研究者データベース

日尾野 隆大(ヒオノ タカヒロ)
獣医学研究院 獣医学部門 病原制御学分野
講師

基本情報

所属

  • 獣医学研究院 獣医学部門 病原制御学分野

職名

  • 講師

学位

  • 博士 (獣医学)(2015年12月 北海道大学)

科研費研究者番号

  • 00775819

J-Global ID

研究キーワード

  • レクチン   糖鎖   インフルエンザ   

研究分野

  • ライフサイエンス / 獣医学
  • ライフサイエンス / 獣医学
  • ライフサイエンス / 獣医学
  • ライフサイエンス / 機能生物化学 / 糖鎖生物学
  • ライフサイエンス / ウイルス学

職歴

  • 2021年03月 - 現在 北海道大学 大学院獣医学研究院 講師
  • 2020年04月 - 2021年02月 国立研究開発法人産業技術総合研究所 細胞分子工学研究部門 研究員
  • 2017年04月 - 2020年03月 国立研究開発法人産業技術総合研究所 創薬基盤研究部門 研究員
  • 2016年01月 - 2017年03月 北海道大学 大学院獣医学研究科 特任助教

所属学協会

  • 日本糖質学会   日本獣医学会   日本ウイルス学会   

研究活動情報

論文

  • Takahiro Hiono, Azusa Tomioka, Hiroyuki Kaji, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Atsushi Kuno
    bioRxiv 2021年04月12日 [査読無し][通常論文]
     
    AbstractThe COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2, has a global impact on public health. Since glycosylation of the viral envelope glycoproteins is known to be deeply associated with their immunogenicity, intensive studies on the glycans of its major glycoprotein, S protein, have been conducted. Nevertheless, the detailed site-specific glycan compositions of virion-associated S protein have not yet been clarified. Here, we conducted intensive glycoproteomic analyses of SARS-CoV-2 S protein using a combinatorial approach with two different technologies: mass spectrometry (MS) and lectin microarray. Using our unique MS1-based glycoproteomic technique, Glyco-RIDGE, in addition to MS2-based Byonic search, we identified 1,759 site-specific glycan compositions. The most frequent was HexNAc:Hex:Fuc:NeuAc:NeuGc = 6:6:1:0:0, suggesting a tri-antennary N-glycan terminating with LacNAc and having bisecting GlcNAc and a core fucose, which was found in 20 of 22 glycosylated sites. The subsequent lectin microarray analysis emphasized intensive outer arm fucosylation of glycans, which efficiently complemented the glycoproteomic features. The present results illustrate the high-resolution glycoproteomic features of SARS-CoV-2 S protein and significantly contribute to vaccine design, as well as the understanding of viral protein synthesis.
  • Takahiro Hiono, Atsushi Kuno
    The Analyst 145 17 5845 - 5853 2020年08月24日 
    Glycans attached to the viruses regulate their pathogenicity, immunogenicity, and antigenicity. We have previously shown that lectin microarray provided an easy and highly sensitive platform for analyzing glycan profiles of hemagglutinin (HA) of influenza A viruses in culture supernatants. On the other hand, the system is not applicable for neuraminidase (NA), the other viral glycoprotein of influenza A viruses, due to the limited availability of specific antibodies used to detect NA in the lectin microarray. Accordingly, we established replication-competent viruses harboring the short peptide-tag sequence at the C-terminus of NA in this study. The generated viruses underwent normal proliferation cycles and showed similar properties to the wild-type viruses. Lectin microarray analyses of the tagged NA enriched from the viral particles showed that glycan profiles of NA were mostly occupied by mannose-type glycans. Interestingly, the profiles were distinct from those of HA separated from the same particle preparation, in which core-fucosylated complex-type N-glycans terminating with non-sialylated N-acetyllactosamine were dominant. Collectively, this study provides novel platforms for the analyses of the distinction between the glycan profiles of NA and HA, and contributes to a better understanding of later stages of the viral life cycles through analyzing the glycans attached to NA.
  • Ankhanbaatar Ulaankhuu, Enkhbold Bazarragchaa, Masatoshi Okamatsu, Takahiro Hiono, Khishgee Bodisaikhan, Tsolmon Amartuvshin, Jargalsaikhan Tserenjav, Tsogtbaatar Urangoo, Khanui Buyantogtokh, Keita Matsuno, Takanari Hattori, Tatsunari Kondoh, Masahiro Sato, Yoshihiro Takadate, Shiho Torii, Mao Isono, Kosuke Okuya, Takeshi Saito, Nodoka Kasajima, Yurie Kida, Junki Maruyama, Manabu Igarashi, Ayato Takada, Hiroshi Kida, Damdinjav Batchuluun, Yoshihiro Sakoda
    Virus genes 56 4 472 - 479 2020年08月 [査読有り][通常論文]
     
    The circulation of highly pathogenic avian influenza viruses (HPAIVs) of various subtypes (e.g., H5N1, H5N6, H5N8, and H7N9) in poultry remains a global concern for animal and public health. Migratory waterfowls play important roles in the transmission of these viruses across countries. To monitor virus spread by wild birds, active surveillance for avian influenza in migratory waterfowl was conducted in Mongolia from 2015 to 2019. In total, 5000 fecal samples were collected from lakesides in central Mongolia, and 167 influenza A viruses were isolated. Two H5N3, four H7N3, and two H7N7 viruses were characterized in this study. The amino acid sequence at hemagglutinin (HA) cleavage site of those isolates suggested low pathogenicity in chickens. Phylogenetic analysis revealed that all H5 and H7 viruses were closely related to recent H5 and H7 low pathogenic avian influenza viruses (LPAIVs) isolated from wild birds in Asia and Europe. Antigenicity of H7Nx was similar to those of typical non-pathogenic avian influenza viruses (AIVs). While HPAIVs or A/Anhui/1/2013 (H7N9)-related LPAIVs were not detected in migratory waterfowl in Mongolia, sporadic introductions of AIVs including H5 and H7 viruses into Mongolia through the wild bird migration were identified. Thus, continued monitoring of H5 and H7 AIVs in both domestic and wild birds is needed for the early detection of HPAIVs spread into the country.
  • Yuto Kikutani, Masatoshi Okamatsu, Shoko Nishihara, Sayaka Takase-Yoden, Takahiro Hiono, Robert P de Vries, Ryan McBride, Keita Matsuno, Hiroshi Kida, Yoshihiro Sakoda
    Microbiology and immunology 2020年01月14日 [査読有り][通常論文]
     
    Avian influenza viruses (AIVs) recognize sialic acid linked α2,3 to galactose (SAα2,3Gal) glycans as receptors. In this study, the interactions between hemagglutinins (HAs) of AIVs and sulfated SAα2,3Gal glycans were analyzed to clarify the molecular basis of interspecies transmission of AIVs from ducks to chickens. It was revealed that E190V and N192D substitutions of the HA increased the recovery of viruses derived from an H6 duck virus isolate, A/duck/Hong Kong/960/1980 (H6N2), in chickens. Recombinant HAs from an H6 chicken virus, A/chicken/Tainan/V156/1999 (H6N1), bound to sulfated SAα2,3Gal glycans, whereas the HAs from an H6 duck virus did not. Binding preference of mutant HAs revealed that an E190V substitution is critical for the recognition of sulfated SAα2,3Gal glycans. These results suggest that the binding of the HA from H6 AIVs to sulfated SAα2,3Gal glycans explains a part of mechanisms of interspecies transmission of AIVs from ducks to chickens.
  • Shiho Torii, Keita Matsuno, Yongjin Qiu, Akina Mori-Kajihara, Masahiro Kajihara, Ryo Nakao, Naganori Nao, Katsunori Okazaki, Mariko Sashika, Takahiro Hiono, Masatoshi Okamatsu, Yoshihiro Sakoda, Hideki Ebihara, Ayato Takada, Hirofumi Sawa
    Ticks and tick-borne diseases 10 2 328 - 335 2019年02月 [査読有り][通常論文]
     
    Recent discoveries of tick-borne pathogens have raised public health concerns on tick-borne infectious diseases and emphasize the need to assess potential risks of unrecognized tick-borne pathogens. First, to determine the existence of tick-borne phleboviruses (TBPVs), genetic surveillance of phleboviruses in ticks was conducted mainly in Hokkaido, the northernmost island in Japan from 2013 to 2015. Genes of two TBPVs, previously reported as Mukawa virus (MKWV) and a newly identified relative of MKWV, Kuriyama virus (KURV), were detected and the viruses were isolated from Ixodes persulcatus collected in Hokkaido, but not in I. persulcatus collected from other areas of Japan. These viruses were phylogenetically and antigenically similar to each other. Next, to investigate the infection of MKWV in mammals, serum samples from wildlife captured in Hokkaido from 2007 to 2011 were used for serological screening. Neutralizing antibodies against MKWV were detected in both Yezo-deer (Cervus nippon yesoensis) (2/50) and raccoons (Procyon lotor) (16/64). However, no infectious MKWV was recovered from laboratory mice in experimental infections, though viral RNAs were detected in their tissues. Thus, MKWV and KURV may maintain tick-mammalian life cycles in Hokkaido, suggesting their potential as causative agents of tick-borne diseases in mammals.
  • Takahiro Hiono, Atsushi Matsuda, Takanori Wagatsuma, Masatoshi Okamatsu, Yoshihiro Sakoda, Atsushi Kuno
    Virology 527 132 - 140 2019年01月15日 [査読有り][通常論文]
     
    Glycan structures on hemagglutinin (HA) of influenza A viruses have been analyzed previously to understand their significance. However, the formerly established methods using mass spectrometry present disadvantages such as procedure complexity, sensitivity, and throughput. Our study has established a novel method for analyzing glycan profiles of HA using lectin microarray techniques. We successfully obtained glycan profiles of HA starting from 1 ml of the 106 TCID50 samples through simple antigen enrichment using optimized immunoprecipitation. The profiles were reasonably consistent with known glycan structures of HA. Next, we compared glycan profiles of the HAs prepared from chicken embryos, MDCK, Vero, and A549 cells, and demonstrated the host cell-specific HA glycan profiles. Notably, the HA from MDCK cells was α1-3 galactosylated. Our method provides a highly sensitive and simple procedure for glycan profiling of the viral glycoproteins, thereby paving way for direct glycan analyses of human- and animal-derived virions.
  • Zu-Jyun Wang, Yuto Kikutani, Lam Thanh Nguyen, Takahiro Hiono, Keita Matsuno, Masatoshi Okamatsu, Scott Krauss, Richard Webby, Youn-Jeong Lee, Hiroshi Kida, Yoshihiro Sakoda
    Virus genes 54 4 543 - 549 2018年08月 [査読有り][通常論文]
     
    Among 16 haemagglutinin (HA) subtypes of avian influenza viruses (AIVs), H13 AIVs have rarely been isolated in wild waterfowl. H13 AIVs cause asymptomatic infection and are maintained mainly in gull and tern populations; however, the recorded antigenic information relating to the viruses has been limited. In this study, 2 H13 AIVs, A/duck/Hokkaido/W345/2012 (H13N2) and A/duck/Hokkaido/WZ68/2012 (H13N2), isolated from the same area in the same year in our surveillance, were genetically and antigenically analyzed with 10 representative H13 strains including a prototype strain, A/gull/Maryland/704/1977 (H13N6). The HA genes of H13 AIVs were phylogenetically divided into 3 groups (I, II, and III). A/duck/Hokkaido/W345/2012 (H13N2) was genetically classified into Group III. This virus was distinct from a prototype strain, A/gull/Maryland/704/1977 (H13N6), and the virus, A/duck/Hokkaido/WZ68/2012 (H13N2), both belonging to Group I. Antigenic analysis indicated that the viruses of Group I were antigenically closely related to those of Group II, but distinct from those of Group III, including A/duck/Hokkaido/W345/2012 (H13N2). In summary, our study indicates that H13 AIVs have undergone antigenic diversification in nature.
  • A. Shibata, T. Hiono, H. Fukuhara, R. Sumiyoshi, A. Ohkawara, K. Matsuno, M. Okamatsu, H. Osaka, Y. Sakoda
    Transboundary and Emerging Diseases 65 2 465 - 475 2018年04月01日 [査読有り][通常論文]
     
    The transportation of poultry and related products for international trade contributes to transboundary pathogen spread and disease outbreaks worldwide. To prevent pathogen incursion through poultry products, many countries have regulations about animal health and poultry product quarantine. However, in Japan, animal products have been illegally introduced into the country in baggage and confiscated at the airport. Lately, the number of illegally imported poultry and the incursion risk of transboundary pathogens through poultry products have been increasing. In this study, we isolated avian influenza viruses (AIVs) from raw poultry products illegally imported to Japan by international passengers. Highly (H5N1 and H5N6) and low (H9N2 and H1N2) pathogenic AIVs were isolated from raw chicken and duck products carried by flight passengers. H5 and H9 isolates were phylogenetically closely related to viruses isolated from poultry in China, and haemagglutinin genes of H5N1 and H5N6 isolates belonged to clades 2.3.2.1c and 2.3.4.4, respectively. Experimental infections of H5 and H9 isolates in chickens and ducks demonstrated pathogenicity and tissue tropism to skeletal muscles. To prevent virus incursion by poultry products, it is important to encourage the phased cleaning based on the disease control and eradication and promote the reduction in contamination risk in animal products.
  • Mizuho Suzuki, Masatoshi Okamatsu, Yuri Fujimoto, Takahiro Hiono, Keita Matsuno, Hiroshi Kida, Yoshihiro Sakoda
    Japanese Journal of Veterinary Research 66 1 29 - 41 2018年 [査読有り][通常論文]
     
    The H10N8 influenza virus became a threat to public health when cases of fatal infections were identified in China in 2013 and 2014. Thus, genetic and antigenic characterization of H10 influenza viruses and development of an appropriate vaccine are essential to prepare for a future pandemic by H10 influenza viruses. However, current information regarding these properties of H10 influenza viruses circulating in birds is limited. In this study, genetic analysis of H10 influenza viruses revealed that the viruses recently circulating in wild birds in East Asia are genetically close to human H10N8 influenza viruses. Furthermore, the antigenicity of H10 influenza viruses was stable among the viruses circulating in birds. An inactivated vaccine was prepared from A/duck/Mongolia/245/2015 (H10N3), which is genetically and antigenically close to the human H10 influenza viruses. The vaccine induced sufficient neutralizing antibodies against homologous and heterologous viruses in mice. The inactivated vaccine induced protective immunity sufficient to reduce the impact of challenges with A/duck/Hokkaido/W87/2007 (H10N2), which is pathogenic strain in mice. This study demonstrates that the inactivated whole virus particle vaccine prepared from viruses isolated from wild birds would be useful against a future pandemic influenza by H10 influenza viruses.
  • Mizuho Suzuki, Masatoshi Okamatsu, Takahiro Hiono, Keita Matsuno, Yoshihiro Sakoda
    JOURNAL OF VETERINARY MEDICAL SCIENCE 79 11 1815 - 1821 2017年11月 [査読有り][通常論文]
     
    H2N2 influenza virus caused a pandemic starting in 1957 but has not been detected in humans since 1968. Thus, most people are immunologically naive to viruses of the H2 subtype. In contrast, H2 influenza viruses are continually isolated from wild birds, and H2N3 viruses were isolated from pigs in 2006. H2 influenza viruses could cause a pandemic if re-introduced into humans. In the present study, a vaccine against H2 influenza was prepared as an effective control measure against a future human pandemic. A/duck/Hokkaido/162/2013 (H2N1), which showed broad antigenic cross-reactivity, was selected from the candidate H2 influenza viruses recently isolated from wild birds in Asian countries. Sufficient neutralizing antibodies against homologous and heterologous viruses were induced in mice after two subcutaneous injections of the inactivated whole virus particle vaccine. The inactivated vaccine induced protective immunity sufficient to reduce the impact of challenges with A/swine/Missouri/2124514/2006 (H2N3). This study demonstrates that the inactivated whole virus particle vaccine prepared from an influenza virus library would be useful against a future H2 influenza pandemic.
  • Lam Thanh Nguyen, Tatsuya Nishi, Shintaro Shichinohe, Duc-Huy Chu, Takahiro Hiono, Keita Matsuno, Masatoshi Okamatsu, Hiroshi Kida, Yoshihiro Sakoda
    VIROLOGY 510 252 - 261 2017年10月 [査読有り][通常論文]
     
    Vaccination-primed immunity in poultry has been suggested for selection of antigenically drifted highly pathogenic avian influenza viruses (HPAIVs). In this study, we performed two consecutive passage studies of an H5N1 HPAIV in vaccinated chickens, namely, study-I and study-II, to select antigenic variants under immune pressure from the vaccination. In study-I, nine consecutive passages of a wild-type H5N1 HPAIV were carried out in chickens vaccinated with the homologous challenge strain. Antigenically drifted variants with mutations at position 179 in the hemagglutinin (HA) were selected after three passages. Similarly, in study-II, a vaccination-mediated antigenic variant isolated in study-I was used as the vaccine and challenge strain to confirm further antigenic drift after updating the vaccine; after the third passage, additional antigenic variants with a mutation at position 256 in the HA were selected. Thus, our study demonstrated the contribution of vaccination in the selection of antigenic variants of H5 HPAIVs in chickens.
  • Takahiro Hiono, Masatoshi Okamatsu, Keita Matsuno, Atsushi Haga, Ritsuko Iwata, Lam Thanh Nguyen, Mizuho Suzuki, Yuto Kikutani, Hiroshi Kida, Manabu Onuma, Yoshihiro Sakoda
    MICROBIOLOGY AND IMMUNOLOGY 61 9 387 - 397 2017年09月 [査読有り][通常論文]
     
    On 15 November 2016, a black swan that had died in a zoo in Akita prefecture, northern Japan, was strongly suspected to have highly pathogenic avian influenza (HPAI); an HPAI virus (HPAIV) belonging to the H5N6 subtype was isolated from specimens taken from the bird. After the initial report, 230 cases of HPAI caused by H5N6 viruses from wild birds, captive birds, and domestic poultry farms were reported throughout the country during the winter season. In the present study, 66 H5N6 HPAIVs isolated from northern Japan were further characterized. Phylogenetic analysis of the hemagglutinin gene showed that the H5N6 viruses isolated in northern Japan clustered into Group C of Clade 2.3.4.4 together with other isolates collected in Japan, Korea and Taiwan during the winter season of 2016-2017. The antigenicity of the Japanese H5N6 isolate differed slightly from that of HPAIVs isolated previously in Japan and China. The virus exhibited high pathogenicity and a high replication capacity in chickens, whereas virus growth was slightly lower in ducks compared with that of an H5N8 HPAIV isolate collected in Japan in 2014. Comprehensive analyses of Japanese isolates, including those from central, western, and southern Japan, as well as rapid publication of this information are essential for facilitating greater control of HPAIVs.
  • Lam Thanh Nguyen, Kazunari Nakaishi, Keiko Motojima, Ayako Ohkawara, Erina Minato, Junki Maruyama, Takahiro Hiono, Keita Matsuno, Masatoshi Okamatsu, Takashi Kimura, Ayato Takada, Hiroshi Kida, Yoshihiro Sakoda
    PLOS ONE 12 8 e0182228  2017年08月 [査読有り][通常論文]
     
    Highly pathogenic avian influenza viruses (HPAIVs) of H5 subtype have persistently caused outbreaks in domestic poultry and wild birds worldwide and sporadically infected humans. Rapid and accurate diagnosis is one of the key strategies for the control of H5 HPAIVs. However, the sensitivity of the diagnosis of H5 HPAIVs has gradually reduced due to extensive antigenic variation during their evolution. Particularly, the previously developed immunochromatographic diagnosis kit for H5 viruses, Linjudge Flu A/H5, exhibits reduced detection of H5 HPAIVs isolated in recent years. In the present study, we established a new advanced H5 rapid immunochromatographic detection kit (New Linjudge Flu A/H5) by a combination of two anti-H5 hemagglutinin monoclonal antibodies, A64/1 previously applied in the Linjudge Flu A/H5 and A32/2, a novel monoclonal antibody generated from a clade 2.3.4.4 H5 HPAIV. The new kit broadly detected all classical and recent H5 influenza viruses and showed a higher specificity and sensitivity than the original Linjudge Flu A/H5 with recently circulating H5 HPAIVs. Furthermore, the applicability of the New Linjudge Flu A/H5 was demonstrated by detecting antigens from the swabs and tissue homogenates of naturally infected birds and experimentally infected chickens with H5N6 HPAIVs belonging to the genetic clade 2.3.4.4. Our study, therefore, can provide an effective point-of-care rapid antigen detection kit for the surveillance of H5 avian influenza viruses and as a prompt countermeasure against the current widespread of the clade 2.3.4.4 H5 HPAIVs in domestic and wild birds.
  • Bazarragchaa Enkhbold, Munkhduuren Shatar, Shiho Wakamori, Tomokazu Tamura, Takahiro Hiono, Keita Matsuno, Masatoshi Okamatsu, Takashi Umemura, Batchuluun Damdinjav, Yoshihiro Sakoda
    VIRUS GENES 53 3 418 - 425 2017年06月 [査読有り][通常論文]
     
    Classical swine fever (CSF), a highly contagious viral disease affecting domestic and wild pigs in many developing countries, is now considered endemic in Mongolia, with 14 recent outbreaks in 2007, 2008, 2011, 2012, 2014, and 2015. For the first time, CSF viruses isolated from these 14 outbreaks were analyzed to assess their molecular epidemiology and pathogenicity in pigs. Based on the nucleotide sequences of their 5'-untranslated region, isolates were phylogenetically classified as either sub-genotypes 2.1b or 2.2, and the 2014 and 2015 isolates, which were classified as 2.1b, were closely related to isolates from China and Korea. In addition, at least three different viruses classified as 2.1b circulated in Mongolia. Experimental infection of the representative isolate in 2014 demonstrated moderate pathogenicity in 4-week-old pigs, with relatively mild clinical signs. Understanding the diversity of circulating CSF viruses gleans insight into disease dynamics and evolution, and may inform the design of effective CSF control strategies in Mongolia.
  • Ayako Ohkawara, Masatoshi Okamatsu, Makoto Ozawa, Duc-Huy Chu, Lam Thanh Nguyen, Takahiro Hiono, Keita Matsuno, Hiroshi Kida, Yoshihiro Sakoda
    MICROBIOLOGY AND IMMUNOLOGY 61 5 149 - 158 2017年05月 [査読有り][通常論文]
     
    H5 highly pathogenic avian influenza viruses (HPAIV) have spread in both poultry and wild birds since late 2003. Continued circulation of HPAIV in poultry in several regions of the world has led to antigenic drift. In the present study, we analyzed the antigenic properties of H5 HPAIV isolated in Asia using four neutralizing mAbs recognizing hemagglutinin, which were established using A/chicken/Kumamoto/1-7/2014 (H5N8), belonging to clade 2.3.4.4 and also using polyclonal antibodies. Viruses of clades 1.1, 2.3.2.1, 2.3.4, and 2.3.4.4 had different reactivity patterns to the panel of mAbs, thereby indicating that the antigenicity of the viruses of clade 2.3.4.4 were similar but differed from the other clades. In particular, the antigenicity of the viruses of clade 2.3.4.4 differed from those of the viruses of clades 2.3.4 and 2.3.2.1, which suggests that the recent H5 HPAIV have further evolved antigenically divergent. In addition, reactivity of antiserum suggests that the antigenicity of viruses of clade 2.3.4.4 differed slightly among groups A, B, and C. Vaccines are still used in poultry in endemic countries, so the antigenicity of H5 HPAIV should be monitored continually to facilitate control of avian influenza. The panel of mAbs established in the present study will be useful for detecting antigenic drift in the H5 viruses that emerge from the current strains.
  • Akihiro Nakatsukasa, Koji Kuruma, Masatoshi Okamatsu, Takahiro Hiono, Mizuho Suzuki, Keita Matsuno, Hiroshi Kida, Takayoshi Oyamada, Yoshihiro Sakoda
    VACCINE 35 21 2855 - 2861 2017年05月 [査読有り][通常論文]
     
    Transdermal vaccination using a microneedle (MN) confers enhanced immunity compared with subcutaneous (SC) vaccination. Here we developed a novel dissolving MN patch for the influenza vaccine. The potencies of split virion and whole virus particle (WVP) vaccines prepared from A/Puerto Rico/8/1934 (H1N1) and A/duck/Hokkaido/Vac-3/2007 (H5N1), respectively, were evaluated. MN vaccination induced higher neutralizing antibody responses than SC vaccination in mice. Moreover, MN vaccination with a lower dose of antigens conferred protective immunity against lethal challenges of influenza viruses than SC vaccination in mice. These results suggest that the WVP vaccines administered using MN are an effective combination for influenza vaccine to be further validated in humans. (C) 2017 Elsevier Ltd. All rights reserved.
  • Masatoshi Okamatsu, Makoto Ozawa, Kosuke Soda, Hiroki Takakuwa, Atsushi Haga, Takahiro Hiono, Aya Matsuu, Yuko Uchida, Ritsuko Iwata, Keita Matsuno, Masakazu Kuwahara, Toshiyo Yabuta, Tatsufumi Usui, Hiroshi Ito, Manabu Onuma, Yoshihiro Sakoda, Takehiko Saito, Koichi Otsuki, Toshihiro Ito, Hiroshi Kida
    EMERGING INFECTIOUS DISEASES 23 4 691 - 695 2017年04月 [査読有り][通常論文]
     
    Highly pathogenic avian influenza viruses (HPAIVs) A(H5N6) were concurrently introduced into several distant regions of Japan in November 2016. These viruses were classified into the genetic clade 2.3.4.4c and were genetically closely related to H5N6 HPAIVs recently isolated in South Korea and China. In addition, these HPAIVs showed further antigenic drift.
  • Taisuke Horimoto, Takahiro Hiono, Hirohisa Mekata, Tomoha Odagiri, Zhihao Lei, Tomoya Kobayashi, Junzo Norimine, Yasuo Inoshima, Hirokazu Hikono, Kenji Murakami, Reiichiro Sato, Hironobu Murakami, Masahiro Sakaguchi, Kazunori Ishii, Takaaki Ando, Kounosuke Otomaru, Makoto Ozawa, Yoshihiro Sakoda, Shin Murakami
    PLOS ONE 11 9 e0163828  2016年09月 [査読有り][通常論文]
     
    Cattle are major reservoirs of the provisionally named influenza D virus, which is potentially involved in the bovine respiratory disease complex. Here, we conducted a serological survey for the influenza D virus in Japan, using archived bovine serum samples collected during 2010-2016 from several herds of apparently healthy cattle in various regions of the country. We found sero-positive cattle across all years and in all the prefectural regions tested, with a total positivity rate of 30.5%, although the positivity rates varied among regions (13.5-50.0%). There was no significant difference in positivity rates for Holstein and Japanese Black cattle. Positivity rates tended to increase with cattle age. The herds were clearly divided into two groups: those with a high positive rate and those with a low (or no) positive rate, indicating that horizontal transmission of the virus occurs readily within a herd. These data demonstrate that bovine influenza D viruses have been in circulation for at least 5 years countrywide, emphasizing its ubiquitous distribution in the cattle population of Japan.
  • Masatoshi Okamatsu, Takahiro Hiono, Hiroshi Kida, Yoshihiro Sakoda
    VETERINARY JOURNAL 215 82 - 86 2016年09月 [査読有り][通常論文]
     
    The diagnosis of influenza A virus infections in poultry or wild birds is difficult due to variations in the pathogenicity of the viruses in different avian hosts and also the antigenic and genetic diversity of the virus, particularly the recent H5 highly pathogenic avian influenza viruses. A classical standard laboratory technique is virus isolation prior to subtyping and pathotyping. This diagnostic technique is crucial for further virological analyses, particularly during an initial outbreak; however, delays in diagnosis have thwarted effective disease control in recent years. Recent developments in molecular biological techniques provide an accelerated diagnosis. Such technologies, which include real-time reverse transcriptase PCR, isothermal nucleic acid amplification, next-generation sequencing and immunochromatography, contribute to simpler and more rapid diagnosis. The advantages of each of these diagnostic techniques should be considered for effective control of avian influenza. (C) 2016 Elsevier Ltd. All rights reserved.
  • Duc-Huy Chu, Masatoshi Okamatsu, Keita Matsuno, Takahiro Hiono, Kohei Ogasawara, Lam Thanh Nguyen, Long Van Nguyen, Tien Ngoc Nguyen, Thuy Thu Nguyen, Dong Van Pham, Dang Hoang Nguyen, Tho Dang Nguyen, Thanh Long To, Hung Van Nguyen, Hiroshi Kida, Yoshihiro Sakoda
    VETERINARY MICROBIOLOGY 192 194 - 203 2016年08月 [査読有り][通常論文]
     
    A total of 3,045 environmental samples and oropharyngeal and cloacal swabs from apparently healthy poultry have been collected at three live bird markets (LBMs) at which practices were applied to reduce avian influenza (AI) virus transmission (intervention LBMs) and six conventional LBMs (non-intervention LBMs) in Thua Thien Hue province in 2014 to evaluate the efficacy of the intervention LBMs. The 178 AI viruses, including H3 (19 viruses), H4 (2), H5 (8), H6 (30), H9 (114), and H11 (5), were isolated from domestic ducks, muscovy ducks, chickens, and the environment. The prevalence of AI viruses in intervention LBMs (6.1%; 95% CI: 5.0-7.5) was similar to that in non-intervention LBMs (5.6%; 95% CI: 4.5-6.8; x(2) = 0.532; df = 1; P = 0.53) in the study area. Eight H5N6 highly pathogenic avian influenza (HPAI) viruses were isolated from apparently healthy ducks, muscovy ducks, and an environmental sample in an intervention LBM. The hemagglutinin genes of the H5N6 HPAI viruses belonged to the genetic Glade 23.4.4, and the antigenicity of the H5N6 HPAI viruses differed from the H5N1 HPAI viruses previously circulating in Vietnam. Phylogenetic and antigenic analyses of the H6 and H9 viruses isolated in both types of LBMs revealed that they were closely related to the viruses isolated from domestic birds in China, Group II of H6 viruses and Y280 lineage of H9 viruses. These results indicate that the interventions currently applied in LBMs are insufficient to control AI. A risk analysis should be conducted to identify the key factors contributing to Al virus prevalence in intervention LBMs. (C) 2016 Elsevier B.V. All rights reserved.
  • Masatoshi Okamatsu, Yurie Motohashi, Takahiro Hiono, Tomokazu Tamura, Kazuki Nagaya, Keita Matsuno, Yoshihiro Sakoda, Hiroshi Kida
    ARCHIVES OF VIROLOGY 161 8 2235 - 2242 2016年08月 [査読有り][通常論文]
     
    Influenza viruses isolated from wild ducks do not replicate in chickens. This fact is not explained solely by the receptor specificity of the hemagglutinin (HA) from such viruses for target host cells. To investigate this restriction in host range, the fusion activities of HA molecules from duck and chicken influenza viruses were examined. Influenza viruses A/duck/Mongolia/54/2001 (H5N2) (Dk/MNG) and A/chicken/Ibaraki/1/2005 (H5N2) (Ck/IBR), which replicate only in their primary hosts, were used. The optimal pH for membrane fusion of Ck/IBR was 5.9, higher than that of Dk/MNG at 4.9. To assess the relationship between the optimal pH for fusion and the host range of avian influenza viruses, the optimal pH for fusion of 55 influenza virus strains isolated from ducks and chickens was examined. No correlation was found between the host range and optimal pH for membrane fusion by the viruses, and this finding applied also to the H5N1 highly pathogenic avian influenza viruses. The optimal pH for membrane fusion for avian influenza viruses was shown to not necessarily be correlated with their host range or pathogenicity in ducks and chickens.
  • Hiromi Takaki, Haruko Sato, Riho Kurata, Hirokazu Hikono, Takahiro Hiono, Hiroshi Kida, Misako Matsumoto, Takehiko Saito, Tsukasa Seya
    Microbiology and immunology 60 7 511 - 5 2016年07月 [査読有り][通常論文]
     
    Eye spray influenza vaccines for chickens are increasingly available; however, how to enhance cellular and antibody responses to them remains undetermined. Here, eye-drops containing the immune-enhancing adjuvants Pam2CSK4 or polyI:C were assessed in chickens. Application of these TLR agonists to chicken conjunctiva resulted in up-regulation of IL-1β, but not other cytokines, including IFN and IL-6, in the spleen, lung and Harderian gland. Thus, responses to adjuvant applied to the conjunctival mucosa of chickens differ from those expected from the responses to intra-nasal adjuvants in mammals. Identifying an appropriate delivery route for adjuvants is crucial for evoking immune responses in chickens.
  • Takahiro Hiono, Masatoshi Okamatsu, Manabu Igarashi, Ryan McBride, Robert P. de Vries, Wenjie Peng, James C. Paulson, Yoshihiro Sakoda, Hiroshi Kida
    ARCHIVES OF VIROLOGY 161 2 307 - 316 2016年02月 [査読有り][通常論文]
     
    Influenza viruses isolated from ducks are rarely able to infect chickens; it is therefore postulated that these viruses need to adapt in some way to be able to be transmitted to chickens in nature. Previous studies revealed that sialyl Lewis X (3'SLeX), which is fucosylated alpha 2,3 sialoside, was predominantly detected on the epithelial cells of the chicken trachea, whereas this glycan structure is not found in the duck intestinal tract. To clarify the mechanisms of the interspecies transmission of influenza viruses between ducks and chickens, we compared the receptor specificity of low-pathogenic avian influenza viruses isolated from these two species. Glycan-binding analysis of the recombinant hemagglutinin (HA) of a chicken influenza virus, A/chicken/Ibaraki/1/2005 (H5N2), revealed a binding preference to alpha 1,3 fucosylated sialosides. On the other hand, the HA of a duck influenza virus, A/duck/Mongolia/54/2001 (H5N2) (Dk/MNG), particularly bound to non-fucosylated alpha 2,3 sialosides such as 3'-sialyllactosamine (3'SLacNAc). Computational analysis along with binding analysis of the mutant HAs revealed that this glycan-binding specificity of the HA was determined by amino acid residues at positions 222 and 227. Inconsistent with the glycan-binding specificity of the recombinant HA protein, virions of Dk/MNG bound to both 3'SLacNAc and 3'SLeX. Glycan-binding analysis in the presence of a neuraminidase (NA) inhibitor revealed that the NA conferred binding to 3'SLeX to virions of Dk/MNG. The present results reveal the molecular basis of the interaction between fucosylated alpha 2,3 sialosides and influenza viruses.
  • Takahiro Hiono, Keita Matsuno, Kotaro Tuchiya, Zhifeng Lin, Masatoshi Okamatsu, Yoshihiro Sakoda
    Genome Announcements 4 5 2016年 [査読有り][通常論文]
     
    Here, we report the complete genome sequence of the avian paramyxovirus serotype 5 strain APMV-5/budgerigar/Japan/TI/75, which was determined using the Illumina MiSeq platform. The determined sequence shares 97% homology and similar genetic features with the previously known genome sequence of avian paramyxovirus serotype 5 strain APMV-5/budgerigar/Japan/Kunitachi/74.
  • Takahiro Hiono, Masatoshi Okamatsu, Naoki Yamamoto, Kohei Ogasawara, Mayumi Endo, Saya Kuribayashi, Shintaro Shichinohe, Yurie Motohashi, Duc-Huy Chu, Mizuho Suzuki, Takaya Ichikawa, Tatsuya Nishi, Yuri Abe, Keita Matsuno, Kazuyuki Tanaka, Tsutomu Tanigawa, Hiroshi Kida, Yoshihiro Sakoda
    VETERINARY MICROBIOLOGY 182 108 - 115 2016年01月 [査読有り][通常論文]
     
    Highly pathogenic avian influenza viruses (HPAIVs) have spread in both poultry and wild birds. Determining transmission routes of these viruses during an outbreak is essential for the control of avian influenza. It has been widely postulated that migratory ducks play crucial roles in the widespread dissemination of HPAIVs in poultry by carrying viruses along with their migrations; however close contacts between wild migratory ducks and poultry are less likely in modern industrial poultry farming settings. Therefore, we conducted experimental infections of HPAIVs and low pathogenic avian influenza viruses (LPAIVs) to chickens, domestic ducks, tree sparrows, jungle crows, and black rats to evaluate their roles in virus transmission. The results showed that chickens, ducks, sparrows, and crows were highly susceptible to HPAIV infection. Significant titers of virus were recovered from the sparrows and crows infected with HPAIVs, which suggests that they potentially play roles of transmission of HPAIVs to poultry. In contrast, the growth of LPAIVs was limited in each of the animals tested compared with that of HPAIVs. The present results indicate that these common synanthropes play some roles in influenza virus transmission from wild birds to poultry. (C) 2015 Elsevier B.V. All rights reserved.
  • Takahiro Hiono, Ayako Ohkawara, Kohei Ogasawara, Masatoshi Okamatsu, Tomokazu Tamura, Duc-Huy Chu, Mizuho Suzuki, Saya Kuribayashi, Shintaro Shichinohe, Ayato Takada, Hirohito Ogawa, Reiko Yoshida, Hiroko Miyamoto, Naganori Nao, Wakako Furuyama, Junki Maruyama, Nao Eguchi, Gerelmaa Ulziibat, Bazarragchaa Enkhbold, Munkhduuren Shatar, Tserenjav Jargalsaikhan, Selenge Byambadorj, Batchuluun Damdinjav, Yoshihiro Sakoda, Hiroshi Kida
    VIRUS GENES 51 1 57 - 68 2015年08月 [査読有り][通常論文]
     
    Migratory water birds are the natural reservoir of influenza A viruses. H5 and H7 influenza viruses are isolated over the world and also circulate among poultry in Asia. In 2010, two H5N1 highly pathogenic avian influenza viruses (HPAIVs) were isolated from fecal samples of water birds on the flyway of migration from Siberia, Russia to the south in Hokkaido, Japan. H7N9 viruses are sporadically isolated from humans and circulate in poultry in China. To monitor whether these viruses have spread in the wild bird population, we conducted virological surveillance of avian influenza in migratory water birds in autumn from 2010 to 2014. A total of 8103 fecal samples from migratory water birds were collected in Japan and Mongolia, and 350 influenza viruses including 13 H5 and 19 H7 influenza viruses were isolated. A phylogenetic analysis revealed that all isolates are genetically closely related to viruses circulating among wild water birds. The results of the antigenic analysis indicated that the antigenicity of viruses in wild water birds is highly stable despite their nucleotide sequence diversity but is distinct from that of HPAIVs recently isolated in Asia. The present results suggest that HPAIVs and Chinese H7N9 viruses were not predominantly circulating in migratory water birds; however, continued monitoring of H5 and H7 influenza viruses both in domestic and wild birds is recommended for the control of avian influenza.
  • Duc-Huy Chu, Yoshihiro Sakoda, Tatsuya Nishi, Takahiro Hiono, Shintaro Shichinohe, Masatoshi Okamatsu, Hiroshi Kida
    VACCINE 32 28 3473 - 3479 2014年06月 [査読有り][通常論文]
     
    H7N9 influenza virus infection in humans was reported in China on March 31, 2013. Humans are immunologically naive to the H7N9 subtype, for which the seasonal influenza vaccine is not effective. Thus, the development of an H7N9 influenza virus vaccine is an urgent issue. To prepare for the emergence of an influenza pandemic, we have established a library comprising more than 1300 influenza virus strains with 144 different combinations of 16 HA and 9 NA subtypes. An H7N9 virus strain isolated from a 35-year-old woman, A/Anhui/1/2013 (H7N9), was found to be antigenically similar to H7N9 influenza viruses isolated from migratory ducks. In the present study, the potency of an inactivated whole virus particle vaccine prepared from an H7N9 low pathogenic avian influenza virus, A/duck/Mongolia/119/2008 (H7N9), selected from the library, was assessed by a challenge with A/Anhui/1/2013 (H7N9). The results indicate that the test vaccine was potent enough to induce sufficient immunity to reduce the impact of disease caused by the challenge with A/Anhui/1/2013 (H7N9) in mice. The present results indicate that an inactivated whole virus particle vaccine prepared from an influenza virus strain stored in the library could be useful as a vaccine strain in case of an influenza pandemic. (C) 2014 Published by Elsevier Ltd.
  • Yasushi Itoh, Reiko Yoshida, Shintaro Shichinohe, Megumi Higuchi, Hirohito Ishigaki, Misako Nakayama, Van Loi Pham, Hideaki Ishida, Mitsutaka Kitano, Masahiko Arikata, Naoko Kitagawa, Yachiyo Mitsuishi, Kazumasa Ogasawara, Hideaki Tsuchiya, Takahiro Hiono, Masatoshi Okamatsu, Yoshihiro Sakoda, Hiroshi Kida, Mutsumi Ito, Le Quynh Mai, Yoshihiro Kawaoka, Hiroko Miyamoto, Mari Ishijima, Manabu Igarashi, Yasuhiko Suzuki, Ayato Takada
    PLOS PATHOGENS 10 6 e1004192  2014年06月 [査読有り][通常論文]
     
    Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.
  • Hiono T, Okamatsu M, Nishihara S, Takase-Yoden S, Sakoda Y, Kida H
    Virology 456 131 - 138 2014年05月 [査読有り][通常論文]
     
    Influenza viruses recognize sialoglycans as receptors. Although viruses isolated form chickens preferentially bind to sialic acid alpha 2,3 galactose (SA alpha 2,3Gal) glycans as do those of ducks, chickens were not experimentally infected with viruses isolated from ducks. A chicken influenza virus, A/chicken/Ibaraki/1/ 2005 (H5N2) (Ck/IBR) bound to fucose-branched SAa2,3Gal glycans, whereas the binding towards linear SAa2,3Gal glycans was weak. On the epithelial cells of the upper respiratory tracts of chickens, fucose-branched SA alpha 2,3Gal glycans were detected, but not linear SA alpha 2,3Gal glycans. The growth of Ck/IBR in MDCK-FUT cells, which were genetically prepared to express fucose-branched SA alpha 2,3Gal glycans, was significantly higher than that in the parental MDCK cells. The present results indicate that fucosebranched SA alpha 2,3Gal glycans existing on the epithelial cells lining the upper respiratory tracts of chickens are critical for recognition by Ck/IBR. (c) 2014 Elsevier Inc. All rights reserved.
  • Masatoshi Okamatsu, Yoshihiro Sakoda, Takahiro Hiono, Naoki Yamamoto, Hiroshi Kida
    VIROLOGY JOURNAL 10 47  2013年02月 [査読有り][通常論文]
     
    Background: The pandemic 2009 (H1N1) influenza virus has spread throughout the world and is now causing seasonal influenza. To prepare for the emergence of pandemic influenza, we have established a library of virus strains isolated from birds, pigs, and humans in global surveillance studies. Methods: Inactivated whole virus particle (WV) and ether-split (ES) vaccines were prepared from an influenza virus strain, A/swine/Hokkaido/2/1981 (H1N1), from the library and from A/Narita/1/2009 (H1N1) pandemic strain. Each of the vaccines was injected subcutaneously into mice and their potencies were evaluated by challenge with A/Narita/1/2009 (H1N1) virus strain in mice. Results: A/swine/Hokkaido/2/81 (H1N1), which was isolated from the lung of a diseased piglet, was selected on the basis of their antigenicity and growth capacity in embryonated chicken eggs. Two injections of the WV vaccine induced an immune response in mice, decreasing the impact of disease caused by the challenge with A/Narita/1/2009 (H1N1), as did the vaccine prepared from the homologous strain. Conclusion: The WV vaccine prepared from an influenza virus in the library is useful as an emergency vaccine in the early phase of pandemic influenza.

その他活動・業績

受賞

  • 2019年09月 日本獣医学会 獣医学奨励賞
     鳥インフルエンザウイルスの異種宿主間伝播機構解明に向けたヘマグルチニン分子の糖質科学的解析
  • 2015年04月 9th International Symposium on Avian Influenza Student Poster Award
     
    受賞者: 日尾野隆大
  • 2013年03月 日本獣医学会微生物分科会 第4回若手奨励賞
     
    受賞者: 日尾野隆大

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