siberian strains. Monoclonal antibodies against TBE virus Hokkaido strain were produced and found to be useful for diagnosis.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), HOKKAIDO UNIVERSITY, 11460143
  • Studies on the development of diagnosis for infectious diseases among laboratory rodents
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    1999 - 2001
    ARIKAWA Jiro; MORIMATSU Kumiko; KARIWA Hiroaki; SATO Hiroshi; TAKAKURA Akira
    1. Nucleocapsid (N) proteins of Hantaan, Seoul and Dobrava viruses were expressed by E. coli and baculovirus systems. The recombinant proteins by both systems produced enough amount of recombinant proteins and retained the anti genicity similar to those of authentic viruses. They are considered to be a ble to apply for ELISA antigen.
    2. The truncated N proteins which lacked 50 amino acids at N-terminal reduced the cross reactivity to antibody to heterologous serotypes. Therefore, the truncated antigens were applied as serotyping antigen.The ELISA with the truncated antigen able to serotype of patient and rodent sera from China and Far Eastern part of Russia as determined by ordinary neutralization test.
    3. Mouse hepatitis virus N protein gene was expressed by yeast system of which maximum expression was observed at 72 hours after culture. However, the antigenicity was too low to apply for ELISA antigen.
    4. cDNA of N protein of lymphocytic choriomeningitis (LCM) virus were cloned from Japanese isolate (strain OQ28) and prototype strain (strain WE). The cDNAs of full length, C-terminal region and central region were independently transfected to COS cells. Although they could express recombinant proteins, amount of antigen expressed was too small to apply to ELISA.
    5. Recombinant baculovirus expressing LCM virus N protein was provided from National Institute of Infectious Diseases Japan. Both the recombinant baculovirus infected SF-9 cells and Tm5 cells were found to be applicable for IFA antigen and ELISA antigen, respectively. A total of 9,840 mouse sera from 1,117 animal facility in Japan were tested for LCM virus antibody by IFA and ELISA. From these results, screening with ELISA followed by confirmation by IFA was recommended.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 11558096
  • 本邦と極東ロシアのげっ歯類におけるハンタウイルスの比較疫学的研究
    科学研究費補助金
    Apr. 1998 - Mar. 2000
    苅和 宏明
    日本学術振興会, Principal investigator, Competitive research funding
  • Molecular biologic characterization of hatavirus pathogenicity
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B).
    1999 - 2000
    ARIKAWA Jiro; MORIMATSU Kumiko; KARIWA Hiroaki; TAKASHIMA Ikuo; MORIKAWA Shigeru
    1. Epidemiologic conditions and status of vaccine development in China were investigated. Information regarding to nucleotide sequence of Chinese isolates and diagnostic procedures for serodiagnosis were exchanged.
    2. Technical information for genetic characterization of hantavirus was obtained from Slovak scientist.
    3. Technical information for characterization of hantavirus receptor and genetic reassortant virus was obtained from US scientist.
    4. Techniques for construction of artificial hantavirus was obtained from scientist of Wisconsin University School of Veterinary Medicine.
    5. Information regarding to Nephropathia epidemica virus pathogenicity was obtained from Dr.Antti Vaheri of Helsinki University.
    6. Information of epidemiologic and epizootiologic conditions in South East Asia was obtained from scientist in Thai.
    7. Infection enhancement by the GalNac specific lectin, DBA and SBA was confirmed. Involvement of cellular factor on the virus cell membrane fusion was elucidated.
    8. Pathogenicity to mice was related to growth rated at peripheral cite. The difference was considered to caused by the point mutation at enveloped protein.
    9. Viral S and M genome was cloned and expressed in the mammalian cells. Several kinds of mini-genomes were constructed for the examination of role for transcription and translation. For the next step, relationship between the minigenome expression and the proteins expressed by S and M genomes will be required.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B)., Hokkaido University, 11694228
  • Studies on a mechanism of hantavirus persistent infection in central nervous system and immune system
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A).
    1998 - 2000
    ARIKAWA Jiro; MORIKAWA Shigeru; KARIWA Hiroaki; MORIMATSU Kumiko
    1. Hantavirus infection was enhanced about 10 times by addition of lectins (DBA and SBA) which specifically bind to N-acetylgalactosamine. This enhancement was considered to caused by the cross linking between receptor to virion by the lectins.
    2. Two Vero E6 cell subclones, one induce low pH dependent cell fusion after hantavirus infection and the other resistant to cause cell fusion, were established. By using the two cell clones, the possible role for the cellular factor for responsible for induce infected cell fusion was considered.
    3. After peripheral infection of hantavirus to mice, virulent virus reached to brain 4 to 5 days earlier than that of avirulent virus. This difference was considered as a mechanism which define the virulence of hantavirus in the mouse model.
    4. Virulent hantavirus showed higher growth rate in the brain micro vascular cells and peritoneal macrophage, suggesting that virulence relates to the growth ability in the target organs.
    5. Genetic reassortant virus between virulent and avirulent viruses were established. The comparison of the virulence of the reassortant viruses indicated that one amino acid difference at enveloped protein and nucleotide difference in the polymerase gene are related to the virulence.
    6. Virulent hantavirus infected SCID mice were passively transferred with spleen cells of immunized BALB/c mice 3 weeks after infection. The recipient SCID mice represented apparent weight loss 4 days after the transfer, indicating the immune mediated pathogenicity.
    7. Hantaan virus S and M genome segment which encoding nucleocapsid protein and enveloped glycoprotein, respectively were cloned and expressed in the mammalian cells.
    8. Entire L genome segment which encodes polymerase was cloned. The expression of the L clone is under going.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A)., Hokkaido University, 10306019
  • Comparative ecological study of hantavirus in rodents in Japan and Far East Russia
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    1998 - 1999
    KARIWA Hiroaki; MIZUTANI Tetsuya; ARIKAWA Jiro; TAKASHIMA Ikuo; YOSHIMATSU Kumiko
    Epidemiological study was conducted in Japan and Far East Russia and the followings were revealed.
    1. Hantavirus was identified in the urine from infected rats. Since newborn rats intranasally inoculated with the urine containing virus had the virus in their organs and urine, the virus may be maintained by the transmission with virus-contaminated urine by intranasal route in nature.
    2. Enzyme linked immunosorbent assay (ELISA) using baculovirus-expressed nucleocapsid proteins of different hantaviruses as antigens was established. This assay made it possible to detect hantaviral antibody and also identify the type of infected hantavirus when sera were reacted with different antigens.
    3. To evaluate the virus load in patients of hantavirus pulmonary syndrome (HPS), quantitative PCR system was established. According this PCR, it was revealed that high amount of virus was detectable in blood of acute HPS patients but the virus was disappeared form blood in convalescent phase.
    4. Large scale of epidemiological study of hantavirus was conducted in Japan by using severa serological methods. In healthy adults, no one had hantaviral antibody while in hepatic disease patients of unknown etiology, 2 to 3 % of cases had the antibodies. Therefore, it is no doubt that the general public in Japan have hantavirus infections.
    5. Epizootiologic study of hantavirus targeting for rodents was carried out in Vladivostok, Far East Russia. Hantaviral antibody was detected in gray-backed vole (Clethrionomys rufocanus), hich is known to be a reservoir of Puumala type hantavirus in Hokkaido, Japan. Since stripped field mice (Apodemus agrarius), which is a reservoir of Hantaan type hantavirus in China and Korea, also had the antibodies, highly virulent strain may be prevalent in Far Eastern Russia. In addition, hantavirus genome was identified in reed vole (Microtis fortis) and sequence analysis revealed that this virus was distinct from other known hantaviruses.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), HOKKAIDO UNIVERSITY, 10660296
  • フラビウイルスの疫学的研究
    1999
    Competitive research funding
  • Epidemiological study of flaviviruses
    1999
    Competitive research funding
  • Diagnosis, prevention and epidemiology of rodent-borne zoonoses
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    1996 - 1998
    TAKASHIMA Ikuo; MARUYAMA Tsutomu; MORITA Chiharu; KANEKO Kenichi; ARIKAWA Jiro; KARIWA Hiroaki
    1) Tick-borne encephalitis ; Endemic areas of tick-borne encephalitis were distributed in 4 districs of southern Hokkaido. Two strains of tick-borne encephalitis were isolated from 600 individuals of Ixodes ovatus ticks, giving a field infection rate of 0.3% (2/600). Two strains of the virus were isolated from rodents, one from Apodemus speciosus and another from Clethrionomis rufocanus. Oshima Strain isolated previously from dog showed common neuro-invasive virulence. Vaccine in Austria was effective against Hokkaido strain of tick-borne encephalitis virus.
    2) Hantavirus infection ; Enzyme-linked immunosorbent assay was developed to diagnose the hantavirus infection for laboratory rats by using antigen generated by vaculovirus expression vector system.
    3) Q feve ; By nucleotide sequence anlysis of 16SrRNA of Coxiella burnetii Japanese isolate, they are found to be composed of one genus and one species.
    4) Other zoonoses ; Wild rodents were found to be infected with Yersinia, Salmonella and spotted fever group of Rickettia.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), HOKKAIDO UNIVERSITY, 08306018
  • Diagnosis and prevention of viral tick-borne encephalitis in Hokkaido
    Grants-in-Aid for Scientific Research
    1995 - 1997
    TAKASHIMA Ikuo; KARIWA Hiroaki
    Epidemiological investigations of tick-borne encephalitis were performed in the endemic foci where the tick-borne encephalitis patient was found and also in the other areas in Hokkaido. Results wre summarized as follows.
    1) In 1995, three strains of tick-borne enchephalitis virus were isolated from the blood of the sentinel dogs which were kept in the area where the patient was found.
    2) Two strains of tick-borne encephalitis were isolated from 600 individuals of Ixodes ovatus ticks, giving a field infection rate of 0.3% (2/600).
    3) Two strains of tick-borne encephalitis virus were isolated from rodents, one from Apodemus speciosus and another from Clethrionomis rufocanus.
    4) Virus strains isolated from dogs, ticks and rodents were identifiend as Russian Spring Summer encephalitis type of tick-borne encephalitis virus.
    5) Endemic ares of the virus were distributed in 4 districs of southern Hokkaido. These results indicate that tick-borne encephalitis virus is endemic in Hokkaido and maintained by the vector ticks Ixodes ovatus and rodents.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), HOKKAIDO UNIVERSITY, 07456138
  • わが国の野性げっ歯類におけるハンタウイルスの感染調査と新型ハンタウイルスの分離
    科学研究費補助金
    Apr. 1995 - Mar. 1996
    苅和 宏明
    日本学術振興会, Principal investigator, Competitive research funding
  • Establishment of serodiagnostic method and surveylance system for hemorrhagic fever with renal syndrome virus infection in experimental animals
    Grants-in-Aid for Scientific Research
    1994 - 1996
    ARIKAWA Jiro; TAKAKURA Akira; SUGIYAMA Kazuyoshi; YOSHIMATSU Kumiko; KARIWA Hiroaki
    1. Recombinant baculovirus expressing hantavirus nucleocapsid protein (Bac.HTN-NP) was applied for the antigen of ELISA.Specificity of the ELISA was the same to that of the IFA which uses infected Vero E6 cells as antigen. However, the ELISA had a sensitivity problem because of the relatively high background coloring.
    2. cDNA which encoded hantavirus nucleocapsid protein was expressed by using E.coli system and established capture ELISA system. This ELISA was shown to have same specificity and sensitivity to that of the ordinally IFA,and therefore, considered as a useful screening method.
    3. Bac.HTN-NP was successfully applied for the antigen for Western blotting (WB). The WB method readily distinguished specific reaction from nonspecific reaction from the WB pattern. Therefore, the WB was considered as an effective method for the serologic confirmation of hantavirus infection.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 06558112
  • Enhancement of non-specific antiviral immunity induced by mucosal administration of immunoadijivant in infant animal
    Grants-in-Aid for Scientific Research
    1994 - 1996
    ARIKAWA Jiro; TANIGUCHI Koki; KARIWA Hiroaki; KIDA Hiroshi; AZUMA Ichiro
    1. Animal models for studying respiratory infection, enteric infection and systemic infections were established by using mice and Sendai virus, rotavirus and hantavirus, respectively.
    2. MDP-Lys (L18) was selected as a immunoadjuvant and examined its effect on the enhancement of protection from infection after its administration by oral, intranasal, intrarectal and subcutaneous routes.
    3. Fatal Sendai virus infection was significantly reduced by administration of MDP-Lys (L18) through intranasal, ora and even intra rectal route.
    4. Rota virus diarrhea was significantly reduced by administration of MDP-Lys (L18) through subcutaneous, oral and intrarectal route.
    5. Fatal hantavirus infection was significantly reduced only by the administration of MDP-Lys (L18) through subcutaneous route.
    These results suggested the effect of immunoadjuvant on the augmentation of host immunity by common mucosa immune system. Further studies concerning to the quantitative estimation of the augmentation of host immunity. In addition, enhancement of specific immunity against vaccine antigen by the combination of the immunoadjuvant and mucosal administration should be studied.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 06454716
  • ハンタウイルスの生態学的研究
    1990
    Competitive research funding
  • Ecological study of hantaviruses
    1990
    Competitive research funding