迫田 義博 (サコダ ヨシヒロ)

獣医学研究院 獣医学部門 病原制御学分野教授
人獣共通感染症国際共同研究所教授
教育イノベーション機構教授
総合イノベーション創発機構ワクチン研究開発拠点教授
One Healthリサーチセンター教授

研究者基本情報

■ 学位
  • 博士(獣医学), 北海道大学
■ URL
researchmap URLホームページURL■ ID 各種
研究者番号
  • 40333637
J-Global ID■ 研究キーワード・分野
研究分野
  • ライフサイエンス, 獣医学, 微生物学
  • ライフサイエンス, ウイルス学
■ 担当教育組織

経歴

■ 経歴
経歴
  • 2025年04月 - 現在
    北海道大学, 大学院獣医学研究院長、学部長
  • 2014年04月 - 現在
    北海道大学, 大学院獣医学研究院, 教授
  • 2005年 - 2014年03月
    北海道大学, 大学院獣医学研究科, 准教授
  • 2001年 - 2005年
    北海道大学, 大学院獣医学研究科, 助教
学歴
  • 1994年, 北海道大学, 獣医学部, 獣医, 日本国
  • 1994年, 北海道大学, Faculty of Veterinary Medicine
委員歴
  • 2018年10月 - 現在
    国際獣疫事務局(OIE)高病原性鳥インフルエンザレファレンスラボラトリー, 責任者, その他
  • 2008年 - 現在
    環境省鳥インフルエンザ等野鳥対策に係る専門家グループ会合 委員, 政府
  • 2013年 - 2014年
    家禽疾病小委員会委員, 政府
  • 2007年 - 2009年
    鳥インフルエンザパンフレット作成委員会 座長, 学協会
学内役職歴
  • 教育研究評議会評議員, 2021年4月1日 - 2023年3月31日
  • 教育研究評議会評議員, 2023年4月1日 - 2025年3月31日
  • 大学院獣医学研究院副研究院長, 2021年4月1日 - 2023年3月31日
  • 大学院獣医学研究院副研究院長, 2023年4月1日 - 2025年3月31日

研究活動情報

■ 受賞
  • 2016年, 北海道大学, 北海道大学研究総長賞
    迫田 義博
  • 2014年, 北海道大学, 北海道大学研究総長賞
    迫田 義博
  • 2013年03月, 日本獣医学会, 日本獣医学会賞
    「ペスチウイルスの分子疫学と病原性に関する研究」
    迫田 義博
  • 2008年, 若手農林水産研究者表彰
    「高病原性鳥インフルエンザの診断と予防法の開発に関する研究」
    迫田 義博
  • 2006年, アジア獣医系大学協会, アジア獣医系大学協会賞
    「高病原性鳥インフルエンザの疫学と病原性に関する研究」
    迫田 義博
■ 論文
  • Length and density of α2-3 sialyllactose-containing chains on glycopolymers determine receptor binding of avian influenza viruses
    Daiki Kobayashi; Takahiro Hiono; Ryota Adachi; Manabu Igarashi; Takahiko Matsushita; Norikazu Isoda; Yoshihiro Sakoda; Koji Matsuoka
    Archives of Virology, 171, 3, Springer Science and Business Media LLC, 2026年02月26日
    研究論文(学術雑誌)
  • Neuraminidase of influenza A viruses induces global desialylation of host cells via its intracellular function.
    Daiki Kobayashi; Takahiro Hiono; Norikazu Isoda; Yoshihiro Sakoda
    Microbiology spectrum, e0332825, 2026年02月18日, [国際誌]
    英語, 研究論文(学術雑誌), The neuraminidase protein (NA) of influenza A viruses (IAVs) plays a role in the release of viruses from infected cells. NA on viral particles hydrolyzes sialylated glycans on the cell surface for viral budding. However, the maturation and intracellular functions of NA are poorly understood. To investigate how NA functions intracellularly, glycans displayed on IAV-infected cells were profiled by lectins, and global glycome alterations, accompanied by exposed terminal galactose and glycan recapping with α1-2 fucose, were found in the virus-infected cells. Since α1-2 fucosyltransferases are localized in the Golgi, these unique structures suggest a potential NA function in the IAV-infected cells. Functional analyses using antivirals and NA-expressing cells indicate that intracellular NA function is necessary for the glycome alterations. Time-course analyses in IAV-infected cells revealed that global desialylation and α1-2 fucosylation could be observed 5 h post-inoculation, corresponding to the timeframe of viral protein expression. These observations provide a novel theory of NA functions that NA obtains its enzymatic activity intracellularly before virus assembly and serves desialylated glycans for competitive glycosyltransferases, including α1-2 fucosyltransferases, as their acceptors, resulting in glycan recapping with α1-2 fucose. Hence, intracellular NA blocks the re-sialylation of glycans, promoting efficient virus release from infected cells by inhibiting the interaction between progeny virions and sialosides. This study further demonstrated the potential NA functions of limiting secondary IAV infection. These findings provide insights into the evolutionary strategies of IAVs for shaping the strict window of superinfection by NA functions under a balance between successful replication and reassortment.IMPORTANCEInfluenza A viruses (IAVs) exploit glycans for their replication cycle. The hemagglutinin protein uses sialic acid for viral attachment, and the neuraminidase protein (NA) hydrolyzes sialosides for virus release. However, the intracellular functions of NA are not well understood. This study demonstrated that intracellular NA induces global desialylation and glycan recapping with unique structures in IAV-infected cells. This suggests a novel mode of NA function during the IAV lifecycle, where virus particles are ready to be released at the assembly, and NAs no longer need to hydrolyze the sialic acids upon egress from the cells. Therefore, the present study provides novel and significant insights into the fundamental understanding of the lifecycle of IAV. Furthermore, as NA is a primary target for anti-influenza drugs, understanding the mechanism of intracellular NA function may also support the development of antivirals.
  • Comparative evaluation of commercial enzyme-linked immunosorbent assay kits for antibody monitoring of classical swine fever virus in Japanese pig herds: performance assessment of domestic and foreign kits.
    Miki Koyasu; Keisuke Kuwata; Shuko Inoha; Yoko Kimura; Kaoru Hatate; Daiki Kobayashi; Takahiro Hiono; Norikazu Isoda; Yoshihiro Sakoda
    The Journal of veterinary medical science, 88, 2, 347, 354, 2026年02月01日, [国内誌]
    英語, 研究論文(学術雑誌), Classical swine fever (CSF) is a highly contagious disease in pigs, and vaccination with antibody monitoring is critical for its prevention. In this study, the effectiveness of two enzyme-linked immunosorbent assay (ELISA) kits for antibody detection against CSF virus (CSFV)-an indirect ELISA kit authorized in Japan in 2001 (N-kit) and a competitive ELISA kit additionally authorized in 2024 (I-kit)-was compared. For each ELISA kit, detection accuracy in terms of sensitivity, specificity and agreement rate, and quantitative accuracy were evaluated based on neutralizing antibody titers determined by serum neutralization tests. In addition, the impact of serum heat-inactivation at 56°C for 30 min on ELISA results was assessed. The results indicated that the I-kit showed the highest sensitivity and agreement rate in detection accuracy, whereas the N-kit showed the highest quantitative accuracy. Although blocking rates of the I-kit increased after heat-inactivation, high correlation rates between treated and untreated samples were confirmed for both kits, suggesting that heat-inactivation does not affect the final interpretation of the test results. These findings demonstrated that the I-kit is suitable for initial antibody screening in pigs due to its higher sensitivity, whereas the N-kit provides better quantitative accuracy, making it preferable for measuring antibody titers in sows. Therefore, the selection of an appropriate ELISA kit according to the purpose of antibody detection is necessary to ensure a more accurate evaluation of the effects of CSFV vaccination on preventing CSF in pig herds.
  • Evaluation of the Efficacy of Low-Concentration Gaseous Chlorine Dioxide in Inactivating Airborne H5 High Pathogenicity Avian Influenza Virus in Vivo Model.
    Yik Lim Hew; Norikazu Isoda; Takanori Miura; Takahiro Hiono; Yoshihiro Sakoda
    Food and environmental virology, 18, 1, 4, 4, 2026年01月23日, [国際誌]
    英語, 研究論文(学術雑誌), H5 high pathogenicity avian influenza virus (HPAIV) continues to spread globally, causing several high pathogenicity avian influenza (HPAI) outbreaks in poultry and significant economic losses. Biosecurity measures that prevent the introduction of HPAIV represent a top priority for controlling HPAI outbreaks on poultry farms. Although these measures are crucial for minimizing HPAI introduction, outbreaks of viral infection on poultry farms persist, underscoring the importance of continuously improving biosecurity protocols. Therefore, safe and effective microbicide disinfectants could play an essential role in reducing viral spread by inactivating viral particles on surfaces and in the air. This study assessed the efficacy of gaseous chlorine dioxide (ClO2) against H5 HPAIV under both gaseous ClO2 inactivation setting and in vivo conditions. In the gaseous ClO2 inactivation setting, only low virus titers were recovered (< 0.5-1.5 log10 TCID50/mL) when H5 HPAIV aerosols were exposed to gaseous ClO2 (0.05 ppmv, 0.14 mg/m3) for 5 min, corresponding to an approximately 2.0-3.0 log10 reduction. Furthermore, in vivo, all chicks exposed to aerosolized H5 HPAIV, which were treated with 0.1 ppmv gaseous ClO2, survived for 14 days post-challenge, demonstrating complete protection against the virus. The minimum effective concentration of gaseous ClO2 was 0.01 ppmv for 5 min of inactivation in the inactivation setting, and 0.05 ppmv for 5 min in vivo, indicating that relatively low concentrations are sufficient for effective viral inactivation. Therefore, gaseous ClO2 was effective at inactivating aerosolized H5 HPAIV and has potential for use as a disinfectant to prevent HPAIV introduction into poultry. (245/250) words.
  • Characterization of H5N1 high pathogenicity avian influenza virus belonging to clade 2.3.4.4b isolated from Ezo red fox in Japan in a mouse model.
    Shintaro Shichinohe; Takahiro Hiono; Yasushi Itoh; Kosuke Takada; Yurie Kida; Pei Wang; Daisuke Motooka; Norikazu Isoda; Ayato Takada; Yoshihiro Sakoda; Tokiko Watanabe
    Microbiology spectrum, 14, 1, e0109725, 2026年01月06日, [国際誌]
    英語, 研究論文(学術雑誌), H5N1 high pathogenicity avian influenza virus (HPAIV) has spread in wild birds and poultry worldwide. H5N1 HPAIV belonging to the currently predominant clade 2.3.4.4b has infected not only birds but also mammals (wild and domestic animals), with several human infections also being reported, raising concerns for public health. In 2022, a clade 2.3.4.4b H5N1 HPAIV strain, A/Ezo red fox/Hokkaido/1/2022 (H5N1; Fox/Hok/1/22), was isolated from an Ezo red fox (Vulpes vulpes schrencki) in Hokkaido, Japan; this was the first reported case of clade 2.3.4.4b H5N1 HPAIV isolation from a mammalian species in Japan. Several amino acid substitutions in the PB2 protein play an important role in the adaptation of avian influenza viruses to mammals, but Fox/Hok/1/22 PB2 does not have any of these well-known mammalian-adapting PB2 substitutions. Here, we investigated the biological properties of Fox/Hok/1/22 in a mouse model and found that this virus was highly virulent in mice and replicated well in multiple organs, including the lungs and brain. We then examined whether viruses isolated from these organs acquired known mammalian-adapting PB2 amino acid substitutions, such as PB2 E627K. Deep sequencing analysis of viral RNA from mouse brain and lungs revealed that virus with PB2-627E was predominant in three of four mice, whereas the PB2-627K substitution was predominant in one mouse. These results indicate that Fox/Hok/1/22 is highly virulent in mice despite lacking known PB2 substitutions involved in mammalian adaptation.IMPORTANCEThe H5N1 avian influenza virus has caused severe disease in birds worldwide and is now spreading to mammals, including humans. In 2022, this virus was detected for the first time in an Ezo red fox in Japan. To understand its potential impact on mammals, we studied this virus in mice and found that it caused severe illness, spreading to multiple organs, including the lungs and brain. Surprisingly, despite lacking genetic mutations typically associated with mammalian adaptation, the virus was highly virulent in mice. This finding suggests that the H5N1 virus may pose a greater threat to mammals, including humans, than previously thought. Given their continued spread among wild and domestic animals, our findings underscore the urgent need to monitor how recent H5N1 viruses behave in mammals.
  • Introduction and inter-species transmission dynamics of high pathogenicity avian influenza H5N1 viruses in Japan 2021-25.
    Yik Lim Hew; Claire Guinat; Manon Couty; Diletta Fornasiero; Takahiro Hiono; Norikazu Isoda; Yoshihiro Sakoda
    Virus evolution, 12, 1, veag005, 2026年, [国際誌]
    英語, 研究論文(学術雑誌), High pathogenicity avian influenza virus impacts poultry and wild birds worldwide. Since the introduction of clade 2.3.4.4b H5N1 isolates in Japan in late 2021, new cases have been reported in domestic birds and poultry each winter. To understand the role of wild birds in introducing these viruses in Japan, a phylodynamic analysis based on geography and host species was conducted using H5N1 isolates in Japan from 2021 to 2025. A total of 892 hemagglutinin gene sequences of H5N1 viruses, collected from birds between June 2021 and May 2025, along with additional sequences that were highly similar to those of Japanese isolates, were obtained from a public database. The role of wild birds in the transmission dynamics of H5N1 isolates in Japan across four winter seasons (2021-25) was assessed using a Bayesian phylodynamic approach with a Multi-Type Birth-Death model. Phylodynamic analysis revealed that the clade 2.3.4.4b comprised three distinct subgroups, G2b, G2c, and G2d, which were prevalent during the winter seasons. Isolates from G2b and G2c were linked to common ancestral strains from North Asia and Northeast Asia, respectively. Meanwhile, G2d, the dominant strain in Japan from 2021 to 2025, shared an ancestral strain from the Northwest America. During winters 2023-25, the ancestral strain was traced back to Northeast Asia, indicating a shift in the viral origin. This transition suggests an increase in virus migration events and expansion of host diversity, implying that Japan may function as a hub for intercontinental virus introductions, receiving multiple independent viral entries from North Asia, Northeast Asia, and Northwest America. Additionally, waterfowl and raptors played a role in introducing viruses into Japan, while poultry and crows generally serving as dead-end hosts. However, the continuous introduction of H5N1 isolates into Japan each winter can alter the disease transmission pattern observed in crows, resulting in more virus spillover from crows to other hosts, such as poultry and charadriiformes. These findings emphasize the importance of continuous monitoring and prompt information sharing to understand the global dynamics of viruses better.
  • Risk analysis of infectious disease in pigs in Gifu prefecture, Japan, through network analysis.
    Naotoshi Kuninaga; Emi Yoshita; Miki Koyasu; Hibiki Morimoto; Noboru Hayashi; Takahiro Hiono; Satoshi Ito; Yoshihiro Sakoda; Norikazu Isoda
    Preventive veterinary medicine, 245, 106687, 106687, 2025年12月, [国際誌]
    英語, 研究論文(学術雑誌), Movements of livestock, humans, vehicles and wildlife are recognized as critical contributors to the spread of infectious diseases in livestock and can be modeled as a network to assess and predict disease transmission. This study developed a comprehensive multilayer network incorporating the movements of pigs, humans, vehicles, and, presumably, wild boars to estimate the risks of disease introduction and transmission for each husbandry stakeholder and to identify key clusters and modes of movement involved. A questionnaire-based study was conducted across 22 pig farms in Gifu Prefecture, Japan, collecting data on pig, human, and vehicle movements to establish networks. The wild boar movement network was estimated using data on pig farm locations and wild boar habitats collected from vegetation cover data. Movement-associated effects in each network based on movement frequency were assigned to combinations of the four networks, resulting in a four-layered network. The network exhibited small-world characteristics and was clustered into four groups. Disease containment schemes in livestock are commonly established along administrative boundaries, however these four epidemiological clusters, comprising 31, 28, 24, and 22 nodes, did not align exactly with administrative districts, suggesting the significance of managing livestock infectious diseases beyond governmental borders. In the Partial Least Squares Regression (PLSR) analysis, pig, vehicle, and wild boar movement made comparable positive contributions to PageRank-based node importance within the multilayer network. This study highlights the significance of epidemiological links among husbandry and nonhusbandry stakeholders, emphasizing the need to develop effective risk management tools considering the probable disease transmission pathways.
  • Genetic Diversity of Highly Pathogenic Avian Influenza Viruses Isolated in Hokkaido, Japan, During Winter 2024-2025.
    Norikazu Isoda; Lim Yik Hew; Kazuki Nishikawa; Fumihito Takaya; Yo Shimazu; Daiki Kobayashi; Kei Nabeshima; Hisako Honjyo; Mana Esaki; Kosuke Okuya; Kosuke Soda; Hiroshi Ito; Asuka Kumagai; Hayate Nishiura; Takahiro Hiono; Hiroki Takakuwa; Tatsufumi Usui; Makoto Ozawa; Yuko Uchida; Manabu Onuma; Yoshihiro Sakoda
    Pathogens (Basel, Switzerland), 14, 9, 2025年09月21日, [国際誌]
    英語, 研究論文(学術雑誌), Genetic and antigenic analyses were performed on highly pathogenic avian influenza viruses (HPAIVs) isolated in Hokkaido, northern Japan, during the winter of 2024-2025. Ninety-eight HPAIVs were isolated from feces of waterfowl, tracheal swabs from dead wild birds, or lung homogenates from dead chickens. Phylogenetic analysis of the hemagglutinin (HA) gene from 47 representative isolates revealed that all sequences belonged to the G2d subgroup of clade 2.3.4.4b H5HA, which has been the dominant lineage in Hokkaido since the winter of 2021-2022. These isolates were further divided into three major groups within the subgroup. The HPAIVs isolated in the Republic of Korea, China, and North America were genetically closely related to the Hokkaido isolates, whereas no HPAIVs genetically related to European strains or those detected in North American cattle were identified. Furthermore, HPAIVs isolated from seabirds were genetically closely related to those found in dead marine mammals along the eastern coast of Hokkaido in the spring of 2025. No apparent antigenic differences were observed between the HPAIVs isolated in this study and those from previous seasons. These findings highlight the wide distribution of HPAIVs in Hokkaido, particularly from Asian and North American lineages, and underscore the importance of continuous surveillance.
  • Dynamics of high pathogenicity avian influenza virus infection with multiple introductions in a crow flock in an urban park in Hokkaido, Japan.
    Norikazu Isoda; Takahiro Hiono; Yik Lim Hew; Fumihito Takaya; Bao Linh Nguyen; Daiki Kobayashi; Kaien Fujino; Yoshihiro Sakoda
    Comparative immunology, microbiology and infectious diseases, 121, 102367, 102367, 2025年08月, [国際誌]
    英語, 研究論文(学術雑誌), Since 2021, high pathogenicity avian influenza viruses (HPAIVs) of the H5N1 clade 2.3.4.4b has been circulating globally, not only in domestic poultry but also in wild birds, both migratory and resident species. In March to May 2022, March to April 2023, and January to April 2024, crow die-offs were reported in an urban garden in Hokkaido, Japan, raising suspicions of HPAIV infection. Since August 2022, all dead carcasses were investigated for HPAIV detection and isolation. Phylogenetic analysis of the H5 hemagglutinin gene revealed that all detected HPAIVs belonged to clade 2.3.4.4b, a dominant lineage in Hokkaido since early 2022. Two distinct subgroups were identified: G2d (in 2022-2024) and G2a (in 2024). A maximum clade credibility tree, based on concatenated nucleotide sequences of the isolates, suggested that multiple distinct types of HPAIVs were introduced into the garden in rotation during the winters of 2022-2023 and 2023-2024. Infectious HPAIVs were isolated not only from the lungs and brains but also from the rectal contents of the dead crows, with no apparent difference in viral titers between the two subgroups. The case reproduction numbers of HPAIV infection in the crow flock ranged from 0.52 and 1.57 in the spring of 2022 and from 0.55 to 1.78 in the spring of 2023, suggesting that the contiguous HPAIV infections in the crows were due to multiple introductions into the flock. Crow can play a key role of potential spread to other animals, poultry and wildlife in urban areas or humans in rural areas.
  • Long-term efficacy of an inactivated H5N1 whole-particle influenza vaccine in nonhuman primates.
    Misako Nakayama; Naoko Kitagawa; Cong Thanh Nguyen; Takako Sasamura; Kyoko Takashima; Hirohito Ishigaki; Hideaki Ishida; Saori Suzuki; Yoshihiro Sakoda; Mai Quynh Le; Hiroshi Kida; Kazumasa Ogasawara; Yasushi Itoh
    NPJ vaccines, 10, 1, 164, 164, 2025年07月23日, [国際誌]
    英語, 研究論文(学術雑誌), Outbreaks of H5 highly pathogenic avian influenza A viruses (HPAIVs) in animals pose a threat to humans immunologically naïve to avian influenza viruses. However, annual vaccination, such as for seasonal influenza is not planned because the number of human patients infected with H5 HPAIVs is small, and the possibility of human-to-human transmission of H5 HPAIVs is low at present. However, various clades of H5 HPAIVs have emerged continuously. Therefore, a vaccine that confers long-term and cross-clade immunity is required. To examine the long-term effectiveness and cross-clade reactivity of an H5 influenza virus vaccine, cynomolgus macaques were infected with an H5N1 HPAIV 5 years after two subcutaneous vaccinations with inactivated H5N1 whole-virus particles (H5 clade classical/outlier), which showed higher immunogenicity than did split vaccines in our previous studies. Neutralization titers against the vaccine strain were maintained for 5 years, and a recall immune response was observed on challenge infection against the challenge strain (clade 1) and other H5N1 HPAIV strains (clades 2.2, 2.3.2.1, and 2.3.4.4b). Compared with unvaccinated macaques, viral titers were low, and the cytokine signaling pathways related to the pathogenesis of an influenza virus infection were not activated in the vaccinated macaques. Thus, a whole-virus particle vaccine induced long-term memory sufficient to prevent severe pneumonia caused by an H5N1 HPAIV in cynomolgus macaques.
  • Novel host factors associated with resistance to highly pathogenic avian influenza in wild birds inferred from primary cell culture.
    Kei Nabeshima; Shingo Asakura; Yoshihiro Sakoda; Manabu Onuma
    Scientific reports, 15, 1, 18809, 18809, 2025年05月29日, [国際誌]
    英語, 研究論文(学術雑誌), Bird species differ in the sensitivity to the highly pathogenic avian influenza virus (HPAIV). Here, we infected fibroblasts from 11 bird species with the H5N1 HPAIV strain A/chicken/Yamaguchi/7/2004. These species were categorized into three groups based on previous studies: HPAI-resistant (rock pigeon, hooded crane, white-necked crane, and Japanese crane), HPAI- susceptible (chicken, mountain hawk-eagle, northern goshawk, peregrine falcon, and golden eagle), and those with unknown susceptibility to HPAI (Okinawa rail and Japanese white stork). We performed gene expression analysis to identify genes uniquely upregulated in the HPAI-resistant species and determine genetic markers of HPAIV susceptibility. We found that two genes involved in antiviral response: OAS and IFIT5 expression levels were commonly upregulated after infection in the HPAI-resistant species, but not in the HPAI- susceptible species or species with unknown sensitivity to HPAI. In addition, upregulation ratios of OAS expression at 6 h post-infection and of OAS and IFIT5 at 12 h post-infection were significantly higher in the resistant species than in the susceptible species. We conclude that IFIT5 and OAS could be genetic markers for HPAIV susceptibility, and that Okinawa rail and Japanese white stork are likely susceptible to HPAIV, indicating the need for their conservation and protection against HPAIV infection.
  • Negative impact of porcine circovirus type 2 infection on the efficacy of classical swine fever vaccine in a field farm.
    Keisuke Kuwata; Keko Otsu; Shuko Inoha; Yoko Kimura; Hiroshi Aoki; Yoshihiro Sakoda
    The Journal of veterinary medical science, 87, 5, 509, 516, 2025年05月01日, [国内誌]
    英語, 研究論文(学術雑誌), Porcine circovirus type 2 (PCV2) induces wasting and immunosuppression in pigs and is widely transmitted in pig farms worldwide. Classical swine fever (CSF) is a particularly important contagious disease in pigs. In CSF-endemic areas, such as Japan, thorough vaccination is performed, and effective use of the CSF vaccine is important to prevent outbreaks. This study investigated the impact of PCV2 infection on the immune response to CSF vaccines in field farms. The mortality rate of fattening pigs on the farm was investigated, and pig sera were used to measure the PCV2 viral load and neutralizing antibody titer of CSF as indicators of CSF vaccine efficacy. Results indicated a sharp increase in mortality rate, PCV2 detection rate reaching 100%, and high viral load, whereas CSF antibody titers were significantly lower in the fattening pig herd. After PCV2 inactivated vaccination was initiated, the mortality rate, PCV2 detection rate, and viral load in fattening pigs decreased, and CSF antibody titers also improved. Furthermore, there was a correlation between higher PCV2 viral load and lower CSF antibody titers in this farm. In contrast, other PCV2-vaccinated farms had higher CSF antibody levels. These results indicate that PCV2 infection negatively affects the efficacy of CSF vaccines, and the control of PCV2 in field farms is important.
  • Common host factors for internal ribosomal entry site-mediated translation of viral genomic RNA: An investigation in foot-and-mouth disease and classical swine fever viruses.
    Rupaly Akhter; Kazi Anowar Hossain; Bouchra Kitab; Yoshihiro Sakoda; Kyoko Tsukiyama-Kohara
    Virus research, 355, 199570, 199570, 2025年05月, [国際誌]
    英語, 研究論文(学術雑誌), We previously proposed polycystic kidney disease1-like 3 (PKD1L3) and ubiquitin-specific peptidase 31 (USP31) as potential common host factors for IRES-mediated RNA translation in infections with foot-and-mouth disease virus (FMDV) and classical swine fever virus (CSFV). However, those findings required substantiation, and the specific roles of these factors in the IRES-mediated translation remained unclear. Accordingly, in this study, we aimed to confirm the roles of PKD1L3 and USP31 as host factors associated with IRES activity in bi-cistronic reporter assays, and to investigate the interactions of these host proteins during IRES activity. PKD1L3 and USP31 silencing suppressed IRES activity in both FMDV and CSFV RNAs. PKD1L3 and USP31 overexpression had no significant effects. PKD1L3 and USP31 silencing also suppressed viral RNA replication for CSFV and infection with another picornavirus (from the same family as FMDV), encephalomyocarditis virus. Immunoprecipitation assays revealed that PKD1L3 and USP31 can interact with each other. We also examined their interaction with a eukaryotic translation factor involved in the IRES of hepatitis C virus (HCV), eIF3c. PKD1L3 and more pronouncedly USP31 can interact with eIF3c. Immunofluorescent assays revealed partial, cytoplasmic co-localization of USP31 with PKD1L3, eIF3c, and Hsp90β. Moreover, silencing of eIF3c and Hsp90β suppressed FMDV- and CSFV-IRES activity. Our results indicate the possibility that PKD1L3 and USP31 can participate in IRES activity by interacting with eIF3c and Hsp90β.
  • Enhanced sulfate pseudo-affinity chromatography using monolith-like particle architecture for purifying SARS-CoV-2.
    Kenji Kadoi; Junya Toba; Ayana Uehara; Norikazu Isoda; Yoshihiro Sakoda; Eri Iwamoto
    Vaccine, 53, 126951, 126951, 2025年04月19日, [国際誌]
    英語, 研究論文(学術雑誌), Traditional virus chromatographic purification face limitations owing to the small pore sizes of conventional resins, which restrict efficient virus binding. The newly developed MLP1000 DexS, a cellulose monolith-like particle (MLP) with large continuous pores (radius of 1.5 μm) and a sulfate pseudo-affinity ligand, facilitates virus access to intraparticle surfaces and significantly enhances binding capacity. In this study, we investigated the effectiveness of MLP1000 DexS for purifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from Vero cells. Using a 0.29 mL column volume, we evaluated this resin through bind-elute mode chromatography under two load volume conditions (4.5 mL and 21 mL). MLP1000 DexS exhibited superior performance under high-loading conditions, achieving a high elution recovery of 59 % for the virus compared with that of 11-17 % for the commercial resins Cellufine Sulfate and Capto DeVirS. Additionally, the dsDNA removal capacity of MLP1000 DexS was 3.0-5.3-fold higher than that of the other resins. These findings suggest that MLP1000 DexS is an effective purification material for the downstream processing of live-attenuated and inactivated coronavirus vaccine production.
  • Potency of two chimeric vaccine candidates derived from the classical swine fever GPE- vaccine strain against a circulating virus strain isolated in Japan.
    Tatsuya Nishi; Loc Tan Huynh; Tomoko Kato; Mitsutaka Ikezawa; Takehisa Yamamoto; Yoshihiro Sakoda; Katsuhiko Fukai
    Veterinary microbiology, 303, 110438, 110438, Elsevier BV, 2025年04月, [国際誌]
    英語, 研究論文(学術雑誌), A classical swine fever (CSF) vaccine combining high potency and an immunological marker for differentiating infected animals from vaccinated animals facilitates disease control and provides proof of eradication to promote international pig trade. Previously, CSF virus (CSFV) recombinant live vaccine strains, guinea-pig exaltation of Newcastle disease virus-negative strain vaccine [vGPE- (genotype 1.1)], were developed with the Erns gene replaced by non-CSF pestiviruses (Pronghorn antelope or Phocoena pestiviruses). We evaluated the potency of these marker vaccines against a Japanese circulating CSFV strain (genotype 2.1), which is genetically distant from the vaccine strain. Pigs were experimentally vaccinated with the vGPE- and two marker vaccine strains. All vaccinated and unvaccinated pigs were challenged with CSFV JPN/1/2018 at 26 days post-vaccination. The clinical signs and viral titers in blood and oral swabs were monitored for three weeks post-challenge, and antibodies against CSFV E2 and Erns were detected using commercial enzyme-linked immunosorbent assay kits. Unvaccinated pigs showed typical CSF clinical signs and viremia, and one pig died at 19 days post-challenge. Meanwhile, none of the vaccinated pigs showed any clinical signs, and the replication of infectious virus was substantially suppressed. Both vGPE--vaccinated and unvaccinated pigs had CSFV E2 and Erns antibodies after vaccination and virus challenge; meanwhile, notably, marker-vaccinated pigs had only E2 antibodies, while both E2 and Erns antibodies detected only after the challenge. In conclusion, the marker vaccine strains provided protective immunity to suppress clinical signs, viremia, and virus excretion, comparable to the GPE- live vaccine, and successfully differentiated infection from vaccination.
  • Altered receptor-binding specificity of gull-adapted H13 avian influenza viruses corresponds to their unique host preferences.
    Rio Harada; Takahiro Hiono; Manabu Igarashi; Daiki Kobayashi; Hinako Ban; Norikazu Isoda; Yoshihiro Sakoda
    Virology, 605, 110460, 110460, 2025年04月, [国際誌]
    英語, 研究論文(学術雑誌), Avian influenza viruses (AIVs) recognize α2-3 sialosides as receptors. Previous studies showed that the structural diversity within α2-3 sialosides is related to the host specificity of AIVs. H13 AIVs are primarily isolated from gulls, although almost all AIV subtypes have been isolated from ducks, the natural hosts of AIVs. To elucidate the molecular basis of the host specificity of H13 viruses to gulls, the receptor-binding specificity of H13 hemagglutinins (HAs) and the distribution of viral receptors in gulls were investigated. The results revealed that recombinant HA (rHA) of H13 viruses had a binding preference for fucosylated α2-3 sialosides, which were distributed widely in the respiratory tract and intestines of gulls but not in the colon of ducks. Moreover, the receptor-binding specificity of mutant rHAs revealed that amino acids in the 130-loop and at position 227 of H13 HA were critical for the preference for fucosylated α2-3 sialosides. The results of the present study suggest that the binding specificity of H13 HA to fucosylated α2-3 sialosides is a key factor for the host susceptibility of H13 viruses to gulls.
  • Deglycosylation and truncation in the neuraminidase stalk are functionally equivalent in enhancing the pathogenicity of a high pathogenicity avian influenza virus in chickens.
    Daiki Kobayashi; Takahiro Hiono; Hiromu Arakawa; Hiroyuki Kaji; Ayako Ohkawara; Takaya Ichikawa; Hinako Ban; Norikazu Isoda; Yoshihiro Sakoda
    Journal of virology, 99, 3, e0147824, 2025年03月18日, [国際誌]
    英語, 研究論文(学術雑誌), Influenza A viruses with fewer amino acids in the neuraminidase (NA) stalk domain are primarily isolated from chickens rather than wild ducks, indicating that a shortened NA stalk is considered an adaptation marker of avian influenza viruses (AIVs) to chickens. Experimental passages of an H7N7 nonpathogenic AIV (rgVac2-P0) in chickens resulted in a highly pathogenic variant (Vac2-P3L4) with a 34-amino-acid deletion in the NA stalk, encompassing five potential N-glycosylation sites. To investigate how amino acid truncation and deglycosylation in the NA stalk contribute to increased pathogenicity, a virus with glycosylation-deficient mutations at these sites (rgVac2-P3L4/P0NAΔGlyco) was constructed. Contrary to expectations, chickens inoculated with rgVac2-P3L4/P0NAΔGlyco exhibited variable clinical outcomes, attributed to the genetic instability of the virus. A single mutation stabilized the virus, and the mutant (rgVac2-P3L4/P0NAΔGlyco-Y65H) resulted in higher pathogenicity compared with a virus with restored glycosylation (rgVac2-P3L4/P0NA-Y65H). Glycan occupancy analysis revealed 3-4 glycans at the five potential sites. In functional analysis, glycosylation-deficient mutants, similar to the short-stalk NA virus, showed significantly reduced erythrocyte elution activity. Additionally, mutational analysis indicated variable contributions of N-glycans to elution activity across the sites. Moreover, the functionally most contributing sites of the five potential N-glycosylation motifs were consistently included in the amino acid deletions of the stalk-truncated NA in N7-subtyped field isolates, despite the varying truncation position or length. These findings suggest that the loss of glycosylation is functionally equivalent to a reduction in amino acids, and it plays a crucial role in enhancing pathogenicity in chickens and affecting NA function.IMPORTANCEAvian influenza poses significant economic challenges to the poultry industry and presents potential risks to human health. Understanding the molecular mechanisms that facilitate the emergence of chicken-adapted avian influenza viruses (AIVs) from non-pathogenic duck-origin influenza viruses is crucial for improving AIV monitoring systems in poultry and controlling this disease. Amino acid deletions in the neuraminidase (NA) stalk domain serve as one of the molecular markers for AIV adaptation to Galliformes. This study highlights the critical role of N-glycosylation in the NA stalk domain in the pathogenesis of high pathogenicity avian influenza viruses in chickens. The findings propose a novel theory that the loss of glycosylation at the NA stalk domain, rather than a reduction in stalk length, is responsible for both NA function and increased virus pathogenicity in chickens.
  • Generation of Vaccine Candidate Strains That Antigenically Match Classical Swine Fever Virus Field Strains.
    Maya Kobayashi; Loc Tan Huynh; Saho Ogino; Lim Yik Hew; Miki Koyasu; Hikaru Kamata; Takahiro Hiono; Norikazu Isoda; Yoshihiro Sakoda
    Vaccines, 13, 2, 2025年02月14日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Classical swine fever virus (CSFV) is genetically categorized into three genotypes. A live-attenuated vaccine strain GPE-, currently used in Japan, belongs to genotype 1 and is genetically distinct from the field strains circulating in Japan, which belong to genotype 2. This study aimed to understand the antigenicity of recent field isolates in Japan and develop new vaccine candidates that antigenically match field strains. METHODS: The serum samples of 20 pigs vaccinated with GPE- were subjected to a serum neutralizing test (SNT) using one of the field strains, CSFV/wb/Jpn-Mie/P96/2019 (Mie/2019). For the antigenic matching, vGPE-/HiBiT/Mie E2 was generated by replacing the viral glycoprotein E2, the main target of the neutralizing antibody, with that of Mie/2019. Additionally, vGPE-/HiBiT/Mie E2/PAPeV Erns was generated by further substituting glycoprotein Erns with that of pronghorn antelope pestivirus (PAPeV) since Erns is not important as a vaccine immunogen and can be replaced by that of other pestiviruses to provide an immunological marker. The efficacy of vGPE-/HiBiT/Mie E2/PAPeV Erns was further evaluated by the challenge experiments in pigs. RESULTS: The SNT titers of serum sample against Mie/2019 were 6.1-fold lower than that against vGPE-. The generated recombinant viruses showed closer antigenicity to Mie/2019 than vGPE-. The challenge study confirmed that vGPE-/HiBiT/Mie E2/PAPeV Erns provided clinical and virological protection against a field CSFV equivalent to vGPE-. CONCLUSIONS: This study demonstrated that swapping the E2 encoding region with the prevalent field CSFVs is a promising strategy to achieve antigenic matching between the vaccine and field strains.
  • Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys.
    Fumihiko Yasui; Keisuke Munekata; Tomoko Fujiyuki; Takeshi Kuraishi; Kenzaburo Yamaji; Tomoko Honda; Sumiko Gomi; Misako Yoneda; Takahiro Sanada; Koji Ishii; Yoshihiro Sakoda; Hiroshi Kida; Shosaku Hattori; Chieko Kai; Michinori Kohara
    Vaccines, 13, 1, 2025年01月15日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND/OBJECTIVES: In preparation for a potential pandemic caused by the H5N1 highly pathogenic avian influenza (HPAI) virus, pre-pandemic vaccines against several viral clades have been developed and stocked worldwide. Although these vaccines are well tolerated, their immunogenicity and cross-reactivity with viruses of different clades can be improved. METHODS: To address this aspect, we generated recombinant influenza vaccines against H5-subtype viruses using two different strains of highly attenuated vaccinia virus (VACV) vectors. RESULTS: rLC16m8-mcl2.2 hemagglutinin (HA) and rLC16m8-mcl2.3.4 HA consisted of a recombinant LC16m8 vector encoding the HA protein from clade 2.2 or clade 2.3.4 viruses (respectively); rDIs-mcl2.2 HA consisted of a recombinant DIs vector encoding the HA protein from clade 2.2. A single dose of rLC16m8-mcl2.2 HA showed rapid (1 week after vaccination) and long-term protection (20 months post-vaccination) in mice against the HPAI H5N1 virus. Moreover, cynomolgus macaques immunized with rLC16m8-mcl2.2 HA exhibited long-term protection when challenged with a heterologous clade of the HPAI H5N1 virus. Although the DIs strain is unable to grow in most mammalian cells, rDIs-mcl2.2 HA also showed rapid and long-lasting effects against HPAI H5N1 virus infection. Notably, the protective efficacy of rDIs-mcl2.2 HA was comparable to that of rLC16m8-mcl2.2 HA. Furthermore, these vaccines protected animals previously immunized with VACVs from a lethal challenge with the HPAI H5N1 virus. CONCLUSIONS: These results suggest that both rLC16m8-mcl2.2 HA and rDIs-mcl2.2 HA are effective in preventing HPAI H5N1 virus infection, and rDIs-mcl2.2 HA is a promising vaccine candidate against H5 HA-subtype viruses.
  • Serosurvey of Bovine Viral Diarrhea Virus in Cattle in Southern Japan and Estimation of Its Transmissibility by Transient Infection in Nonvaccinated Cattle.
    Norikazu Isoda; Satoshi Sekiguchi; Chika Ryu; Kosuke Notsu; Maya Kobayashi; Karin Hamaguchi; Takahiro Hiono; Yuichi Ushitani; Yoshihiro Sakoda
    Viruses, 17, 1, 2025年01月02日, [国際誌]
    英語, 研究論文(学術雑誌), Bovine viral diarrhea (BVD) is caused by the BVD virus (BVDV) and has been reported worldwide in cattle. To estimate BVDV circulation among cattle where few BVD cases were reported in southern Japan, 1910 serum samples collected from 35 cattle farms without a BVD outbreak were investigated to detect antibodies against BVDV-1 and BVDV-2 using an indicator virus with a cytopathogenic effect and the luciferase gene, respectively. Neutralizing antibodies against BVDV-1 and BVDV-2 were detected more frequently in 18 vaccinated farms than in 17 nonvaccinated farms. In the nonvaccinated farms, 9.6%, 1.8%, and 13.8% of the cattle were estimated to have a history of infection with BVDV-1, BVDV-2, and both, respectively. The median rate of within-herd anti-BVDV-1 seropositivity among cattle in the nonvaccinated farms was 22.0%; however, a high within-herd seropositivity (>50%) was confirmed in the two farms. The force of infection, basic reproduction number, and annual probability of BVDV-1 infection were estimated as 0.072 (95% confidence interval [CI]: 0.062-0.084), 0.36 (95% CI: 0.31-0.42), and 0.73% (95% CI: 0.61-0.87%), respectively, using the age-specific positive rate of anti-BVDV-1 antibodies. These parameters should be further applicable for developing epidemiological models which illustrate the BVDV dynamics in the field.
  • Edible bird's nest: N- and O-glycan analysis and synergistic anti-avian influenza virus activity with neuraminidase inhibitors.
    Nongluk Sriwilaijaroen; Hisatoshi Hanamatsu; Ikuko Yokota; Takashi Nishikaze; Tetsuo Ijichi; Tadanobu Takahashi; Yoshihiro Sakoda; Jun-Ichi Furukawa; Yasuo Suzuki
    Antiviral research, 232, 106040, 106040, 2024年12月, [国際誌]
    英語, 研究論文(学術雑誌), Zoonotic avian influenza viruses have continued to infect people on occasion. During treatment, antiviral resistant viruses have occasionally emerged, highlighting the need for a novel strategy for treating human illness. After pancreatin treatment, edible bird's nest (EBN), swiftlet saliva consumed for health purposes, possesses anti-avian viral activity by inhibiting receptor-binding hemagglutinin (HA) activity. Glycan analysis revealed an abundance of α2,3Neu5Ac decoy receptors in pancreatin-treated EBN. Fucosylated tri-α2,3Neu5Ac tri-antennary N-glycans (N-35) and di-α2,3Neu5Ac core 2 O-glycans (O-15) are predominant, accounting for 53.46% and 44.66% of total N- and O-glycan amounts, respectively. Isobologram analysis revealed that the treated EBN had a strong synergistic effect with either oseltamivir carboxylate or zanamivir, a competitive inhibitor of receptor-destroying neuraminidases (NAs), against the avian H5N1 virus. Taken together, EBN has the potential to be developed as a food-derived avian viral trap to prevent and decrease avian virus infection as well as in combination with a viral releasing-NA inhibitor to increase therapeutic potency, reduce toxicity, delay resistance development, and potentially prevent pandemic onset.
  • Genome sequencing of canine distemper virus isolates from unvaccinated dogs in Mongolia.
    Ariunbold Munkhtsetseg; Enkhbaatar Batmagnai; Myagmarsuren Odonchimeg; Gombodash Ganbat; Yondonjamts Enkhmandakh; Gantulga Ariunbold; Tsedenbal Dolgorsuren; Raadan Odbileg; Purevtseren Dulam; Bumduuren Tuvshintulga; Chihiro Sugimoto; Yoshihiro Sakoda; Junya Yamagishi; Dashzevge Erdenechimeg
    Veterinary journal (London, England : 1997), 308, 106231, 106231, 2024年12月, [国際誌]
    英語, 研究論文(学術雑誌), Canine distemper virus (CDV) triggers a severe, often fatal disease in dogs and wildlife known as canine distemper (CD). Prior research has noted significant genetic diversity and recombination among CDV isolates from different geographical regions, potentially contributing to vaccine failures. Despite this, no genetic characterization of Mongolian CDVs has been conducted. This study, isolated CDVs from three unvaccinated dogs: two 10-month-old mixed-breeds and an 18-month-old Samoyed. All exhibited CD symptoms and subsequently died. Virus isolation was conducted using Vero/dog SLAM cells, with genome sequencing performed via nanopore technology. The mixed-breed dogs were infected with non-recombinant CDV isolates, forming a sister clade to the Asia-1 lineage prevalent in Asia. The Samoyed was infected with a non-recombinant CDV isolate, classifying as Asia-4 lineage sporadically reported in some Asian countries. This sequencing data offers foundational information on genetic diversity, aiding CD control measure development and benefiting future Eurasia and Asian studies.
  • Hemagglutinin and neuraminidase of a non-pathogenic H7N7 avian influenza virus coevolved during the acquisition of intranasal pathogenicity in chickens.
    Takaya Ichikawa; Takahiro Hiono; Masatoshi Okamatsu; Junki Maruyama; Daiki Kobayashi; Keita Matsuno; Hiroshi Kida; Yoshihiro Sakoda
    Archives of virology, 169, 10, 207, 207, 2024年09月22日, [国際誌]
    英語, 研究論文(学術雑誌), Polybasic amino acid residues at the hemagglutinin (HA) cleavage site are insufficient to induce the highly pathogenic phenotype of avian influenza viruses in chickens. In our previous study, an H7N7 avian influenza virus named "Vac2sub-P0", which is nonpathogenic despite carrying polybasic amino acids at the HA cleavage site, was passaged in chick air sacs, and a virus with high intravenous pathogenicity, Vac2sub-P3, was obtained. Intranasal infection with Vac2sub-P3 resulted in limited lethality in chickens; therefore, in this study, this virus was further passaged in chicken lungs, and the resultant virus, Vac2sub-P3L4, acquired high intranasal pathogenicity. Experimental infection of chickens with recombinant viruses demonstrated that mutations in HA and neuraminidase (NA) found in consecutive passages were responsible for the increased pathogenicity. The HA and NA functions of Vac2sub-P3L4 were compared with those of the parental virus in vitro; the virus growth at 40 °C was faster, the binding affinity to a sialic acid receptor was lower, and the rate of release by NA from the cell surface was lower, suggesting that these changes enabled the virus to replicate efficiently in chickens with high intranasal pathogenicity. This study demonstrates that viruses that are highly pathogenic when administered intranasally require additional adaptations for increased pathogenicity to be highly lethal to intranasally infected chickens.
  • Cocirculation of Genetically Distinct Highly Pathogenic Avian Influenza H5N5 and H5N1 Viruses in Crows, Hokkaido, Japan.
    Yik Lim Hew; Takahiro Hiono; Isabella Monne; Kei Nabeshima; Saki Sakuma; Asuka Kumagai; Shunya Okamura; Kosuke Soda; Hiroshi Ito; Mana Esaki; Kosuke Okuya; Makoto Ozawa; Toshiyo Yabuta; Hiroki Takakuwa; Linh Bao Nguyen; Norikazu Isoda; Kohtaro Miyazawa; Manabu Onuma; Yoshihiro Sakoda
    Emerging infectious diseases, 30, 9, 1912, 1917, 2024年09月, [国際誌]
    英語, 研究論文(学術雑誌), We isolated highly pathogenic avian influenza (HPAI) H5N5 and H5N1 viruses from crows in Hokkaido, Japan, during winter 2023-24. They shared genetic similarity with HPAI H5N5 viruses from northern Europe but differed from those in Asia. Continuous monitoring and rapid information sharing between countries are needed to prevent HPAI virus transmission.
  • Molecular characterization of an avian rotavirus a strain detected from a large-billed crow (Corvus macrorhynchos) in Japan.
    Yuji Fujii; Tatsunori Masatani; Shoko Nishiyama; Tatsuki Takahashi; Misuzu Okajima; Fumiki Izumi; Yoshihiro Sakoda; Ayato Takada; Makoto Ozawa; Makoto Sugiyama; Naoto Ito
    Virology, 596, 110114, 110114, 2024年08月, [国際誌]
    英語, 研究論文(学術雑誌), Avian rotaviruses A (RVAs) are occasionally transmitted to animals other than the original hosts across species barriers. Information on RVAs carried by various bird species is important for identifying the origin of such interspecies transmission. In this study, to facilitate an understanding of the ecology of RVAs from wild birds, we characterized all of the genes of an RVA strain, JC-105, that was detected in a fecal sample of a large-billed crow (Corvus macrorhynchos) in Japan. All of the genes of this strain except for the VP4 and VP7 genes, which were classified as novel genotypes (P[56] and G40, respectively), were closely related to those of the avian-like RVA strain detected from a raccoon, indicating the possibility that crows had been involved in the transmission of avian RVAs to raccoons. Our findings highlight the need for further viral investigations in wild birds and mammals to understand the mechanisms of avian-to-mammal RVA transmission.
  • Evaluation of Immune Status of Pigs against Classical Swine Fever for Three Years after the Initiation of Vaccination in Gifu Prefecture, Japan.
    Keisuke Kuwata; Naotoshi Kuninaga; Yoko Kimura; Kohei Makita; Norikazu Isoda; Yukio Shimizu; Yoshihiro Sakoda
    Pathogens (Basel, Switzerland), 13, 8, 2024年07月25日, [国際誌]
    英語, 研究論文(学術雑誌), In 2018, classical swine fever (CSF) reemerged in Gifu Prefecture, Japan, after 26 years of absence, and vaccination of domestic pigs using a live attenuated vaccine was initiated in 2019. Because the vaccine efficacy in piglets is influenced by the maternal antibody levels, vaccination should be administered at the optimal age by assuming the antibody level in sows. In this study, the shift in the antibody titer distribution in sows due to the initiation of vaccination to naïve herds and its influence on the vaccine-induced immunity rate in fattening pigs were investigated for 3 years. The results indicated that higher antibody titers were induced in first-generation sows after vaccine initiation because they were immunologically naïve, but the distribution of antibody titers shifted to lower levels along with their replacement with second-generation sows. The average vaccination age of fattening pigs became earlier year by year, and the vaccine-induced antibody rate was almost ≥80%. Based on the estimation of the optimal age for vaccination, it was found that vaccination at a younger age may reduce the risk of CSF infection. Taken together, the risk of CSF outbreaks can be reduced by administering vaccines at the optimal age based on the sequential monitoring of the sow's immune status.
  • Assessment of the Safety Profile of Chimeric Marker Vaccine against Classical Swine Fever: Reversion to Virulence Study.
    Loc Tan Huynh; Mikihiro Otsuka; Maya Kobayashi; Hung Dinh Ngo; Lim Yik Hew; Takahiro Hiono; Norikazu Isoda; Yoshihiro Sakoda
    Viruses, 16, 7, 2024年07月12日, [国際誌]
    英語, 研究論文(学術雑誌), Chimeric marker vaccine candidates, vGPE-/PAPeV Erns and vGPE-/PhoPeV Erns, have been generated and their efficacy and capability to differentiate infected from vaccinated animals were confirmed in previous studies. The safety profile of the two chimeric marker vaccine candidates, particularly in the potential reversion to virulence, was evaluated. Each virus was administered to pigs with a dose equivalent to the vaccination dose, and pooled tonsil homogenates were subsequently inoculated into further pigs. Chimeric virus vGPE-/PAPeV Erns displayed the most substantial attenuation, achieving this within only two passages, whereas vGPE-/PhoPeV Erns was detectable until the third passage and disappeared entirely by the fourth passage. The vGPE- strain, assessed alongside, consistently exhibited stable virus recovery across each passage without any signs of increased virulence in pigs. In vitro assays revealed that the type I interferon-inducing capacity of vGPE-/PAPeV Erns was significantly higher than that of vGPE-/PhoPeV Erns and vGPE-. In conclusion, the safety profile of the two chimeric marker vaccine candidates was affirmed. Further research is essential to ensure the stability of their attenuation and safety in diverse pig populations.
  • 宮崎県における牛ウイルス性下痢の積極的疫学調査と分離株の遺伝子系統解析
    野津 昂亮; 龍 千香; Ul Hakim Bin Rahmat Luqman; Ullah Shakir; 植木 萌葉; 三苫 修也; 乗峰 潤三; 青木 博史; 亀山 健一郎; 迫田 義博; 関口 敏
    獣医疫学雑誌, 28, 1, 20, 21, 獣医疫学会, 2024年07月
    日本語
  • Phylogenetic analysis of small ruminant lentiviruses in Mongolian sheep supports an ancient east-west split for the genotype A.
    Nergui Davaasuren; Vahid Molaee; Tseren-Ochir Erdene-Ochir; Guugandaa Nyamdavaa; Sumiya Ganzorig; Maurizio Mazzei; Yoshihiro Sakoda; Gesine Lühken; Sharav Tumenjargal
    Veterinary research communications, 48, 3, 1955, 1962, 2024年06月, [国際誌]
    英語, 研究論文(学術雑誌), The ovine maedi-visna virus (MVV) and caprine arthritis-encephalitis virus (CAEV) are small ruminant lentiviruses (SRLVs) with striking genetic and structural similarities. The presence of SRLV in Mongolian sheep and goats was serologically demonstrated more than a decade ago; however, the viral genotype remains unknown. In total, 329 blood samples were collected from two sheep breeds (i.e., Khalkha and Sumber) in Tov, Govisumber, Arkhangay, Dornogovi, Zavkhan, and Sukhbaatar provinces, Mongolia. Serological and phylogenetic analyses were performed regardless of any apparent clinical signs, although most of the animals appeared healthy. All sheep in three of the six provinces were seronegative, whereas the seroprevalence in the Tov, Govisumber, and Zavkhan provinces averaged 7.9%. Genomic DNA from seropositive animals was tested using hemi-nested polymerase chain reaction, and sub-genomic SRLV sequences were determined from nine samples. Mongolian SRLV sequences clustered within the divergent subtype A22, which was previously found only in Fertile Crescent regions, including Lebanon, Jordan, and Iran, where the first sheep-domestication (Ovis aries) occurred. According to the phylogenetic analysis, genotype A has two ancestors from the ancient Fertile Crescent: (1) Turkish strains and (2) Iranian, Jordanian, and Lebanese strains. The first ancestor spread westward, whereas the second spread eastward, ultimately reaching Mongolia.
  • FOUR-WEEK ORAL ADMINISTRATION OF BALOXAVIR MARBOXIL AS AN ANTI-INFLUENZA VIRUS DRUG SHOWS NO TOXICITY IN CHICKENS.
    Mariko Miki; Ryo Daniel Obara; Kyohei Nishimura; Takao Shishido; Yoshinori Ikenaka; Ryoko Oka; Kenji Sato; Shouta M M Nakayama; Takashi Kimura; Atsushi Kobayashi; Keisuke Aoshima; Keisuke Saito; Takahiro Hiono; Norikazu Isoda; Yoshihiro Sakoda
    Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians, 55, 2, 313, 321, 2024年06月, [国際誌]
    英語, 研究論文(学術雑誌), High pathogenicity avian influenza is an acute zoonotic disease with high mortality in birds caused by a high pathogenicity avian influenza virus (HPAIV). Recently, HPAIV has rapidly spread worldwide and has killed many wild birds, including endangered species. Baloxavir marboxil (BXM), an anti-influenza agent used for humans, was reported to reduce mortality and virus secretion from HPAIV-infected chickens (Gallus domesticus, order Galliformes) at a dosage of ≥2.5 mg/kg when administered simultaneously with viral challenge. Application of this treatment to endangered birds requires further information on potential avian-specific toxicity caused by repeated exposure to BXM over the long term. To obtain information of potential avian-specific toxicity, a 4-wk oral repeated-dose study of BXM was conducted in chickens (n = 6 or 7 per group), which are commonly used as laboratory avian species. The study was conducted in reference to the human pharmaceutical guidelines for nonclinical repeated-dose drug toxicity studies to evaluate systemic toxicity and exposure. No adverse changes were observed in any organs examined, and dose proportional increases in systemic exposure to active pharmaceutical ingredients were noted from 12.5 to 62.5 mg/kg per day. BXM showed no toxicity to chickens at doses of up to 62.5 mg/kg per day, at which systemic exposure was approximately 71 times higher than systemic exposure at 2.5 mg/kg, the reported efficacious dosage amount, in HPAIV-infected chickens. These results also suggest that BXM could be considered safe for treating HPAIV-infected endangered birds due to its high safety margin compared with the efficacy dose. The data in this study could contribute to the preservation of endangered birds by using BXM as a means of protecting biodiversity.
  • Development of a dual immunochromatographic test strip to detect E2 and Erns antibodies against classical swine fever
    Loc Tan Huynh; Eun-Ju Sohn; Youngmin Park; Juhun Kim; Tomohiko Shimoda; Takahiro Hiono; Norikazu Isoda; Sung-Hee Hong; Ha-Na Lee; Yoshihiro Sakoda
    Frontiers in Microbiology, 15, 1383976, 1383976, Frontiers Media SA, 2024年04月11日, [国際誌]
    英語, 研究論文(学術雑誌), Background

    It is essential to consider a practical antibody test to successfully implement marker vaccines and validate vaccination efficacy against classical swine fever virus (CSFV). The test should include a serological antibody assay, combined with a tool for differentiating infected from vaccinated animals (DIVA). The immunochromatographic test strip (ICS) has been exclusively designed for detecting CSFV E2 antibodies while lacking in detecting Erns antibodies, which can be employed and satisfy DIVA strategy. This study developed a novel ICS for detecting CSFV E2/Erns dual-antibody. The effectiveness of ICS in evaluating the DIVA capability of two novel chimeric pestivirus vaccine candidates was assessed.

    Methods

    Recombinant E2 or Erns protein was transiently expressed in the plant benthamiana using Agrobacterium tumefaciens. ICS was subsequently assembled, and goat anti-rabbit IgG and recombinant CSFV E2 or Erns protein were plated onto the nitrocellulose membrane as control and test lines, respectively. The sensitivity and specificity of ICS were evaluated using sera with different neutralizing antibody titers or positive for antibodies against CSFV and other pestiviruses. The coincidence rates for detecting E2 and Erns antibodies between ICS and commercial enzyme-linked immunosorbent assay (ELISA) kits were also computed. ICS performance for DIVA capability was evaluated using sera from pigs vaccinated with conventional vaccine or chimeric vaccine candidates.

    Results

    E2 and Erns proteins were successfully expressed in N. benthamiana-produced recombinant proteins. ICS demonstrated high sensitivity in identifying CSFV E2 and Erns antibodies, even at the low neutralizing antibody titers. No cross-reactivity with antibodies from other pestiviruses was confirmed using ICS. There were high agreement rates of 93.0 and 96.5% between ICS and two commercial ELISA kits for E2 antibody testing. ICS also achieved strong coincidence rates of 92.9 and 89.3% with two ELISA kits for Erns antibody detection. ICS confirmed the absence of CSFV Erns-specific antibodies in sera from pigs vaccinated with chimeric vaccine candidates.

    Conclusion

    E2 and Erns proteins derived from the plant showed great potential and can be used to engineer a CSFV E2/Erns dual-antibody ICS. The ICS was also highly sensitive and specific for detecting CSFV E2 and Erns antibodies. Significantly, ICS can fulfill the DIVA concept by incorporating chimeric vaccine candidates.
  • Continuous Introduction of H5 High Pathogenicity Avian Influenza Viruses in Hokkaido, Japan: Characterization of Viruses Isolated in Winter 2022–2023 and Early Winter 2023–2024
    Lim Yik Hew; Norikazu Isoda; Fumihito Takaya; Kohei Ogasawara; Daiki Kobayashi; Loc Tan Huynh; Tatsuru Morita; Rio Harada; Nikolay Gennadievich Zinyakov; Dmitriy Borisovich Andreychuk; Ilya Alexandrovich Chvala; Viktor Nikolaevich Irza; Yukiko Watanabe; Hiroko Fujita; Keisuke Saito; Takahiro Hiono; Yoshihiro Sakoda
    Transboundary and Emerging Diseases, 2024, 1, 18, Hindawi Limited, 2024年03月14日
    研究論文(学術雑誌), High pathogenicity avian influenza (HPAI) has impacted poultry and wild birds globally. The number of H5 HPAI virus (HPAIV) infection cases in wild birds in Hokkaido (Northern Japan) was high in the last two seasons, contributing to virus spillover to resident birds and poultry. Therefore, H5 HPAIVs in birds and mammals in Hokkaido in winter 2022–2023 and 2023–2024 were monitored and viruses were phylogenetically, antigenically, and pathogenetically characterized. Thirty HPAIV isolates were subtyped and pathotyped by sequencing the hemagglutinin (HA) gene of viruses. Phylogenetic analysis of the HA gene revealed that all isolated HPAIVs were categorized into clade 2.3.4.4b and divided into three groups (G2b, G2c, and G2d). Most isolates belonging to subgroup G2d clustered with isolates in winter 2021–2022 in Hokkaido. The other isolates were categorized into two subgroups, G2b and G2c, mainly composed of isolates in Honshu Island in winter 2021–2022 and 2022–2023, respectively. Two H5 HPAIVs isolated in Eastern Russia in spring and autumn 2022 were genetically close to most Hokkaido isolates (G2d), and a virus isolated in Hokkaido in November 2023 was also grouped in subgroup G2d. Further analysis of all eight gene segments identified six types of gene constellations. Cross-hemagglutination inhibition test indicated that the antigenicity of H5 HPAIVs isolated in the last several seasons was similar within them but slightly different from that in the 2010s. Three chicken breeds were intranasally challenged with four representative isolates to assess their pathogenicity. All chickens except one broiler chicken were dead until 5-day postchallenge with different pathogenicity of these viruses. The pathogenicity of one HPAIV strain was significantly lower in broiler chickens than in layer chickens. The mixture of multiple characteristics of HPAIVs in Hokkaido was confirmed by bird migration routes. Thus, many HPAIVs can be brought and scattered anywhere on Earth.
  • A rapid and versatile reverse genetics approach for generating recombinant positive-strand RNA viruses that use IRES-mediated translation.
    Tomokazu Tamura; Hirotaka Yamamoto; Saho Ogino; Yuhei Morioka; Shuhei Tsujino; Rigel Suzuki; Takahiro Hiono; Saori Suzuki; Norikazu Isoda; Yoshihiro Sakoda; Takasuke Fukuhara
    Journal of virology, 98, 3, e0163823, 2024年02月14日, [国際誌]
    英語, 研究論文(学術雑誌), Reverse genetics systems have played a central role in developing recombinant viruses for a wide spectrum of virus research. The circular polymerase extension reaction (CPER) method has been applied to studying positive-strand RNA viruses, allowing researchers to bypass molecular cloning of viral cDNA clones and thus leading to the rapid generation of recombinant viruses. However, thus far, the CPER protocol has only been established using cap-dependent RNA viruses. Here, we demonstrate that a modified version of the CPER method can be successfully applied to positive-strand RNA viruses that use cap-independent, internal ribosomal entry site (IRES)-mediated translation. As a proof-of-concept, we employed mammalian viruses with different types (classes I, II, and III) of IRES to optimize the CPER method. Using the hepatitis C virus (HCV, class III), we found that inclusion in the CPER assembly of an RNA polymerase I promoter and terminator, instead of those from polymerase II, allowed greater viral production. This approach was also successful in generating recombinant bovine viral diarrhea virus (class III) following transfection of MDBK/293T co-cultures to overcome low transfection efficiency. In addition, we successfully generated the recombinant viruses from clinical specimens. Our modified CPER could be used for producing hepatitis A virus (HAV, type I) as well as de novo generation of encephalomyocarditis virus (type II). Finally, we generated recombinant HCV and HAV reporter viruses that exhibited replication comparable to that of the wild-type parental viruses. The recombinant HAV reporter virus helped evaluate antivirals. Taking the findings together, this study offers methodological advances in virology.IMPORTANCEThe lack of versatility of reverse genetics systems remains a bottleneck in viral research. Especially when (re-)emerging viruses reach pandemic levels, rapid characterization and establishment of effective countermeasures using recombinant viruses are beneficial in disease control. Indeed, numerous studies have attempted to establish and improve the methods. The circular polymerase extension reaction (CPER) method has overcome major obstacles in generating recombinant viruses. However, this method has not yet been examined for positive-strand RNA viruses that use cap-independent, internal ribosome entry site-mediated translation. Here, we engineered a suitable gene cassette to expand the CPER method for all positive-strand RNA viruses. Furthermore, we overcame the difficulty of generating recombinant viruses because of low transfection efficiency. Using this modified method, we also successfully generated reporter viruses and recombinant viruses from a field sample without virus isolation. Taking these findings together, our adapted methodology is an innovative technology that could help advance virologic research.
  • Phylogenetic Analysis of Newcastle Disease Virus Isolated from Poultry in Live Bird Markets and Wild Waterfowl in Zambia.
    Annie Kalonda; Ngonda Saasa; Masahiro Kajihara; Naganori Nao; Ladslav Moonga; Joseph Ndebe; Akina Mori-Kajihara; Andrew Nalishuwa Mukubesa; Yoshihiro Sakoda; Hirofumi Sawa; Ayato Takada; Edgar Simulundu
    Microorganisms, 12, 2, 2024年02月08日, [国際誌]
    英語, 研究論文(学術雑誌), Poultry production is essential to the economy and livelihood of many rural Zambian households. However, the industry is threatened by infectious diseases, particularly Newcastle disease virus (NDV) infection. Therefore, this study employed next-generation sequencing to characterise six NDV isolates from poultry in Zambia's live bird markets (LBMs) and wild waterfowl. Four NDV isolates were detected from 410 faecal samples collected from chickens in LBMs in Lusaka and two from 2851 wild birds from Lochinvar National Park. Phylogenetic analysis revealed that the four NDVs from LBM clustered in genotype VII and sub-genotype VII.2 were closely related to viruses previously isolated in Zambia and other Southern African countries, suggesting possible local and regional transboundary circulation of the virus. In contrast, the two isolates from wild birds belonged to class I viruses, genotype 1, and were closely related to isolates from Europe and Asia, suggesting the possible introduction of these viruses from Eurasia, likely through wild bird migration. The fusion gene cleavage site motif for all LBM-associated isolates was 112RRQKR|F117, indicating that the viruses are virulent, while the isolates from wild waterfowl had the typical 112ERQER|L117 avirulent motif. This study demonstrates the circulation of virulent NDV strains in LBMs and has, for the first time, characterised NDV from wild birds in Zambia. The study further provides the first whole genomes of NDV sub-genotype VII.2 and genotype 1 from Zambia and stresses the importance of surveillance and molecular analysis for monitoring the circulation of NDV genotypes and viral evolution.
  • The impact of PA/I38 substitutions and PA polymorphisms on the susceptibility of zoonotic influenza A viruses to baloxavir.
    Keiichi Taniguchi; Takeshi Noshi; Shinya Omoto; Akihiko Sato; Takao Shishido; Keita Matsuno; Masatoshi Okamatsu; Scott Krauss; Richard J Webby; Yoshihiro Sakoda; Hiroshi Kida
    Archives of virology, 169, 2, 29, 29, 2024年01月12日, [国際誌]
    英語, 研究論文(学術雑誌), Genetic reassortment of avian, swine, and human influenza A viruses (IAVs) poses potential pandemic risks. Surveillance is important for influenza pandemic preparedness, but the susceptibility of zoonotic IAVs to the cap-dependent endonuclease inhibitor baloxavir acid (BXA) has not been thoroughly researched. Although an amino acid substitution at position 38 in the polymerase acidic protein (PA/I38) in seasonal IAVs reduces BXA susceptibility, PA polymorphisms at position 38 are rarely seen in zoonotic IAVs. Here, we examined the impact of PA/I38 substitutions on the BXA susceptibility of recombinant A(H5N1) viruses. PA mutants that harbored I38T, F, and M were 48.2-, 24.0-, and 15.5-fold less susceptible, respectively, to BXA than wild-type A(H5N1) but were susceptible to the neuraminidase inhibitor oseltamivir acid and the RNA polymerase inhibitor favipiravir. PA mutants exhibited significantly impaired replicative fitness in Madin-Darby canine kidney cells at 24 h postinfection. In addition, in order to investigate new genetic markers for BXA susceptibility, we screened geographically and temporally distinct IAVs isolated worldwide from birds and pigs. The results showed that BXA exhibited antiviral activity against avian and swine viruses with similar levels to seasonal isolates. All viruses tested in the study lacked the PA/I38 substitution and were susceptible to BXA. Isolates harboring amino acid polymorphisms at positions 20, 24, and 37, which have been implicated in the binding of BXA to the PA endonuclease domain, were also susceptible to BXA. These results suggest that monitoring of the PA/I38 substitution in animal-derived influenza viruses is important for preparedness against zoonotic influenza virus outbreaks.
  • H5亜型高病原性鳥インフルエンザウイルスの最新動向 1.最近の野生動物におけるH5亜型の高病原性鳥インフルエンザウイルスの感染状況について
    日尾野隆大; 日尾野隆大; 日尾野隆大; 日尾野隆大; 磯田典和; 磯田典和; 磯田典和; 磯田典和; 迫田義博; 迫田義博; 迫田義博; 迫田義博
    ウイルス, 74, 2, 107, 116, 2024年, [国内誌]
    日本語, H5 high pathogenicity avian influenza viruses, which emerged in Guangdong Province, China, in 1996, has now been persistently transmitted among various wild birds due to the "silent spreading" of the viruses among vaccinated poultry and domestic waterfowl. These viruses traveled long distances along with bird migration; therefore, the threat of H5 high pathogenicity avian influenza viruses is now a global issue. Furthermore, infection in wild mammals has become more prominent since 2020. The contamination of the wild bird population by the virus is considered to be an irreversible situation, and thus, the reduction of virus levels in the environment is an urgent issue to prevent further deterioration of the situation. This review will describe the history and current situations of influenza virus infection in wild birds and mammals, and discuss the research and countermeasures that are required to stop the damage caused by this virus.
  • Establishment of a superinfection exclusion method for pestivirus titration using a recombinant reporter pestiviruses
    Yume MIMURA; Takahiro HIONO; Loc Tan HUYNH; Saho OGINO; Maya KOBAYASHI; Norikazu ISODA; Yoshihiro SAKODA
    Journal of Veterinary Medical Science, 86, 4, 389, 395, Japanese Society of Veterinary Science, 2024年, [国内誌]
    英語, 研究論文(学術雑誌), Pestiviruses are classified into two biotypes based on their cytopathogenicity. As the majority of pestivirus field isolates are noncytopathogenic, their titration requires alternative methods rather than direct observation of cytopathogenic effects, such as immunostaining using specific antibodies or interference with cytopathogenic strains. However, these methods require microscopic observation to assess virus growth, which is time- and labor-intensive, especially when handling several samples. In this study, we developed a novel luciferase-based pestivirus titration method using the superinfection exclusion phenomenon with recombinant reporter pestiviruses that possessed an 11-amino-acid subunit derived from NanoLuc luciferase (HiBiT). In this method, swine kidney cells were inoculated with classical swine fever virus (CSFV) and superinfected with the reporter CSFV vGPE-/HiBiT 5 days postinoculation. Virus titer was determined based on virus growth measured in luminescence using the culture fluid 3 days after superinfection; the resultant virus titer was comparable to that obtained by immunoperoxidase staining. Furthermore, this method has proven to be applicable for the titration of border disease virus (BDV) by superinfection with both the homologous reporter BDV and heterologous reporter CSFV, suggesting that this novel virus titration method is a simple technique for automated virus detection based on the luciferase system.
  • Exploring Appropriate Strategies for Vaccination against Classical Swine Fever under a Dynamic Change in Antibody Titer in Sows after Starting Vaccination in a Japanese Farm Setting
    Makoto Ukita; Keisuke Kuwata; Eiji Tanaka; Ryota Matsuyama; Norikazu Isoda; Yoshihiro Sakoda; Takehisa Yamamoto; Kohei Makita
    Transboundary and Emerging Diseases, 2023, 1, 15, Hindawi Limited, 2023年11月30日
    研究論文(学術雑誌), After 26 years of absence in Japan, a classical swine fever (CSF) outbreak occurred at a domestic pig farm in 2018. Vaccination against the CSF virus with a live attenuated vaccine at pig farms was restarted in October 2019, which was 13 years after the 2006 ban on vaccination. An individual-based simulation model for CSF antibody dynamics was developed to determine an effective CSF vaccination strategy for pig populations. In creating a simulated pig herd, the optimal vaccination age of piglets and the effect of vaccinating piglets twice were evaluated. Additionally, the herd immunity was monitored every 6 months for 4 years after the start of vaccination, and the effects of intensive sow replacement policies were assessed. The simulation results indicated that the vaccination age should be delayed relative to the age used before the 2006 ban on vaccination and shifted earlier, from 8 weeks to 6 weeks, as time elapses. The simulations indicated a tradeoff in protection between the weaning period (i.e., maternally derived antibodies) and the fattening period (i.e., by vaccine-induced antibodies). Mixing sows with high and low antibody titers, particularly sows that received the first vaccination and those born after the start of vaccination, resulted in a high variation in antibody titer among pigs on the farm. This study also clarified the positive effect of intensive sow replacement strategies on shortening the period in which sows show diverse titers. Differences in sow replacement rates among farms and/or the time lag in starting vaccination in different prefectures result in heterogeneity in herd immunity in Japan; thus, herd immunity status should be examined at every farm using this simulation model.
  • Development of short hairpin RNA expression vectors targeting the internal ribosomal entry site of the classical swine fever virus genomic RNA.
    Riai Okamoto; Nobumasa Ito; Yutaro Ide; Bouchra Kitab; Yoshihiro Sakoda; Kyoko Tsukiyama-Kohara
    BMC biotechnology, 23, 1, 37, 37, 2023年09月08日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Classical swine fever (CSF) is a fatal contagious disease affecting pigs caused by classical swine fever virus (CSFV). The disease can be transmitted by pigs and wild boars, and it is difficult to prevent and control. To obtain necessary information to establish the CSFV resistant animals in a future study, we designed lentiviral vector-delivered short hairpin RNAs (shRNAs) targeting the conserved domain III of the internal ribosomal entry site (IRES) of the CSFV genomic RNA. RESULTS: First, we confirmed the effects of siRNAs on CSFV-IRES activity. We observed significant inhibition of CSFV-IRES activity by si42 (domain IIIa), si107 (domain IIIc), and si198 (domain IIIf) in SK-L cells and si56 (domain IIIb), si142 (domain IIId1) and si198 in HEK293 cells without affecting the amount of luciferase RNA. Next, we constructed lentiviral vectors expressing shRNA based on siRNA sequences. Treatment with shRNA-expressing lentivirus was examined at 7 and 14 days post infection in SK-L cells and HEK293 cells, and CSFV-IRES was significantly suppressed at 14 days (sh42) post infection in HEK293 cells without significant cytotoxicity. Next, we examined the silencing effect of siRNA on CSFV replicon RNA and observed a significant effect by si198 after 2 days of treatment and by shRNA-expressing lentivirus (sh56, sh142, and sh198) infection after 14 days of treatment. Treatment of sh198-expressing lentivirus significantly suppressed CSFV infection at 3 days after infection. CONCLUSION: The IRES targeting sh198 expressing lentivirus vector can be a candidate tool for CSFV infection control.
  • Detection of H5N1 High Pathogenicity Avian Influenza Viruses in Four Raptors and Two Geese in Japan in the Fall of 2022.
    Kei Nabeshima; Yoshihiro Takadate; Kosuke Soda; Takahiro Hiono; Norikazu Isoda; Yoshihiro Sakoda; Junki Mine; Kohtaro Miyazawa; Manabu Onuma; Yuko Uchida
    Viruses, 15, 9, 2023年09月01日, [国際誌]
    英語, 研究論文(学術雑誌), In the fall of 2022, high pathogenicity avian influenza viruses (HPAIVs) were detected from raptors and geese in Japan, a month earlier than in past years, indicating a shift in detection patterns. In this study, we conducted a phylogenetic analysis on H5N1 HPAIVs detected from six wild birds during the 2022/2023 season to determine their genetic origins. Our findings revealed that these HPAIVs belong to the G2 group within clade 2.3.4.4b, with all isolates classified into three subgroups: G2b, G2d, and G2c. The genetic background of the G2b virus (a peregrine falcon-derived strain) and G2d viruses (two raptors and two geese-derived strains) were the same as those detected in Japan in the 2021/2022 season. Since no HPAI cases were reported in Japan during the summer of 2022, it is probable that migratory birds reintroduced the G2b and G2d viruses. Conversely, the G2c virus (a raptor-derived strain) was first recognized in Japan in the fall of 2022. This strain might share a common ancestor with HPAIVs from Asia and West Siberia observed in the 2021/2022 season. The early migration of waterfowl to Japan in the fall of 2022 could have facilitated the early invasion of HPAIVs.
  • Generation and Efficacy of Two Chimeric Viruses Derived from GPE− Vaccine Strain as Classical Swine Fever Vaccine Candidates
    Loc Tan Huynh; Norikazu Isoda; Lim Yik Hew; Saho Ogino; Yume Mimura; Maya Kobayashi; Taksoo Kim; Tatsuya Nishi; Katsuhiko Fukai; Takahiro Hiono; Yoshihiro Sakoda
    Viruses, 15, 7, 1587, 1587, MDPI AG, 2023年07月20日, [国際誌]
    英語, 研究論文(学術雑誌), A previous study proved that vGPE− mainly maintains the properties of classical swine fever (CSF) virus, which is comparable to the GPE− vaccine seed and is a potentially valuable backbone for developing a CSF marker vaccine. Chimeric viruses were constructed based on an infectious cDNA clone derived from the live attenuated GPE− vaccine strain as novel CSF vaccine candidates that potentially meet the concept of differentiating infected from vaccinated animals (DIVA) by substituting the glycoprotein Erns of the GPE− vaccine strain with the corresponding region of non-CSF pestiviruses, either pronghorn antelope pestivirus (PAPeV) or Phocoena pestivirus (PhoPeV). High viral growth and genetic stability after serial passages of the chimeric viruses, namely vGPE−/PAPeV Erns and vGPE−/PhoPeV Erns, were confirmed in vitro. In vivo investigation revealed that two chimeric viruses had comparable immunogenicity and safety profiles to the vGPE− vaccine strain. Vaccination at a dose of 104.0 TCID50 with either vGPE−/PAPeV Erns or vGPE−/PhoPeV Erns conferred complete protection for pigs against the CSF virus challenge in the early stage of immunization. In conclusion, the characteristics of vGPE−/PAPeV Erns and vGPE−/PhoPeV Erns affirmed their properties, as the vGPE− vaccine strain, positioning them as ideal candidates for future development of a CSF marker vaccine.
  • Surveillance and Phylogenetic Characterisation of Avian Influenza Viruses Isolated from Wild Waterfowl in Zambia in 2015, 2020, and 2021
    Annie Kalonda; Ngonda Saasa; Masahiro Kajihara; Naganori Nao; Ladislav Moonga; Joseph Ndebe; Akina Mori-Kajihara; Andrew Nalishuwa Mukubesa; Mulemba Samutela; Samuel Munjita; Yoshihiro Sakoda; Hirofumi Sawa; Ayato Takada; Edgar Simulundu
    Transboundary and Emerging Diseases, 2023, 1, 16, Hindawi Limited, 2023年03月01日
    研究論文(学術雑誌), In recent years, the southern African region has experienced repeated incursions of highly pathogenic avian influenza viruses (HPAIVs), with wild migratory birds being implicated in the spread. To understand the profile of avian influenza viruses (AIVs) circulating in Zambia, we surveyed wild waterfowl for AIVs and phylogenetically characterised the isolates detected in 2015, 2020, and 2021. A total of 2,851 faecal samples of wild waterfowl were collected from Lochinvar National Park in the Southern Province of Zambia. During the study period, 85 (3.0%) low pathogenicity AIVs belonging to various subtypes were isolated, with H2N9, H8N4, and H10N8 being reported for the first time in avian species in Africa. The majority of the isolates were detected from glossy ibis (order Pelecaniformes) making it the first report of AIV from these birds in Zambia. Phylogenetic analysis of all eight gene segments of the 30 full genomes obtained in this study revealed that all the isolates belonged to the Eurasian lineage with their closest relatives being viruses isolated from wild and/or domestic birds in Bangladesh, Belgium, Egypt, Georgia, Mongolia, the Netherlands, and South Africa. Additionally, the Zambian viruses were grouped into distinct clusters based on the year of isolation. While no notifiable AIVs of the H5 or H7 subtypes were detected in wild birds in Zambia, viral internal protein genes of some viruses were closely related to H7 low pathogenicity AIVs. This study shows that periodically, a considerable diversity of AIV subtypes are introduced into the Zambian ecosystem by wild migratory waterfowl. The findings highlight the importance of continuous surveillance and monitoring of AIVs in wild waterfowl, including birds traditionally not considered to be major AIV reservoirs, for a better understanding of the eco-epidemiology and evolutionary dynamics of AIVs in Africa.
  • Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication.
    Yuta Tsukamoto; Takahiro Hiono; Shintaro Yamada; Keita Matsuno; Aileen Faist; Tobias Claff; Jianyu Hou; Vigneshwaran Namasivayam; Anja Vom Hemdt; Satoko Sugimoto; Jin Ying Ng; Maria H Christensen; Yonas M Tesfamariam; Steven Wolter; Stefan Juranek; Thomas Zillinger; Stefan Bauer; Takatsugu Hirokawa; Florian I Schmidt; Georg Kochs; Masayuki Shimojima; Yi-Shuian Huang; Andreas Pichlmair; Beate M Kümmerer; Yoshihiro Sakoda; Martin Schlee; Linda Brunotte; Christa E Müller; Manabu Igarashi; Hiroki Kato
    Science (New York, N.Y.), 379, 6632, 586, 591, 2023年02月10日, [国際誌]
    英語, 研究論文(学術雑誌), Orthomyxo- and bunyaviruses steal the 5' cap portion of host RNAs to prime their own transcription in a process called "cap snatching." We report that RNA modification of the cap portion by host 2'-O-ribose methyltransferase 1 (MTr1) is essential for the initiation of influenza A and B virus replication, but not for other cap-snatching viruses. We identified with in silico compound screening and functional analysis a derivative of a natural product from Streptomyces, called trifluoromethyl-tubercidin (TFMT), that inhibits MTr1 through interaction at its S-adenosyl-l-methionine binding pocket to restrict influenza virus replication. Mechanistically, TFMT impairs the association of host cap RNAs with the viral polymerase basic protein 2 subunit in human lung explants and in vivo in mice. TFMT acts synergistically with approved anti-influenza drugs.
  • Genetic, Antigenic, and Pathobiological Characterization of H9 and H6 Low Pathogenicity Avian Influenza Viruses Isolated in Vietnam from 2014 to 2018.
    Kien Trung Le; Lam Thanh Nguyen; Loc Tan Huynh; Duc-Huy Chu; Long Van Nguyen; Tien Ngoc Nguyen; Tien Ngoc Tien; Keita Matsuno; Masatoshi Okamatsu; Takahiro Hiono; Norikazu Isoda; Yoshihiro Sakoda
    Microorganisms, 11, 2, 2023年01月18日, [国際誌]
    英語, 研究論文(学術雑誌), The H9 and H6 subtypes of low pathogenicity avian influenza viruses (LPAIVs) cause substantial economic losses in poultry worldwide, including Vietnam. Herein, we characterized Vietnamese H9 and H6 LPAIVs to facilitate the control of avian influenza. The space-time representative viruses of each subtype were selected based on active surveillance from 2014 to 2018 in Vietnam. Phylogenetic analysis using hemagglutinin genes revealed that 54 H9 and 48 H6 Vietnamese LPAIVs were classified into the sublineages Y280/BJ94 and Group II, respectively. Gene constellation analysis indicated that 6 and 19 genotypes of the H9 and H6 subtypes, respectively, belonged to the representative viruses. The Vietnamese viruses are genetically related to the previous isolates and those in neighboring countries, indicating their circulation in poultry after being introduced into Vietnam. The antigenicity of these subtypes was different from that of viruses isolated from wild birds. Antigenicity was more conserved in the H9 viruses than in the H6 viruses. Furthermore, a representative H9 LPAIV exhibited systemic replication in chickens, which was enhanced by coinfection with avian pathogenic Escherichia coli O2. Although H9 and H6 were classified as LPAIVs, their characterization indicated that their silent spread might significantly affect the poultry industry.
  • Susceptibility of common dabbling and diving duck species to clade 2.3.2.1 H5N1 high pathogenicity avian influenza virus: an experimental infection study
    Kosuke SODA; Yukiko TOMIOKA; Tatsufumi USUI; Hiroichi OZAKI; Hiroshi ITO; Yasuko NAGAI; Naoki YAMAMOTO; Masatoshi OKAMATSU; Norikazu ISODA; Masahiro KAJIHARA; Yoshihiro SAKODA; Ayato TAKADA; Toshihiro ITO
    Journal of Veterinary Medical Science, 85, 9, 942, 949, Japanese Society of Veterinary Science, 2023年, [国内誌]
    英語, 研究論文(学術雑誌), In the winter of 2010-2011, Japan experienced a large outbreak of infections caused by clade 2.3.2.1 H5N1 high pathogenicity avian influenza viruses (HPAIVs) in wild birds. Interestingly, many tufted ducks (Aythya fuligula), which are migratory diving ducks, succumbed to the infection, whereas only one infection case was reported in migratory dabbling duck species, the major natural hosts of the influenza A virus, during the outbreak. To assess whether the susceptibility of each duck species to HPAIVs was correlated with the number of cases, tufted duck and dabbling duck species (Eurasian wigeon, Mareca penelope; mallard, Anas platyrhynchos; Northern pintail, Anas acuta) were intranasally inoculated with A/Mandarin duck/Miyazaki/22M807-1/2011 (H5N1), an index clade 2.3.2.1 virus previously used for experimental infection studies in various bird species. All ducks observed for 10 days post-inoculation (dpi) mostly shed the virus via the oral route and survived. The tufted ducks shed a higher titer of the virus than the other dabbling duck species, and one of them showed apparent neurological symptoms after 7 dpi, which were accompanied by eye lesions. No clinical symptoms were observed in the dabbling ducks, although systemic infection and viremia were observed in some of them sacrificed at 3 dpi. These results suggest that the susceptibility of clade 2.3.2.1 HPAIVs might differ by duck species.
  • 豚熱ワクチン接種適齢期の推定モデルの構築
    桑田 桂輔; 浮田 真琴; 加藤 智; 國永 尚稔; 田中 英次; 迫田 義博; 蒔田 浩平
    日本獣医師会雑誌, 76, 11, e274, e282, (公社)日本獣医師会, 2023年
    日本語
  • Virological, pathological, and glycovirological investigations of an Ezo red fox and a tanuki naturally infected with H5N1 highly pathogenic avian influenza viruses in Hokkaido, Japan
    Takahiro Hiono; Daiki Kobayashi; Atsushi Kobayashi; Tamami Suzuki; Yuki Satake; Rio Harada; Keita Matsuno; Mariko Sashika; Hinako Ban; Maya Kobayashi; Keisuke Aoshima; Fumihito Takaya; Hiroko Fujita; Norikazu Isoda; Takashi Kimura; Yoshihiro Sakoda
    Virology, 578, 35, 44, 2023年01月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), In winter/spring 2021-2022, high pathogenicity avian influenza viruses (HPAIVs) that are genetically closely related to each other were detected worldwide. In a public garden in Sapporo, Hokkaido, Japan, a crow die-off by HPAIV infection occurred from March 29 to May 18, 2022. During the event, H5N1 HPAIVs were isolated from an Ezo red fox (Vulpes vulpes schrencki) and a tanuki (Nyctereutes procyonoides albus) found in the same garden. The fox showed viral meningoencephalitis and moderate virus replication in the upper respiratory tract, whereas the tanuki showed viral conjunctivitis and secondary bacterial infection in the eyes accompanied with visceral larva migrans. Viruses isolated from the fox and the tanuki were genetically closely related to those isolated from crows in the same garden. Various α2-3 sialosides were found in the respiratory tracts of these canid mammals, consistent with HPAIV infections in these animals. This study highlighted the importance of monitoring HPAIV infections in wild carnivore mammals to detect the potential virus spreading in nature.
  • Experimental and natural infections of white-tailed sea eagles (Haliaeetus albicilla) with high pathogenicity avian influenza virus of H5 subtype
    Yoshikazu Fujimoto; Kohei Ogasawara; Norikazu Isoda; Hitoshi Hatai; Kosuke Okuya; Yukiko Watanabe; Ayato Takada; Yoshihiro Sakoda; Keisuke Saito; Makoto Ozawa
    Frontiers in Microbiology, 13, Frontiers Media SA, 2022年10月03日
    研究論文(学術雑誌), White-tailed sea eagle (Haliaeetus albicilla), a regionally rare species of raptor, is threatened in several countries. To assess the risk of H5 high pathogenicity avian influenza (HPAI) viral infection in rare bird species, we performed experimental infections with a GS/GD96-lineage H5N6 HPAI virus of clade 2.3.4.4e in white-tailed sea eagles. Additionally, during the winter of 2020–2021 in Japan, we accidentally encountered a white-tailed sea eagle that had a fatal outcome due to natural infection with a GS/GD96-lineage H5N8 HPAI virus of clade 2.3.4.4b, allowing us to compare experimental and natural infections in the same rare raptor species. Our experiments demonstrated the susceptibility of white-tailed sea eagles to the GS/GD96-lineage H5 HPAI virus with efficient replication in systemic organs. The potential for the viruses to spread within the white-tailed sea eagle population through indirect transmission was also confirmed. Comprehensive comparisons of both viral distribution and histopathological observations between experimentally and naturally infected white-tailed sea eagles imply that viral replication in the brain is responsible for the disease severity and mortality in this species. These findings provide novel insights into the risk assessment of H5 HPAI viral infection in white-tailed sea eagles, proper diagnostic procedures, potential risks to artificially fed eagle populations and persons handling superficially healthy eagles, potential impact of intragastric infection on eagle outcomes, and possibility of severity of the disease being attributed to viral replication in the brain.
  • Molecular characterisation of a novel avian rotavirus A strain detected from a gull species (Larus sp.).
    Yuji Fujii; Tatsunori Masatani; Shoko Nishiyama; Misuzu Okajima; Fumiki Izumi; Katsunori Okazaki; Yoshihiro Sakoda; Ayato Takada; Makoto Ozawa; Makoto Sugiyama; Naoto Ito
    The Journal of general virology, 103, 10, 2022年10月, [国際誌]
    英語, 研究論文(学術雑誌), A recent study demonstrated the possibility that migratory birds are responsible for the global spread of avian rotavirus A (RVA). However, little is known about what types of RVAs are retained in migratory birds. In this study, to obtain information on RVA strains in migratory birds, we characterised an RVA strain, Ho374, that was detected in a faecal sample from a gull species (Larus sp.). Genetic analysis revealed that all 11 genes of this strain were classified as new genotypes (G28-P[39]-I21-R14-C14-M13-A24-N14-T16-E21-H16). This clearly indicates that the genetic diversity of avian RVAs is greater than previously recognised. Our findings highlight the need for investigations of RVA strains retained in migratory birds, including gulls.
  • Detection of New H5N1 High Pathogenicity Avian Influenza Viruses in Winter 2021-2022 in the Far East, Which Are Genetically Close to Those in Europe.
    Norikazu Isoda; Manabu Onuma; Takahiro Hiono; Ivan Sobolev; Hew Yik Lim; Kei Nabeshima; Hisako Honjyo; Misako Yokoyama; Alexander Shestopalov; Yoshihiro Sakoda
    Viruses, 14, 10, 2022年09月30日, [国際誌]
    英語, 研究論文(学術雑誌), Many high pathogenicity avian influenza (HPAI) cases in wild birds due to H5N1 HPAI virus (HPAIV) infection were reported in northern Japan in the winter of 2021-2022. To investigate the epidemiology of HPAIVs brought to Japan from surrounding areas, a genetic analysis of H5 HPAIVs isolated in northern Japan was performed, and the pathogenicity of the HPAIV in chickens was assessed by experimental infection. Based on the genetic analysis of the hemagglutinin gene, pathogenic viruses detected in northern Japan as well as one in Sakhalin, the eastern part of Russia, were classified into the same subgroup as viruses prevalent in Europe in the same season but distinct from those circulating in Asia in winter 2020-2021. High identities of all eight segment sequences of A/crow/Hokkaido/0103B065/2022 (H5N1) (Crow/Hok), the representative isolates in northern Japan in 2022, to European isolates in the same season could also certify the unlikeliness of causing gene reassortment between H5 HPAIVs and viruses locally circulating in Asia. According to intranasal challenge results in six-week-old chickens, 50% of the chicken-lethal dose of Crow/Hok was calculated as 104.5 times of the 50% egg-infectious dose. These results demonstrated that the currently prevalent H5 HPAIVs could spread widely from certain origins throughout the Eurasian continent, including Europe and the Far East, and implied a possibility that contagious viruses are gathered in lakes in the northern territory via bird migration. Active monitoring of wild birds at the global level is essential to estimate the geographical source and spread dynamics of HPAIVs.
  • Identification of cap-dependent endonuclease inhibitors with broad-spectrum activity against bunyaviruses.
    Shinsuke Toba; Akihiko Sato; Makoto Kawai; Yoshiyuki Taoda; Yuto Unoh; Shinji Kusakabe; Haruaki Nobori; Shota Uehara; Kentaro Uemura; Keiichi Taniguchi; Masanori Kobayashi; Takeshi Noshi; Ryu Yoshida; Akira Naito; Takao Shishido; Junki Maruyama; Slobodan Paessler; Michael J Carr; William W Hall; Kumiko Yoshimatsu; Jiro Arikawa; Keita Matsuno; Yoshihiro Sakoda; Michihito Sasaki; Yasuko Orba; Hirofumi Sawa; Hiroshi Kida
    Proceedings of the National Academy of Sciences of the United States of America, 119, 36, e2206104119, 2022年09月06日, [国際誌]
    英語, 研究論文(学術雑誌), Viral hemorrhagic fevers caused by members of the order Bunyavirales comprise endemic and emerging human infections that are significant public health concerns. Despite the disease severity, there are few therapeutic options available, and therefore effective antiviral drugs are urgently needed to reduce disease burdens. Bunyaviruses, like influenza viruses (IFVs), possess a cap-dependent endonuclease (CEN) that mediates the critical cap-snatching step of viral RNA transcription. We screened compounds from our CEN inhibitor (CENi) library and identified specific structural compounds that are 100 to 1,000 times more active in vitro than ribavirin against bunyaviruses, including Lassa virus, lymphocytic choriomeningitis virus (LCMV), and Junin virus. To investigate their inhibitory mechanism of action, drug-resistant viruses were selected in culture. Whole-genome sequencing revealed that amino acid substitutions in the CEN region of drug-resistant viruses were located in similar positions as those of the CEN α3-helix loop of IFVs derived under drug selection. Thus, our studies suggest that CENi compounds inhibit both bunyavirus and IFV replication in a mechanistically similar manner. Structural analysis revealed that the side chain of the carboxyl group at the seventh position of the main structure of the compound was essential for the high antiviral activity against bunyaviruses. In LCMV-infected mice, the compounds significantly decreased blood viral load, suppressed symptoms such as thrombocytopenia and hepatic dysfunction, and improved survival rates. These data suggest a potential broad-spectrum clinical utility of CENis for the treatment of both severe influenza and hemorrhagic diseases caused by bunyaviruses.
  • Risk profile of low pathogenicity avian influenza virus infections in farms in southern Vietnam.
    Kien Trung LE; Norikazu Isoda; Lam Thanh Nguyen; Duc-Huy Chu; Long Van Nguyen; Minh Quang Phan; Diep Thi Nguyen; Tien Ngoc Nguyen; Tien Ngoc Tien; Tung Thanh LE; Takahiro Hiono; Keita Matsuno; Masatoshi Okamatsu; Yoshihiro Sakoda
    The Journal of veterinary medical science, 84, 6, 860, 868, 2022年05月13日, [国内誌]
    英語, 研究論文(学術雑誌), The impact of low pathogenicity avian influenza (LPAI) has been confirmed mainly in farms. Unlike apparent losses caused by the high pathogenicity avian influenza (HPAI), the LPAI impact has been hardly evaluated due to underestimating its spread and damage. In 2019, a questionnaire study was conducted in southern Vietnam to identify the specific risk factors of LPAI virus (LPAIV) circulation and to find associations between husbandry activities and LPAI prevalence. A multilevel regression analysis indicated that keeping Muscovy ducks during farming contributed to LPAIV positivity [Odds ratio=208.2 (95% confidence interval: 13.4-1.1×104)]. In cluster analysis, farmers willing to report avian influenza (AI) events and who agreed with the local AI control policy had a slightly lower risk for LPAIV infection although there was no significance in the correlation between farmer characteristics and LPAI occurrence. These findings indicated that keeping Muscovy ducks without appropriate countermeasures might increase the risk of LPAIV infection. Furthermore, specific control measures at the local level are effective for LPAIV circulation, and the improvement of knowledge about biosecurity and attitude contributes to reducing LPAI damage.
  • Characterization of host factors associated with the internal ribosomal entry sites of foot-and-mouth disease and classical swine fever viruses.
    Yutaro Ide; Bouchra Kitab; Nobumasa Ito; Riai Okamoto; Yui Tamura; Takafumi Matsui; Yoshihiro Sakoda; Kyoko Tsukiyama-Kohara
    Scientific reports, 12, 1, 6709, 6709, 2022年04月25日, [国際誌]
    英語, 研究論文(学術雑誌), Foot-and-mouth disease virus (FMDV) and classical swine fever virus (CSFV) possess positive-sense single-stranded RNA genomes and an internal ribosomal entry site (IRES) element within their 5'-untranslated regions. To investigate the common host factors associated with these IRESs, we established cell lines expressing a bicistronic luciferase reporter plasmid containing an FMDV-IRES or CSFV-IRES element between the Renilla and firefly luciferase genes. First, we treated FMDV-IRES cells with the French maritime pine extract, Pycnogenol (PYC), and examined its suppressive effect on FMDV-IRES activity, as PYC has been reported to have antiviral properties. Next, we performed microarray analysis to identify the host factors that modified their expression upon treatment with PYC, and confirmed their function using specific siRNAs. We found that polycystic kidney disease 1-like 3 (PKD1L3) and ubiquitin-specific peptidase 31 (USP31) were associated with FMDV-IRES activity. Moreover, silencing of these factors significantly suppressed CSFV-IRES activity. Thus, PKD1L3 and USP31 are host factors associated with the functions of FMDV- and CSFV-IRES elements.
  • Turkeys possess diverse Siaα2-3Gal glycans that facilitate their dual susceptibility to avian influenza viruses isolated from ducks and chickens.
    Daiki Kobayashi; Takahiro Hiono; Osamu Ichii; Shoko Nishihara; Sayaka Takase-Yoden; Kazuo Yamamoto; Hiroto Kawashima; Norikazu Isoda; Yoshihiro Sakoda
    Virus research, 315, 198771, 198771, 2022年04月14日, [国際誌]
    英語, 研究論文(学術雑誌), Avian influenza viruses (AIVs) circulating in wild ducks are rarely transmitted directly to chickens. Previous studies demonstrated that chickens possess fucosylated and/or sulfated α2,3 sialosides on their tracheal epithelia, whereas intestinal epithelia of ducks express canonical α2,3 sialosides. Turkeys, the third major poultry species in the world, are known to show broad susceptibility to various avian influenza viruses. To elucidate the molecular basis of the broad susceptibility of turkeys to duck and chicken AIVs, we characterized various receptors for AIVs on their tissues. The experimental infection of turkeys demonstrated their dual susceptibility to duck and chicken AIVs. Further, comprehensive histochemical analyses using lectins, anti-glycan antibodies, and recombinant hemagglutinins, combined with glycosidase digestions, identified the presence of fucosylated and/or sulfated in addition to canonical α2,3 sialosides on their respiratory epithelia. The receptor distributions in turkeys were consistent with their dual susceptibility to duck and chicken AIVs. Also, our findings suggested the potential roles of turkeys in interspecies transmission of AIVs from ducks to chickens.
  • Strategies for fighting pandemic virus infections: Integration of virology and drug delivery.
    Takashi Nakamura; Norikazu Isoda; Yoshihiro Sakoda; Hideyoshi Harashima
    Journal of controlled release : official journal of the Controlled Release Society, 343, 361, 378, 2022年02月03日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Respiratory viruses have sometimes resulted in worldwide pandemics, with the influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) being major participants. Long-term efforts have made it possible to control the influenza virus, but seasonal influenza continues to take many lives each year, and a pandemic influenza virus sometimes emerges. Although vaccines for coronavirus disease 2019 (COVID-19) have been developed, we are not yet able to coexist with the SARS-CoV-2. To overcome such viruses, it is necessary to obtain knowledge about international surveillance systems, virology, ecology and to determine that immune responses are effective. The information must then be transferred to drugs. Delivery systems would be expected to contribute to the rational development of drugs. In this review, virologist and drug delivery system (DDS) researchers discuss drug delivery strategies, especially the use of lipid-based nanocarriers, for fighting to respiratory virus infections.
  • Antiviral Effects of 5-Aminolevulinic Acid Phosphate against Classical Swine Fever Virus: In Vitro and In Vivo Evaluation.
    Shizuka Hirose; Norikazu Isoda; Loc Tan Huynh; Taksoo Kim; Keiichiro Yoshimoto; Tohru Tanaka; Kenjiro Inui; Takahiro Hiono; Yoshihiro Sakoda
    Pathogens (Basel, Switzerland), 11, 2, 2022年01月27日, [国際誌]
    英語, 研究論文(学術雑誌), The inhibitory effects of 5-aminolevulinic acid phosphate (5-ALA), an important amino acid for energy production in the host, against viral infections were previously reported. Here, the antiviral effects of 5-ALA against classical swine fever virus (CSFV) belonging to the genus Pestivirus in the Flaviviridae family and its possible mechanisms were investigated. CSFV replication was suppressed in swine cells supplemented with 5-ALA or its metabolite, protoporphyrin IX (PPIX). The infectivity titer of CSFV was decreased after mixing with PPIX extracellularly. In addition, the activities of the replication cycle were decreased in the presence of PPIX based on the CSFV replicon assay. These results showed that PPIX exerted antiviral effects by inactivating virus particles and inhibiting the replication cycle. To evaluate the in vivo efficacy of 5-ALA, pigs were supplemented daily with 5-ALA for 1 week before virus inoculation and then inoculated with a virulent CSFV strain at the 107.0 50% tissue culture infectious dose. The clinical scores of the supplemented group were significantly lower than those of the nonsupplemented group, whereas the virus growth was not. Taken together, 5-ALA showed antiviral effects against CSFV in vitro, and PPIX played a key role by inactivating virus particles extracellularly and inhibiting the replication cycle intracellularly.
  • Susceptibility of herons (family: Ardeidae) to clade 2.3.2.1 H5N1 subtype high pathogenicity avian influenza virus.
    Kosuke Soda; Yukiko Tomioka; Tatsufumi Usui; Yukiko Uno; Yasuko Nagai; Hiroshi Ito; Takahiro Hiono; Tomokazu Tamura; Masatoshi Okamatsu; Masahiro Kajihara; Naganori Nao; Yoshihiro Sakoda; Ayato Takada; Toshihiro Ito
    Avian pathology : journal of the W.V.P.A, 51, 2, 1, 8, 2022年01月25日, [国際誌]
    英語, 研究論文(学術雑誌), The pathogenicity of the H5 subtype high pathogenicity avian influenza viruses (HPAIVs) in Ardeidae bird species has not been investigated yet, despite the increasing infections reported. Therefore, the present study aimed to examine the susceptibility of the Ardeidae species, which had already been reported to be susceptible to HPAIVs, to a clade 2.3.2.1 H5N1 HPAIV. Juvenile herons (four grey herons, one intermediate egret, two little egrets, and three black-crowned night herons) were intranasally inoculated with 106 50% egg infectious dose of the virus and observed for 10 days. Two of the four grey herons showed lethargy and conjunctivitis; among them, one died at 6 days post-inoculation (dpi). The viruses were transmitted to the other two cohoused naïve grey herons. Some little egrets and black-crowned night herons showing neurological disorders died at 4-5 dpi; these birds mainly shed the virus via the oral route. The viruses predominantly replicated in the brains of birds that died of infection. Seroconversion was observed in most surviving birds, except some black-crowned night herons. These results demonstrate that most Ardeidae species are susceptible to H5 HPAIVs, sometimes with lethal effects. Herons are mostly colonial and often share habitats with Anseriformes, natural hosts of influenza A viruses; therefore, the risks of cluster infection and contribution to viral dissemination should be continuously evaluated. RESEARCH HIGHLIGHTSClade 2.3.2.1 H5N1 HPAIV causes lethal infections in Ardeidae sp.Viruses are transmitted among grey herons.Some herons with HPAIV showed conjunctivitis or neurological symptoms.HPAIV systemically replicated in herons tissues.
  • N-glycolylneuraminic acid binding of avian and equine H7 influenza A viruses.
    Cindy M Spruit; Xueyong Zhu; Ilhan Tomris; María Ríos Carrasco; Alvin X Han; Frederik Broszeit; Roosmarijn van der Woude; Kim M Bouwman; Michel M T Luu; Keita Matsuno; Yoshihiro Sakoda; Colin A Russell; Ian A Wilson; Geert-Jan Boons; Robert P de Vries
    Journal of virology, 96, 5, jvi0212021, 2022年01月19日, [国際誌]
    英語, 研究論文(学術雑誌), Influenza A viruses (IAV) initiate infection by binding to glycans with terminal sialic acids on the cell surface. Hosts of IAV variably express two major forms of sialic acid, N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc). NeuGc is produced in most mammals including horses and pigs, but is absent in humans, ferrets, and birds. The only known naturally occurring IAVs that exclusively bind NeuGc are extinct highly pathogenic equine H7N7 viruses. We determined the crystal structure of a representative equine H7 hemagglutinin (HA) in complex with NeuGc and observed high similarity in the receptor-binding domain with an avian H7 HA. To determine the molecular basis for NeuAc and NeuGc specificity, we performed systematic mutational analyses, based on the structural insights, on two distant avian H7 HAs and an H15 HA. We found that mutation A135E is key for binding α2,3-linked NeuGc but does not abolish NeuAc binding. Additional mutations S128T, I130V, T189A, and K193R converted the specificity from NeuAc to NeuGc. We investigated the residues at positions 128, 130, 135, 189, and 193 in a phylogenetic analysis of avian and equine H7 HAs. This revealed a clear distinction between equine and avian residues. The highest variability was observed at key position 135, of which only the equine glutamic acid led to NeuGc binding. These results demonstrate that genetically distinct H7 and H15 HAs can be switched from NeuAc to NeuGc binding and vice versa after introduction of several mutations, providing insights into the adaptation of H7 viruses to NeuGc receptors. (250 words) Importance Influenza A viruses cause millions of cases of severe illness and deaths annually. To initiate infection and replicate, the virus first needs to bind to a structure on the cell surface, like a key fitting in a lock. For influenza A viruses, these 'keys' (receptors) on the cell surface are chains of sugar molecules (glycans). The terminal sugar on these glycans is often either N-acetylneuraminic acid (NeuAc) or N-glycolylneuraminic acid (NeuGc). Most influenza A viruses bind NeuAc, but a small minority binds NeuGc. NeuGc is present in species like horses, pigs, and mice, but not in humans, ferrets, and birds. Here, we investigated the molecular determinants of NeuGc specificity and the origin of viruses that bind NeuGc.
  • Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against H5 Highly Pathogenic Avian Influenza Virus Infection.
    Keiichi Taniguchi; Yoshinori Ando; Masanori Kobayashi; Shinsuke Toba; Haruaki Nobori; Takao Sanaki; Takeshi Noshi; Makoto Kawai; Ryu Yoshida; Akihiko Sato; Takao Shishido; Akira Naito; Keita Matsuno; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida
    Viruses, 14, 1, 2022年01月08日, [国際誌]
    英語, 研究論文(学術雑誌), Human infections caused by the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threaten public health. The susceptibility of HPAIVs to baloxavir acid (BXA), a new class of inhibitors for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but it has not yet been fully characterized. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants, was assessed in vitro. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested in comparison with seasonal and other zoonotic strains. Compared with oseltamivir phosphate (OSP), BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate, the A/Hong Kong/483/1997 strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, thereby preventing acute lung inflammation and reducing mortality. Furthermore, compared with BXM or OSP monotherapy, combination treatments with BXM and OSP using a 48-h delayed treatment model showed a more potent effect on viral replication in the organs, accompanied by improved survival. In conclusion, BXM has a potent antiviral efficacy against H5 HPAIV infections.
  • Endemic infections of bovine viral diarrhea virus genotypes 1b and 2a isolated from cattle in Japan between 2014 and 2020.
    Asami Nishimori; Shizuka Hirose; Saho Ogino; Kiyohiko Andoh; Norikazu Isoda; Yoshihiro Sakoda
    The Journal of veterinary medical science, 84, 2, 228, 232, 2021年12月14日, [最終著者, 責任著者], [国内誌]
    英語, 研究論文(学術雑誌), Bovine viral diarrhea virus (BVDV) is a causative agent of bovine viral diarrhea. In Japan, a previous study reported that subgenotype 1b viruses were predominant until 2014. Because there is little information regarding the recent epidemiological status of BVDV circulating in Japan, we performed genetic characterization of 909 BVDV isolates obtained between 2014 and 2020. We found that 657 and 252 isolates were classified as BVDV-1 and BVDV-2, respectively, and that they were further subdivided into 1a (35 isolates, 3.9%), 1b (588, 64.7%), 1c (34, 3.7%), and 2a (252, 27.7%). Phylogenetic analysis using entire E2 coding sequence revealed that a major domestic cluster in Japan among BVDV-1b and 2a viruses were unchanged from a previous study conducted from 2006 to 2014. These results provide updated information concerning the epidemic strain of BVDV in Japan, which would be helpful for appropriate vaccine selection.
  • Dynamics of invasion and dissemination of H5N6 highly pathogenic avian influenza viruses in 2016-2017 winter in Japan.
    Kosuke Soda; Hiroichi Ozaki; Hiroshi Ito; Tatsufumi Usui; Masatoshi Okamatsu; Keita Matsuno; Yoshihiro Sakoda; Tsuyoshi Yamaguchi; Toshihiro Ito
    The Journal of veterinary medical science, 83, 12, 1891, 1898, 2021年12月02日, [国内誌]
    英語, 研究論文(学術雑誌), Large highly pathogenic avian influenza (HPAI) outbreaks caused by clade 2.3.4.4e H5N6 viruses occurred in Japan during the 2016-2017 winter. To date, several reports regarding these outbreaks have been published, however a comprehensive study including geographical and time course validations has not been performed. Herein, 58 Japanese HPAI virus (HPAIV) isolates from the 2016-2017 season were added for phylogenetic analyses and the antigenic relationships among the causal viruses were elucidated. The locations where HPAIVs were found in the early phase of the outbreaks were clustered into three regions. Genotypes C1, C5, and C6-8 HPAIVs were found in specific areas. Two strains had phylogenetically distinct hemagglutinin (HA) and non-structural (NS) genes from other previously identified strains, respectively. The estimated latest divergence date between the viral genotypes suggests that genetic reassortment occurred in bird populations before their winter migration to Japan. Antigenic differences in 2016-2017 HPAIVs were not observed, suggesting that antibody pressure in the birds did not contribute to the selection of HPAIV genotypes. In the late phase, the majority of HPAI cases in wild birds occurred south of the lake freezing line. At the end of the outbreak, HPAI re-occurred in East coast region, which may be due to the spring migration route of Anas bird species. These trends were similar to those observed in the 2010-2011 outbreaks, suggesting there is a typical pattern of seeding and dissemination of HPAIV in Japan.
  • A systematic approach to illuminate a new hot spot of avian influenza virus circulation in South Vietnam, 2016-2017.
    Kien Trung Le; Mark A Stevenson; Norikazu Isoda; Lam Thanh Nguyen; Duc-Huy Chu; Tien Ngoc Nguyen; Long Van Nguyen; Tien Ngoc Tien; Tung Thanh Le; Keita Matsuno; Masatoshi Okamatsu; Yoshihiro Sakoda
    Transboundary and emerging diseases, 2021年11月04日, [最終著者, 責任著者], [国際誌]
    英語, 研究論文(学術雑誌), In South Vietnam, live bird markets (LBMs) are key in the value chain of poultry products and spread of avian influenza virus (AIV) although they may not be the sole determinant of AIV prevalence. For this reason, a risk analysis of AIV prevalence was conducted accounting for all value chain factors. A cross-sectional study of poultry flock managers and poultry on backyard farms, commercial (high biosecurity) farms, LBMs and poultry delivery stations (PDSs) in four districts of Vinh Long province was conducted between December 2016 and August 2017. A total of 3597 swab samples were collected from birds from 101 backyard farms, 50 commercial farms, 58 sellers in LBMs and 19 traders in PDSs. Swab samples were submitted for AIV isolation. At the same time a questionnaire was administered to flock managers asking them to provide details of their knowledge, attitude and practices related to avian influenza. Multiple correspondence analysis and a mixed-effects multivariable logistic regression model were developed to identify enterprise and flock manager characteristics that increased the risk of AIV positivity. A total of 274 birds were positive for AIV isolation, returning an estimated true prevalence of 7.6% [95% confidence interval (CI): 6.8%-8.5%]. The odds of a bird being AIV positive if it was from an LBM or PDS were 45 (95% CI: 3.4-590) and 25 (95% CI: 1.4-460), respectively, times higher to the odds of a bird from a commercial poultry farm being AIV positive. The odds of birds being AIV positive for respondents with a mixed (uncertain or inconsistent) level and a low level of knowledge about AI were 5.0 (95% CI: 0.20-130) and 3.5 (95% CI: 0.2-62), respectively, times higher to the odd of birds being positive for respondents with a good knowledge of AI. LBMs and PDSs should receive specific emphasis in AI control programs in Vietnam. Our findings provide evidence to support the hypothesis that incomplete respondent knowledge of AI and AIV spread mechanism were associated with an increased risk of AIV positivity. Delivery of education programs specifically designed for those in each enterprise will assist in this regard. The timing and frequency of delivery of education programs are likely to be important if the turnover of those working in LBMs and PDSs is high.
  • Serological and molecular epidemiological study on swine influenza in Zambia.
    Hayato Harima; Kosuke Okuya; Masahiro Kajihara; Hirohito Ogawa; Edgar Simulundu; Eugene Bwalya; Yongjin Qiu; Akina Mori-Kajihara; Musso Munyeme; Yoshihiro Sakoda; Takehiko Saito; Bernard M Hang'ombe; Hirofumi Sawa; Aaron S Mweene; Ayato Takada
    Transboundary and emerging diseases, 69, 4, e931-e943, 2021年11月01日, [国際誌]
    英語, 研究論文(学術雑誌), Influenza A viruses (IAVs) cause highly contagious respiratory diseases in humans and animals. In 2009, a swine-origin pandemic H1N1 IAV, designated A(H1N1)pdm09 virus, spread worldwide, and has since frequently been introduced into pig populations. Since novel reassortant IAVs with pandemic potential may emerge in pigs, surveillance for IAV in pigs is therefore necessary not only for the pig industry but also for public health. However, epidemiological information on IAV infection of pigs in Africa remains sparse. In this study, we collected 246 serum and 605 nasal swab samples from pigs in Zambia during the years 2011-2018. Serological analyses revealed that 49% and 32% of the sera collected in 2011 were positive for hemagglutination-inhibition (HI) and neutralizing antibodies against A(H1N1)pdm09 virus, respectively, whereas less than 5.3% of sera collected during the following period (2012-2018) were positive in both serological tests. The positive rate and the neutralization titres to A(H1N1)pdm09 virus were higher than those to classical swine H1N1 and H1N2 IAVs. On the other hand, the positive rate for swine H3N2 IAV was very low in the pig population in Zambia in 2011-2018 (5.3% and 0% in HI and neutralization tests, respectively). From nasal swab samples, we isolated one H3N2 and eight H1N1 IAV strains with an isolation rate of 1.5%. Phylogenetic analyses of all eight gene segments revealed that the isolated IAVs were closely related to human IAV strains belonging to A(H1N1)pdm09 and seasonal H3N2 lineages. Our findings indicate that reverse zoonotic transmission from humans to pigs occurred during the study period in Zambia and highlight the need for continued surveillance to monitor the status of IAVs circulating in swine populations in Africa.
  • Establishment of a mouse- and egg-adapted strain for the evaluation of vaccine potency against H3N2 variant influenza virus in mice.
    Enkhbold Bazarragchaa; Takahiro Hiono; Norikazu Isoda; Hirotaka Hayashi; Masatoshi Okamatsu; Yoshihiro Sakoda
    The Journal of veterinary medical science, 83, 11, 1694, 1701, 2021年10月31日, [最終著者, 責任著者], [国内誌]
    英語, 研究論文(学術雑誌), Sporadic spreads of swine-origin influenza H3N2 variant (H3N2v) viruses were reported in humans, resulting in 437 human infections between 2011 and 2021 in the USA. Thus, an effective vaccine is needed to better control a potential pandemic for these antigenically distinct viruses from seasonal influenza. In this study, a candidate vaccine strain with efficient growth capacity in chicken embryos was established through serial blind passaging of A/Indiana/08/2011 (H3N2)v in mice and chicken embryos. Seven amino acid substitutions (M21I in PA; A138T, N165K, and V226A in HA; S312L in NP; T167I in M1; G62A in NS1 proteins) were found in the passaged viruses without a major change in the antigenicity. This mouse- and egg-adapted virus was used as a vaccine and challenge strain in mice to evaluate the efficacy of the H3N2v vaccine in different doses. Antibodies with high neutralizing titers were induced in mice immunized with 100 µg of inactivated whole-virus particles, and those mice were significantly protected from the challenge of homologous strain. The findings indicated that the established strain in the study was useful for vaccine study in mouse models.
  • Sulfated glycans containing NeuAcα2-3Gal facilitate the propagation of human H1N1 influenza A viruses in eggs.
    Tomomi Ichimiya; Masatoshi Okamatsu; Takaaki Kinoshita; Daiki Kobayashi; Osamu Ichii; Naoki Yamamoto; Yoshihiro Sakoda; Hiroshi Kida; Hiroto Kawashima; Kazuo Yamamoto; Sayaka Takase-Yoden; Shoko Nishihara
    Virology, 562, 29, 39, 2021年10月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), When human influenza viruses are isolated and passaged in chicken embryos, variants with amino acid substitutions around the receptor binding site of hemagglutinin (HA) are selected; however, the mechanisms that underlie this phenomenon have yet to be elucidated. Here, we analyzed the receptor structures that contributed to propagation of egg-passaged human H1N1 viruses. The analysis included seasonal and 2009 pandemic strains, both of which have amino acid substitutions of HA found in strains isolated or passaged in eggs. These viruses exhibited high binding to sulfated glycans containing NeuAcα2-3Gal. In MDCK cells overexpressing the sulfotransferase that synthesize Galβ1-4(SO3--6)GlcNAc, production of human H1N1 viruses was increased up to 90-fold. Furthermore, these sulfated glycans were expressed on the allantoic and amniotic membranes of chicken embryos. These results suggest that 6-sulfo sialyl Lewis X and/or NeuAcα2-3Galβ1-4(SO3--6)GlcNAc are involved in efficient propagation of human H1N1 viruses in chicken embryos.
  • 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, 2021年09月20日, [国際誌]
    英語, 研究論文(学術雑誌), 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.
  • 北海道の野鳥から検出されたロタウイルスA JC-105株の遺伝学的解析
    藤井 祐至; 正谷 達謄; 西山 祥子; 藤原 拓朗; 迫田 義博; 高田 礼人; 小澤 真; 杉山 誠; 伊藤 直人
    日本獣医学会学術集会講演要旨集, 164回, [FO, 1], (公社)日本獣医学会, 2021年09月
    日本語
  • Characteristics of Classical Swine Fever Virus Variants Derived from Live Attenuated GPE- Vaccine Seed.
    Taksoo Kim; Loc Tan Huynh; Shizuka Hirose; Manabu Igarashi; Takahiro Hiono; Norikazu Isoda; Yoshihiro Sakoda
    Viruses, 13, 8, 2021年08月23日, [査読有り], [最終著者, 責任著者], [国際誌]
    英語, 研究論文(学術雑誌), The GPE- strain is a live attenuated vaccine for classical swine fever (CSF) developed in Japan. In the context of increasing attention for the differentiating infected from vaccinated animals (DIVA) concept, the achievement of CSF eradication with the GPE- proposes it as a preferable backbone for a recombinant CSF marker vaccine. While its infectious cDNA clone, vGPE-, is well characterized, 10 amino acid substitutions were recognized in the genome, compared to the original GPE- vaccine seed. To clarify the GPE- seed availability, this study aimed to generate and characterize a clone possessing the identical amino acid sequence to the GPE- seed. The attempt resulted in the loss of the infectious GPE- seed clone production due to the impaired replication by an amino acid substitution in the viral polymerase NS5B. Accordingly, replication-competent GPE- seed variant clones were produced. Although they were mostly restricted to propagate in the tonsils of pigs, similarly to vGPE-, their type I interferon-inducing capacity was significantly lower than that of vGPE-. Taken together, vGPE- mainly retains ideal properties for the CSF vaccine, compared with the seed variants, and is probably useful in the development of a CSF marker vaccine.
  • Transmission Dynamics of Bovine Viral Diarrhea Virus in Hokkaido, Japan by Phylogenetic and Epidemiological Network Approaches.
    Shizuka Hirose; Kosuke Notsu; Satoshi Ito; Yoshihiro Sakoda; Norikazu Isoda
    Pathogens (Basel, Switzerland), 10, 8, 2021年07月21日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Bovine viral diarrhea (BVD) caused by BVD virus (BVDV) leads to economic loss worldwide. Cattle that are persistently infected (PI) with BVDV are known to play an important role in viral transmission in association with the animal movement, as they shed the virus during their lifetime. In this research, the "hot spot" for BVD transmission was estimated by combining phylogenetic and epidemiological analyses for PI cattle and cattle that lived together on BVDV affected farms in Tokachi district, Hokkaido prefecture, Japan. Viral isolates were genetically categorized into BVDV-1a, 1b, and 2a, based on the nucleotide sequence of the entire E2 region. In BVDV genotype 1, subgenotype b (BVDV-1b), cluster I was identified as the majority in Tokachi district. Network analysis indicated that 12 of the 15 affected farms had cattle movements from other facilities (PI-network) and farms affected with BVDV-1b cluster I consisted of a large network. It was implied that the number of cattle movements themselves would be a risk of BVD transmission, using the PageRank algorithm. Therefore, these results demonstrate that cattle movements would contribute to disease spread and the combination of virological and epidemiological analysis methods would be beneficial in determining possible virus transmission routes.
  • The clinically used serine protease inhibitor nafamostat reduces influenza virus replication and cytokine production in human airway epithelial cells and viral replication in mice.
    Mutsuo Yamaya; Yoshitaka Shimotai; Ayako Ohkawara; Enkhbold Bazarragchaa; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Hidekazu Nishimura
    Journal of medical virology, 93, 6, 3484, 3495, 2021年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), The effects of the clinically used protease inhibitor nafamostat on influenza virus replication have not been well studied. Primary human tracheal (HTE) and nasal (HNE) epithelial cells were pretreated with nafamostat and infected with the 2009 pandemic [A/Sendai-H/108/2009/(H1N1) pdm09] or seasonal [A/New York/55/2004(H3N2)] influenza virus. Pretreatment with nafamostat reduced the titers of the pandemic and seasonal influenza viruses and the secretion of inflammatory cytokines, including interleukin-6 and tumor necrosis factor-α, in the supernatants of the cells infected with the pandemic influenza virus. HTE and HNE cells exhibited mRNA and/or protein expression of transmembrane protease serine 2 (TMPRSS2), TMPRSS4, and TMPRSS11D. Pretreatment with nafamostat reduced cleavage of the precursor protein HA0 of the pandemic influenza virus into subunit HA1 in HTE cells and reduced the number of acidic endosomes in HTE and HNE cells where influenza virus RNA enters the cytoplasm. Additionally, nafamostat (30 mg/kg/day, intraperitoneal administration) reduced the levels of the pandemic influenza virus [A/Hyogo/YS/2011 (H1N1) pdm09] in mouse lung washes. These findings suggest that nafamostat may inhibit influenza virus replication in human airway epithelial cells and mouse lungs and reduce infection-induced airway inflammation by modulating cytokine production.
  • Macrocyclic peptides exhibit antiviral effects against influenza virus HA and prevent pneumonia in animal models.
    Makoto Saito; Yasushi Itoh; Fumihiko Yasui; Tsubasa Munakata; Daisuke Yamane; Makoto Ozawa; Risa Ito; Takayuki Katoh; Hirohito Ishigaki; Misako Nakayama; Shintaro Shichinohe; Kenzaburo Yamaji; Naoki Yamamoto; Ai Ikejiri; Tomoko Honda; Takahiro Sanada; Yoshihiro Sakoda; Hiroshi Kida; Thi Quynh Mai Le; Yoshihiro Kawaoka; Kazumasa Ogasawara; Kyoko Tsukiyama-Kohara; Hiroaki Suga; Michinori Kohara
    Nature communications, 12, 1, 2654, 2654, 2021年05月11日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Most anti-influenza drugs currently used, such as oseltamivir and zanamivir, inhibit the enzymatic activity of neuraminidase. However, neuraminidase inhibitor-resistant viruses have already been identified from various influenza virus isolates. Here, we report the development of a class of macrocyclic peptides that bind the influenza viral envelope protein hemagglutinin, named iHA. Of 28 iHAs examined, iHA-24 and iHA-100 have inhibitory effects on the in vitro replication of a wide range of Group 1 influenza viruses. In particular, iHA-100 bifunctionally inhibits hemagglutinin-mediated adsorption and membrane fusion through binding to the stalk domain of hemagglutinin. Moreover, iHA-100 shows powerful efficacy in inhibiting the growth of highly pathogenic influenza viruses and preventing severe pneumonia at later stages of infection in mouse and non-human primate cynomolgus macaque models. This study shows the potential for developing cyclic peptides that can be produced more efficiently than antibodies and have multiple functions as next-generation, mid-sized biomolecules.
  • Updating the influenza virus library at Hokkaido University -It's potential for the use of pandemic vaccine strain candidates and diagnosis.
    Naoki Nomura; Keita Matsuno; Masashi Shingai; Marumi Ohno; Toshiki Sekiya; Ryosuke Omori; Yoshihiro Sakoda; Robert G Webster; Hiroshi Kida
    Virology, 557, 55, 61, 2021年05月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Genetic reassortment of influenza A viruses through cross-species transmission contributes to the generation of pandemic influenza viruses. To provide information on the ecology of influenza viruses, we have been conducting a global surveillance of zoonotic influenza and establishing an influenza virus library. Of 4580 influenza virus strains in the library, 3891 have been isolated from over 70 different bird species. The remaining 689 strains were isolated from humans, pigs, horses, seal, whale, and the environment. Phylogenetic analyses of the HA genes of the library isolates demonstrate that the library strains are distributed to all major known clusters of the H1, H2 and H3 subtypes of HA genes that are prevalent in humans. Since past pandemic influenza viruses are most likely genetic reassortants of zoonotic and seasonal influenza viruses, a vast collection of influenza A virus strains from various hosts should be useful for vaccine preparation and diagnosis for future pandemics.
  • Efficacy of Oral Vaccine against Classical Swine Fever in Wild Boar and Estimation of the Disease Dynamics in the Quantitative Approach.
    Enkhbold Bazarragchaa; Norikazu Isoda; Taksoo Kim; Madoka Tetsuo; Satoshi Ito; Keita Matsuno; Yoshihiro Sakoda
    Viruses, 13, 2, 2021年02月20日, [査読有り], [最終著者, 責任著者], [国際誌]
    英語, 研究論文(学術雑誌), Classical swine fever virus (CSFV) in the wild boar population has been spreading in Japan, alongside outbreaks on pigs, since classical swine fever (CSF) reemerged in September 2018. The vaccination using oral bait vaccine was initially implemented in Gifu prefecture in March 2019. In the present study, antibodies against CSFV in wild boar were assessed in 1443 captured and dead wild boars in Gifu prefecture. After the implementation of oral vaccination, the increase of the proportion of seropositive animals and their titer in wild boars were confirmed. Quantitative analysis of antigen and antibodies against CSFV in wild boar implies potential disease diversity in the wild boar population. Animals with status in high virus replication (Ct < 30) and non- or low-immune response were confirmed and were sustained at a certain level after initial oral vaccination. Through continuous vaccination periods, the increase of seroprevalence among wild boar and the decrease of CSFV-positive animals were observed. The epidemiological analysis based on the quantitative virological outcomes could provide more information on the efficacy of oral vaccination and dynamics of CSF in the wild boar population, which will help to improve the implementation of control measures for CSF in countries such as Japan and neighboring countries.
  • Efficacy of a Cap-Dependent Endonuclease Inhibitor and Neuraminidase Inhibitors against H7N9 Highly Pathogenic Avian Influenza Virus Causing Severe Viral Pneumonia in Cynomolgus Macaques.
    Saori Suzuki; Cong Thanh Nguyen; Ayako Ogata-Nakahara; Akihiro Shibata; Hiroyuki Osaka; Hirohito Ishigaki; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Kazumasa Ogasawara; Yasushi Itoh
    Antimicrobial agents and chemotherapy, 65, 3, 2021年02月17日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), H7N9 highly pathogenic avian influenza virus (HPAIV) infection in a human was first reported in 2017. A/duck/Japan/AQ-HE29-22/2017 (H7N9) (Dk/HE29-22), found in imported duck meat at an airport in Japan, possesses a hemagglutinin with a multibasic cleavage site, indicating high pathogenicity in chickens, as in the case of other H7 HPAIVs. In the present study, we examined the pathogenicity of Dk/HE29-22 and the effectiveness of a cap-dependent endonuclease inhibitor (baloxavir) and neuraminidase inhibitors (oseltamivir and zanamivir) against infection with this strain in a macaque model (n = 3 for each group). All of the macaques infected with Dk/HE29-22 showed severe signs of disease and pneumonia even after the virus had disappeared from lung samples. Virus titers in macaques treated with baloxavir were significantly lower than those in the other treated groups. After infection, levels of interferon alpha and beta (IFN-α and IFN-β) in the blood of macaques in the baloxavir group were the highest among the groups, whereas levels of tumor necrosis factor alpha (TNF-α) and interleukin 13 (IL-13) were slightly increased in the untreated group. In addition, immune checkpoint proteins, including programmed death 1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), were expressed at high levels in the untreated group, especially in one macaque that showed severe signs of disease, indicating that negative feedback responses against vigorous inflammation may contribute to disease progression. In the group treated with baloxavir, the percentages of PD-1-, CTLA-4-, and TIGIT-positive T lymphocytes were lower than those in the untreated group, indicating that reduction in virus titers may prevent expression of immune checkpoint molecules from downregulation of T cell responses.
  • Author Correction: Data mining and model-predicting a global disease reservoir for low-pathogenic Avian Influenza (AI) in the wider Pacific Rim using big data sets.
    Marina Gulyaeva; Falk Huettmann; Alexander Shestopalov; Masatoshi Okamatsu; Keita Matsuno; Duc-Huy Chu; Yoshihiro Sakoda; Alexandra Glushchenko; Elaina Milton; Eric Bortz
    Scientific reports, 11, 1, 3758, 3758, 2021年02月08日, [査読有り], [国際誌]
    英語
  • A New Variant Among Newcastle Disease Viruses Isolated in the Democratic Republic of the Congo in 2018 and 2019.
    Augustin T Twabela; Lam Thanh Nguyen; Justin Masumu; Patrick Mpoyo; Serge Mpiana; Julienne Sumbu; Masatoshi Okamatsu; Keita Matsuno; Norikazu Isoda; Bianca Zecchin; Isabella Monne; Yoshihiro Sakoda
    Viruses, 13, 2, 2021年01月20日, [査読有り], [最終著者, 責任著者], [国際誌]
    英語, 研究論文(学術雑誌), Newcastle disease (ND) is a highly transmissible and devastating disease that affects poultry and wild birds worldwide. Comprehensive knowledge regarding the characteristics and epidemiological factors of the ND virus (NDV) is critical for the control and prevention of ND. Effective vaccinations can prevent and control the spread of the NDV in poultry populations. For decades, the Democratic Republic of the Congo (DRC) has reported the impacts of ND on commercial and traditional poultry farming systems. The reports were preliminary clinical observations, and few cases were confirmed in the laboratory. However, data on the phylogenetic, genetic, and virological characteristics of NDVs circulating in the DRC are not available. In this study, the whole-genome sequences of three NDV isolates obtained using the next-generation sequencing method revealed two isolates that were a new variant of NDV, and one isolate that was clustered in the subgenotype VII.2. All DRC isolates were velogenic and were antigenically closely related to the vaccine strains. Our findings reveal that despite the circulation of the new variant, ND can be controlled in the DRC using the current vaccine. However, epidemiological studies should be conducted to elucidate the endemicity of the disease so that better control strategies can be implemented.
  • Potency of an Inactivated Influenza Vaccine against a Challenge with A/Swine/Missouri/A01727926/2015 (H4N6) in Mice for Pandemic Preparedness.
    Hirotaka Hayashi; Norikazu Isoda; Enkhbold Bazarragchaa; Naoki Nomura; Keita Matsuno; Masatoshi Okamatsu; Hiroshi Kida; Yoshihiro Sakoda
    Vaccines, 8, 4, 2020年12月16日, [査読有り], [最終著者, 責任著者], [国際誌]
    英語, 研究論文(学術雑誌), H4 influenza viruses have been isolated from birds across the world. In recent years, an H4 influenza virus infection has been confirmed in pigs. Pigs play an important role in the transmission of influenza viruses to human hosts. Therefore, it is important to develop a new vaccine in the case of an H4 influenza virus infection in humans, considering that this virus has a different antigenicity from seasonal human influenza viruses. In this study, after selecting vaccine candidate strains based on their antigenic relation to one of the pig isolates, A/swine/Missouri/A01727926/2015 (H4N6) (MO/15), an inactivated whole-particle vaccine was prepared from A/swan/Hokkaido/481102/2017 (H4N6). This vaccine showed high immunogenicity in mice, and the antibody induced by the vaccine showed high cross-reactivity to the MO/15 virus. This vaccine induced sufficient neutralizing antibodies and mitigated the effects of an MO/15 infection in a mouse model. This study is the first to suggest that an inactivated whole-particle vaccine prepared from an influenza virus isolated from wild birds is an effective countermeasure in case of a future influenza pandemic caused by the H4 influenza virus.
  • Re-Invasion of H5N8 High Pathogenicity Avian Influenza Virus Clade 2.3.4.4b in Hokkaido, Japan, 2020.
    Norikazu Isoda; Augustin T Twabela; Enkhbold Bazarragchaa; Kohei Ogasawara; Hirotaka Hayashi; Zu-Jyun Wang; Daiki Kobayashi; Yukiko Watanabe; Keisuke Saito; Hiroshi Kida; Yoshihiro Sakoda
    Viruses, 12, 12, 2020年12月14日, [査読有り], [最終著者, 責任著者], [国際誌]
    英語, 研究論文(学術雑誌), Global dispersion of high pathogenicity avian influenza (HPAI), especially that caused by H5 clade 2.3.4.4, has threatened poultry industries and, potentially, human health. An HPAI virus, A/northern pintail/Hokkaido/M13/2020 (H5N8) (NP/Hok/20) belonging to clade 2.3.4.4b, was isolated from a fecal sample collected at a lake in Hokkaido, Japan where migratory birds rested, October 2020. In the phylogenetic trees of all eight gene segments, NP/Hok/20 fell into in the cluster of European isolates in 2020, but was distinct from the isolates in eastern Asia and Europe during the winter season of 2017-2018. The antigenic cartography indicates that the antigenicity of NP/Hok/20 was almost the same as that of previous isolates of H5 clade 2.3.4.4b, whereas the antigenic distances from NP/Hok/20 to the representative strains in clade 2.3.4.4e and to a strain in 2.3.4 were apparently distant. These data imply that HPAI virus clade 2.3.4.4b should have been delivered by bird migration despite the intercontinental distance, although it was not defined whether NP/Hok/20 was transported from Europe via Siberia where migratory birds nest in the summer season. Given the probability of perpetuation of transmission in the northern territory, periodic updates of intensive surveys on avian influenza at the global level are essential to prepare for future outbreaks of the HPAI virus.
  • Evaluation of Baloxavir Marboxil and Peramivir for the Treatment of High Pathogenicity Avian Influenza in Chickens.
    Augustin Twabela; Masatoshi Okamatsu; Keita Matsuno; Norikazu Isoda; Yoshihiro Sakoda
    Viruses, 12, 12, 2020年12月08日, [査読有り], [最終著者, 責任著者], [国際誌]
    英語, 研究論文(学術雑誌), Control measures in the case of high pathogenicity avian influenza (HPAI) outbreaks in poultry include culling, surveillance, and biosecurity; wild birds in captivity may also be culled, although some rare bird species should be rescued for conservation. In this study, two anti-influenza drugs, baloxavir marboxil (BXM) and peramivir (PR), used in humans, were examined in treating HPAI in birds, using chickens as a model. Chickens were infected with H5N6 HPAI virus and were treated immediately or 24 h from challenge with 20 mg/kg BXM or PR twice a day for five days. As per our findings, BXM significantly reduced virus replication in organs and provided full protection to chickens compared with that induced by PR. In the 24-h-delayed treatment, neither drug completely inhibited virus replication nor ensured the survival of infected chickens. A single administration of 2.5 mg/kg of BXM was determined as the minimum dose required to fully protect chickens from HPAI virus; the concentration of baloxavir acid, the active form of BXM, in chicken blood at this dose was sufficient for a 48 h antiviral effect post-administration. Thus, these data can be a starting point for the use of BXM and PR in treating captive wild birds infected with HPAI virus.
  • Classical swine fever virus: the past, present and future.
    Llilianne Ganges; Helen R Crooke; Jose Alejandro Bohórquez; Alexander Postel; Yoshihiro Sakoda; Paul Becher; Nicolas Ruggli
    Virus research, 289, 198151, 198151, 2020年11月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Classical swine fever (CSF) is among the most relevant viral epizootic diseases of swine. Due to its severe economic impact, CSF is notifiable to the world organisation for animal health. Strict control policies, including systematic stamping out of infected herds with and without vaccination, have permitted regional virus eradication. Nevertheless, CSF virus (CSFV) persists in certain areas of the world and has re-emerged regularly. This review summarizes the basic established knowledge in the field and provides a comprehensive and updated overview of the recent advances in fundamental CSFV research, diagnostics and vaccine development. It covers the latest discoveries on the genetic diversity of pestiviruses, with implications for taxonomy, the progress in understanding disease pathogenesis, immunity against acute and persistent infections, and the recent findings in virus-host interactions and virulence determinants. We also review the progress and pitfalls in the improvement of diagnostic tools and the challenges in the development of modern and efficacious marker vaccines compatible with serological tests for disease surveillance. Finally, we highlight the gaps that require research efforts in the future.
  • Cell-penetrating peptide-mediated cell entry of H5N1 highly pathogenic avian influenza virus.
    Naoki Kajiwara; Namiko Nomura; Masako Ukaji; Naoki Yamamoto; Michinori Kohara; Fumihiko Yasui; Yoshihiro Sakoda; Hiroshi Kida; Futoshi Shibasaki
    Scientific reports, 10, 1, 18008, 18008, 2020年10月22日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), H5N1 highly pathogenic avian influenza virus (HPAIV) poses a huge threat to public health and the global economy. These viruses cause systemic infection in poultry and accidental human infection leads to severe pneumonia, associated with high mortality rates. The hemagglutinin (HA) of H5N1 HPAIV possesses multiple basic amino acids, as in the sequence RERRRKKR at the cleavage site; however, the role of this motif is not fully understood. Here, we showed that a 33-amino acid long peptide derived from HA of H5N1 HPAIV (HA314-46) has the potential to penetrate various cells and lung tissue through a sialic acid-independent endocytotic pathway. Mutant peptide analyses revealed that the cysteine residue at position 318 and multiple basic amino acids were essential for the cell-penetrating activity. Moreover, reassortant viruses possessing H5 HA could enter sialic acid-deficient cells, and virus internalisation was facilitated by cleavage with recombinant furin. Thus, our findings demonstrate that the HA314-46 motif exhibits cell-penetrating activity through a sialic acid-independent cell entry mechanism.
  • Data mining and model-predicting a global disease reservoir for low-pathogenic Avian Influenza (A) in the wider pacific rim using big data sets.
    Marina Gulyaeva; Falk Huettmann; Alexander Shestopalov; Masatoshi Okamatsu; Keita Matsuno; Duc-Huy Chu; Yoshihiro Sakoda; Alexandra Glushchenko; Elaina Milton; Eric Bortz
    Scientific reports, 10, 1, 16817, 16817, 2020年10月08日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Avian Influenza (AI) is a complex but still poorly understood disease; specifically when it comes to reservoirs, co-infections, connectedness and wider landscape perspectives. Low pathogenic (Low-path LP) AI in chickens caused by less virulent strains of AI viruses (AIVs)-when compared with highly pathogenic AIVs (HPAIVs)-are not even well-described yet or known how they contribute to wider AI and immune system issues. Co-circulation of LPAIVs with HPAIVs suggests their interactions in their ecological aspects. Here we show for the Pacific Rim an international approach how to data mine and model-predict LP AI and its ecological niche with machine learning and open access data sets and geographic information systems (GIS) on a 5 km pixel size for best-possible inference. This is based on the best-available data on the issue (~ 40,827 records of lab-analyzed field data from Japan, Russia, Vietnam, Mongolia, Alaska and Influenza Research Database (IRD) and U.S. Department of Agriculture (USDA) database sets, as well as 19 GIS data layers). We sampled 157 hosts and 110 low-path AIVs with 32 species as drivers. The prevalence across low-path AIV subtypes is dominated by Muscovy ducks, Mallards, Whistling Swans and gulls also emphasizing industrial impacts for the human-dominated wildlife contact zone. This investigation sets a good precedent for the study of reservoirs, big data mining, predictions and subsequent outbreaks of HPAI and other pandemics.
  • Genetic and antigenic characterization of H5 and H7 avian influenza viruses isolated from migratory waterfowl in Mongolia from 2017 to 2019.
    Ankhanbaatar Ulaankhuu; Enkhbold Bazarragchaa; Masatoshi Okamatsu; Takahiro Hiono; Khishgee Bodisaikhan; Tsolmon Amartuvshin; Jargalsaikhan Tserenjav; Tsogtbaatar Urangoo; Khanui Buyantogtokh; Keita Matsuno; Takanari Hattori; Tatsunari Kondoh; Masahiro Sato; Yoshihiro Takadate; Shiho Torii; Mao Isono; Kosuke Okuya; Takeshi Saito; Nodoka Kasajima; Yurie Kida; Junki Maruyama; Manabu Igarashi; Ayato Takada; Hiroshi Kida; Damdinjav Batchuluun; Yoshihiro Sakoda
    Virus genes, 56, 4, 472, 479, 2020年08月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), 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.
  • Oral Supplementation of the Vitamin D Metabolite 25(OH)D3 Against Influenza Virus Infection in Mice.
    Hirotaka Hayashi; Masatoshi Okamatsu; Honami Ogasawara; Naoko Tsugawa; Norikazu Isoda; Keita Matsuno; Yoshihiro Sakoda
    Nutrients, 12, 7, 2020年07月05日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Vitamin D is a fat-soluble vitamin that is metabolized by the liver into 25-hydroxyvitamin D [25(OH)D] and then by the kidney into 1,25-dihydroxyvitamin D [1,25(OH)2D], which activates the vitamin D receptor expressed in various cells, including immune cells, for an overall immunostimulatory effect. Here, to investigate whether oral supplementation of 25-hydroxyvitamin D3 [25(OH)D3], a major form of vitamin D metabolite 25(OH)D, has a prophylactic effect on influenza A virus infection, mice were fed a diet containing a high dose of 25(OH)D3 and were challenged with the influenza virus. In the lungs of 25(OH)D3-fed mice, the viral titers were significantly lower than in the lungs of standardly fed mice. Additionally, the proinflammatory cytokines IL-5 and IFN-γ were significantly downregulated after viral infection in 25(OH)D3-fed mice, while anti-inflammatory cytokines were not significantly upregulated. These results indicate that 25(OH)D3 suppresses the production of inflammatory cytokines and reduces virus replication and clinical manifestations of influenza virus infection in a mouse model.
  • Efficacy of Neuraminidase Inhibitors against H5N6 Highly Pathogenic Avian Influenza Virus in a Nonhuman Primate Model.
    Cong Thanh Nguyen; Saori Suzuki; Yasushi Itoh; Hirohito Ishigaki; Misako Nakayama; Kaori Hayashi; Keita Matsuno; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Kazumasa Ogasawara
    Antimicrobial agents and chemotherapy, 64, 7, 2020年06月23日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Attention has been paid to H5N6 highly pathogenic avian influenza virus (HPAIV) because of its heavy burden on the poultry industry and human mortality. Since an influenza A virus carrying N6 neuraminidase (NA) has never spread in humans, the potential for H5N6 HPAIV to cause disease in humans and the efficacy of antiviral drugs against the virus need to be urgently assessed. We used nonhuman primates to elucidate the pathogenesis of H5N6 HPAIV as well as to determine the efficacy of antiviral drugs against the virus. H5N6 HPAIV infection led to high fever in cynomolgus macaques. The lung injury caused by the virus was severe, with diffuse alveolar damage and neutrophil infiltration. In addition, an increase in interferon alpha (IFN-α) showed an inverse correlation with virus titers during the infection process. Oseltamivir was effective for reducing H5N6 HPAIV propagation, and continuous treatment with peramivir reduced virus propagation and the severity of symptoms in the early stage. This study also showed pathologically severe lung injury states in cynomolgus macaques infected with H5N6 HPAIV, even in those that received early antiviral drug treatments, indicating the need for close monitoring and further studies on virus pathogenicity and new antiviral therapies.
  • Low replicative fitness of neuraminidase inhibitor-resistant H7N9 avian influenza a virus with R292K substitution in neuraminidase in cynomolgus macaques compared with I222T substitution.
    Saori Suzuki; Shintaro Shichinohe; Yasushi Itoh; Misako Nakayama; Hirohito Ishigaki; Yuya Mori; Ayako Ogata-Nakahara; Cong Thanh Nguyen; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Kazumasa Ogasawara
    Antiviral research, 178, 104790, 104790, 2020年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Human cases of H7N9 influenza A virus infection have been increasing since 2013. The first choice of treatment for influenza is neuraminidase (NA) inhibitors (NAIs), but there is a concern that NAI-resistant viruses are selected in the presence of NAIs. In our previous study, an H7N9 virus carrying AA substitution of threonine (T) for isoleucine (I) at residue 222 in NA (NA222T, N2 numbering) and an H7N9 virus carrying AA substitution of lysine (K) for arginine (R) at residue 292 in NA (NA292K, N2 numbering) were found in different macaques that had been infected with A/Anhui/1/2013 (H7N9) and treated with NAIs. In the present study, the variant with NA292K showed not only resistance to NAIs but also lower replication activity in MDCK cells than did the virus with wild-type NA, whereas the variant with NA222T, which was less resistant to NAIs, showed replication activity similar to that of the wild-type virus. Next, we examined the pathogenicity of these H7N9 NAI-resistant viruses in macaques. The variants caused clinical signs similar to those caused by the wild-type virus with similar replication potency. However, the virus with NA292K was replaced within 7 days by that with NA292R (same as the wild-type) in nasal samples from macaques infected with the virus with NA292K, i.e. the so-called revertant (wild-type virus) became dominant in the population in the absence of an NAI. These results suggest that the clinical signs observed in macaques infected with the NA292K virus are caused by the NA292K virus and the NA292R virus and that the virus with NA292K may not replicate continuously in the upper respiratory tract of patients without treatment as effectively as the wild-type virus.
  • Detection of avian influenza virus: a comparative study of the in silico and in vitro performances of current RT-qPCR assays.
    Andrea Laconi; Andrea Fortin; Giulia Bedendo; Akihiro Shibata; Yoshihiro Sakoda; Joseph Adongo Awuni; Emilie Go-Maro; Abdelsatar Arafa; Ali Safar Maken Ali; Calogero Terregino; Isabella Monne
    Scientific reports, 10, 1, 8441, 8441, 2020年05月21日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Avian influenza viruses (AIV) are negative sense RNA viruses posing a major threat to the poultry industry worldwide, with the potential to spread to mammals, including humans; hence, an accurate and rapid AIV diagnosis is essential. To date AIV detection relies on molecular methods, mainly RT-qPCR directed against AIV M gene segment. The evolution of AIV represents a relevant issue in diagnostic RT-qPCR due to possible mispriming and/or probe-binding failures resulting in false negative results. Consequently, RT-qPCR for AIV detection should be periodically re-assessed both in silico and in vitro. To this end, a specific workflow was developed to evaluate in silico the complementarity of primers and probes of four published RT-qPCR protocols to their target regions. The four assays and one commercially available kit for AIV detection were evaluated both for their analytical sensitivity using eight different viral dilution panels and for their diagnostic performances against clinical specimens of known infectious status. Differences were observed among the tests under evaluation, both in terms of analytical sensitivity and of diagnostic performances. This finding confirms the importance of continuously monitoring the primers and probes complementarity to their binding regions.
  • Spatiotemporal and risk analysis of H5 highly pathogenic avian influenza in Vietnam, 2014-2017.
    Lam Thanh Nguyen; Mark A Stevenson; Simon M Firestone; Leslie D Sims; Duc Huy Chu; Long Van Nguyen; Tien Ngoc Nguyen; Kien Trung Le; Norikazu Isoda; Keita Matsuno; Masatoshi Okamatsu; Hiroshi Kida; Yoshihiro Sakoda
    Preventive veterinary medicine, 178, 104678, 104678, 2020年05月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), The aim of this study was to describe the spatiotemporal distribution of H5 HPAI outbreak reports for the period 2014-2017 and to identify factors associated with H5 HPAI outbreak reports. Throughout the study period, a total of 139 outbreaks of H5 HPAI in poultry were reported, due to either H5N1 (96 outbreaks) or H5N6 (43 outbreaks) subtype viruses. H5N1 HPAI outbreaks occurred in all areas of Vietnam while H5N6 HPAI outbreaks were only reported in the northern and central provinces. We counted the number of H5N1 and H5N6 outbreak report-positive districts per province over the four-year study period and calculated the provincial-level standardized morbidity ratio for H5N1 and H5N6 outbreak reports as the observed number of positive districts divided by the expected number. A mixed-effects, zero-inflated Poisson regression model was developed to identify risk factors for outbreak reports of each H5N1 and H5N6 subtype virus. Spatially correlated and uncorrelated random effects terms were included in this model to identify areas of the country where outbreak reports occurred after known risk factors had been accounted-for. The presence of an outbreak report in a province in the previous 6-12 months increased the provincial level H5N1 outbreak report risk by a factor of 2.42 (95% Bayesian credible interval [CrI] 1.27-4.60) while 1000 bird increases in the density of chickens decreased provincial level H5N6 outbreak report risk by a factor of 0.65 (95% CrI 0.38 to 0.97). We document distinctly different patterns in the spatial and temporal distribution of H5N1 and H5N6 outbreak reports. Most of the variation in H5N1 report risk was accounted-for by the fixed effects included in the zero-inflated Poisson model. In contrast, the amount of unaccounted-for risk in the H5N6 model was substantially greater than the H5N1 model. For H5N6 we recommend that targeted investigations should be carried out in provinces with relatively large spatially correlated random effect terms to identify likely determinants of disease. Similarly, investigations should be carried out in provinces with relatively low spatially correlated random effect terms to identify protective factors for disease and/or reasons for failure to report.
  • E190V substitution of H6 hemagglutinin is one of key factors for binding to sulfated sialylated glycan receptor and infection to chickens.
    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, 64, 4, 304, 312, 2020年04月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), 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.
  • Development of a High-Throughput Serum Neutralization Test Using Recombinant Pestiviruses Possessing a Small Reporter Tag.
    Madoka Tetsuo; Keita Matsuno; Tomokazu Tamura; Takasuke Fukuhara; Taksoo Kim; Masatoshi Okamatsu; Norbert Tautz; Yoshiharu Matsuura; Yoshihiro Sakoda
    Pathogens (Basel, Switzerland), 9, 3, 2020年03月04日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), A serum neutralization test (SNT) is an essential method for the serological diagnosis of pestivirus infections, including classical swine fever, because of the cross reactivity of antibodies against pestiviruses and the non-quantitative properties of antibodies in an enzyme-linked immunosorbent assay. In conventional SNTs, an immunoperoxidase assay or observation of cytopathic effect after incubation for 3 to 7 days is needed to determine the SNT titer, which requires labor-intensive or time-consuming procedures. Therefore, a new SNT, based on the luciferase system and using classical swine fever virus, bovine viral diarrhea virus, and border disease virus possessing the 11-amino-acid subunit derived from NanoLuc luciferase was developed and evaluated; this approach enabled the rapid and easy determination of the SNT titer using a luminometer. In the new method, SNT titers can be determined tentatively at 2 days post-infection (dpi) and are comparable to those obtained by conventional SNTs at 3 or 4 dpi. In conclusion, the luciferase-based SNT can replace conventional SNTs as a high-throughput antibody test for pestivirus infections.
  • Genetic and antigenic characterization of the first H7N7 low pathogenic avian influenza viruses isolated in Vietnam.
    Kien Trung Le; Masatoshi Okamatsu; Lam Thanh Nguyen; Keita Matsuno; Duc-Huy Chu; Tien Ngoc Tien; Tung Thanh Le; Hiroshi Kida; Yoshihiro Sakoda
    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 78, 104117, 104117, 2020年03月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), During the annual surveillance of avian influenza viruses (AIVs) in Vietnam in 2018, three H7N7 AIV isolates were identified in domestic ducks in a single flock in Vinh Long province. The present study is the first documented report of H7N7 virus isolates in Vietnam and aimed to characterize these viruses, both genetically and antigenically. Deduced amino acid sequences for the hemagglutinins (HAs) indicated a low pathogenicity of these viruses in chickens. Phylogenetic analysis revealed that the H7 HA genes of these isolates were closely related to each other and belonged to the European-Asian sublineage, together with those of H7N3 viruses isolated from ducks in Cambodia during 2017. They were not genetically related to those of Chinese H7N9 or H7N1 viruses that were previously detected in Vietnam during 2012. Interestingly, the M genes of the two H7N7 virus isolates were phylogenetically classified into distinct groups, suggesting an ongoing reassortment event in domestic ducks because they were isolated from the same flock. These H7N7 viruses exhibited somewhat different antigenic characteristics compared with other representative H7 low pathogenic AIVs. Surprisingly, the antigenicity of Vietnamese H7N7 viruses is similar to Chinese H7N9 highly pathogenic AIV. The findings of this study suggest that H7N7 viruses may be undergoing reassortment and antigenic diversification in poultry flocks in Vietnam. The silent spread of Vietnamese H7N7 viruses in chickens may lead to acquire high pathogenicity in chickens although the zoonotic potential of the viruses seems to be low since these viruses retain typical avian-specific motifs in the receptor-binding site in the HA and there is no mutation related to mammalian adaptation in PB2 gene. Thus, these results highlight the need for continuous and intensive surveillance of avian influenza in Vietnam, targeting not only highly pathogenic AIVs but also low pathogenic viruses.
  • Dynamics of Classical Swine Fever Spread in Wild Boar in 2018-2019, Japan.
    Norikazu Isoda; Kairi Baba; Satoshi Ito; Mitsugi Ito; Yoshihiro Sakoda; Kohei Makita
    Pathogens (Basel, Switzerland), 9, 2, 2020年02月13日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), The prolongation of the classic swine fever (CSF) outbreak in Japan in 2018 was highly associated with the persistence and widespread of the CSF virus (CSFV) in the wild boar population. To investigate the dynamics of the CSF outbreak in wild boar, spatiotemporal analyses were performed. The positive rate of CSFV in wild boar fluctuated dramatically from March to June 2019, but finally stabilized at approximately 10%. The Euclidean distance from the initial CSF notified farm to the farthest infected wild boar of the day constantly increased over time since the initial outbreak except in the cases reported from Gunma and Saitama prefectures. The two-month-period prevalence, estimated using integrated nested Laplace approximation, reached >80% in half of the infected areas in March-April 2019. The area affected continued to expand despite the period prevalence decreasing up to October 2019. A large difference in the shapes of standard deviational ellipses and in the location of their centroids when including or excluding cases in Gunma and Saitama prefectures indicates that infections there were unlikely to have been caused simply by wild boar activities, and anthropogenic factors were likely involved. The emergence of concurrent space-time clusters in these areas after July 2019 indicated that CSF outbreaks were scattered by this point in time. The results of this epidemiological analysis help explain the dynamics of the spread of CSF and will aid in the implementation of control measures, including bait vaccination.
  • A cloned classical swine fever virus derived from the vaccine strain GPE- causes cytopathic effect in CPK-NS cells via type-I interferon-dependent necroptosis.
    Yukari Itakura; Keita Matsuno; Asako Ito; Markus Gerber; Matthias Liniger; Yuri Fujimoto; Tomokazu Tamura; Ken-Ichiro Kameyama; Masatoshi Okamatsu; Nicolas Ruggli; Hiroshi Kida; Yoshihiro Sakoda
    Virus research, 276, 197809, 197809, 2020年01月15日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Classical swine fever viruses (CSFVs) do typically not show cytopathic effect (CPE) in cell culture, while some strains such as vaccine strain the GPE- induce CPE in the swine kidney-derived CPK-NS cell line cultured in serum-free medium. These latter strains commonly lack Npro-mediated inhibition of type-I interferon (IFN) induction. In order to explore the molecular mechanisms of GPE--induced CPE, we analyzed the cellular pathways involved. In CPK-NS cells infected with the attenuated-vaccine-derived vGPE- strain, both, apoptosis and necroptosis were induced. Necroptosis was type-I IFN-dependent and critical for visible CPE. In contrast, the parental virulent vALD-A76 strain did not induce any of these pathways nor CPE. We used reverse genetics to investigate which viral factors regulate these cell-death pathways. Interestingly, a mutant vGPE- in which the Npro function was restored to inhibit type-I IFN induction did not induce necroptosis nor CPE but still induced apoptosis, while an Npro-mutant vALD-A76 incapable of inhibiting type-I IFN production induced necroptosis and CPE. Although Erns of CSFV is reportedly involved in controlling apoptosis, apoptosis induction by vGPE- or apoptosis inhibition by vALD-A76 were independent of the unique amino acid difference found in Erns of these two strains. Altogether, these results demonstrate that type-I IFN-dependent necroptosis related to non-functional Npro is the main mechanism for CPE induction by vGPE-, and that viral factor(s) other than Erns may induce or inhibit apoptosis in vGPE- or vALD-A76 infected CPK-NS cells, respectively.
  • 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年
    研究論文(学術雑誌)
  • Molecular, antigenic, and pathogenic characterization of H5N8 highly pathogenic avian influenza viruses isolated in the Democratic Republic of Congo in 2017.
    Augustin T Twabela; Masatoshi Okamatsu; Georges Mbuyi Tshilenge; Serge Mpiana; Justin Masumu; Lam Thanh Nguyen; Keita Matsuno; Isabella Monne; Bianca Zecchin; Yoshihiro Sakoda
    Archives of virology, 165, 1, 87, 96, 2020年01月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), In May 2017, high mortality of chickens and Muscovy ducks due to the H5N8 highly pathogenic avian influenza virus (HPAIV) was reported in the Democratic Republic of Congo (DR Congo). In this study, we assessed the molecular, antigenic, and pathogenic features in poultry of the H5N8 HPAIV from the 2017 Congolese outbreaks. Phylogenetic analysis of the eight viral gene segments revealed that all 12 DR Congo isolates clustered in clade 2.3.4.4B together with other H5N8 HPAIVs isolated in Africa and Eurasia, suggesting a possible common origin of these viruses. Antigenically, a slight difference was observed between the Congolese isolates and a representative virus from group C in the same clade. After intranasal inoculation with a representative DR Congo virus, high pathogenicity was observed in chickens and Muscovy ducks but not in Pekin ducks. Viral replication was higher in chickens than in Muscovy duck and Pekin duck organs; however, neurotropism was pronounced in Muscovy ducks. Our data confirmed the high pathogenicity of the DR Congo virus in chickens and Muscovy ducks, as observed in the field. National awareness and strengthening surveillance in the region are needed to better control HPAIVs.
  • END-phenomenon negative bovine viral diarrhea virus that induces the host's innate immune response supports propagation of BVDVs with different immunological properties.
    Mai Shiokawa; Tsutomu Omatsu; Yukie Katayama; Kaoru Nishine; Yuri Fujimoto; Shiori Uchiyama; Ken-Ichiro Kameyama; Makoto Nagai; Tetsuya Mizutani; Yoshihiro Sakoda; Akio Fukusho; Hiroshi Aoki
    Virology, 538, 97, 110, 2019年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Our previous study reported that persistently infected (PI) cattle of bovine viral diarrhea virus (BVDV) have co-infected with BVDV/END- and /END+ that promote and inhibit host's type-I interferon (IFN) production, respectively. However, the relationship between co-infection of immunologically distinct BVDVs and persistent infection as well as the biological significance of END- viruses remains unknown. Experiments using cultured cells revealed that END+ virus, which is unable to propagate in situations where the host's immune response is induced by IFN-α addition, is able to propagate under those conditions when co-infecting with END- virus. These results indicate that BVDV/END- can coexist with BVDV/END+ and that co-infection with END- viruses supports the propagation of END+ viruses. Our in vitro experiments strongly suggest that co-infection with END- virus is involved in the maintenance of persistent infection of BVDV.
  • In Vivo Dynamics of Reporter Flaviviridae Viruses.
    Tomokazu Tamura; Manabu Igarashi; Bazarragchaa Enkhbold; Tatsuya Suzuki; Masatoshi Okamatsu; Chikako Ono; Hiroyuki Mori; Takuma Izumi; Asuka Sato; Yuzy Fauzyah; Toru Okamoto; Yoshihiro Sakoda; Takasuke Fukuhara; Yoshiharu Matsuura
    Journal of virology, 93, 22, 2019年11月15日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Recombinant viruses possessing reporter proteins have been generated for virus research. In the case of the family Flaviviridae, we recently generated recombinant viruses, including the hepatitis C virus of the genus Hepacivirus, Japanese encephalitis virus (JEV) of the genus Flavivirus, and bovine viral diarrhea virus of the genus Pestivirus; all three viruses possess an 11-amino-acid subunit derived from NanoLuc luciferase (HiBiT). Here, we further developed the recombinant viruses and investigated their utility in vivo Recombinant viruses harboring HiBiT in the E, NS1, or NS3 protein constructed based on the predicted secondary structure, solvent-accessible surface area, and root mean square fluctuation of the proteins exhibited comparable replication to that of the wild-type virus in vitro The recombinant JEV carrying HiBiT in the NS1 protein exhibited propagation in mice comparable to that of the parental virus, and propagation of the recombinant was monitored by the luciferase activity. In addition, the recombinants of classical swine fever virus (CSFV) possessing HiBiT in the Erns or E2 protein also showed propagation comparable to that of the wild-type virus. The recombinant CSFV carrying HiBiT in Erns exhibited similar replication to the parental CSFV in pigs, and detection of viral propagation of this recombinant by luciferase activity was higher than that by quantitative PCR (qPCR). Taken together, these results demonstrated that the reporter Flaviviridae viruses generated herein are powerful tools for elucidating the viral life cycle and pathogeneses and provide a robust platform for the development of novel antivirals.IMPORTANCEIn vivo applications of reporter viruses are necessary to understand viral pathogenesis and provide a robust platform for antiviral development. In developing such applications, determination of an ideal locus to accommodate foreign genes is important, because insertion of foreign genes into irrelevant loci can disrupt the protein functions required for viral replication. Here, we investigated the criteria to determine ideal insertion sites of foreign genes from the protein structure of viral proteins. The recombinant viruses generated by our criteria exhibited propagation comparable to that of parental viruses in vivo Our proteomic approach based on the flexibility profile of viral proteins may provide a useful tool for constructing reporter viruses, including Flaviviridae viruses.
  • Broad and systemic immune-modulating capacity of plant-derived dsRNA.
    Hajake T; Matsuno K; M Kasumba D; Oda H; Kobayashi M; Miyata N; Shinji M; Kogure A; Kasajima N; Okamatsu M; Sakoda Y; Kato H; Fujita T
    International immunology, 31, 12, 811, 821, 2019年11月08日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Double-stranded RNA (dsRNA) is well characterized as an inducer of anti-viral interferon responses. We previously reported that dsRNA extracted from a specific edible plant possesses an immune-modulating capacity to confer, in mice, resistance against respiratory viruses, including the H1N1 strain of the influenza A virus (IAV). We report here that the systemic immune-activating capacity of the plant-derived dsRNA protected mice from infection by a highly virulent H5N1 strain of the IAV. In addition, subcutaneous inoculation of the dsRNA together with the inactivated virion of the H5N1 strain of the IAV suppressed the lethality of the viral infection as compared with individual inoculation of either dsRNA or HA protein, suggesting its potential usage as a vaccination adjuvant. Moreover, intra-peritoneal inoculation of the dsRNA limited the growth of B16-F10 melanoma cells through the activation of NK cells in murine models. Taken together, this study demonstrated the systemic immune-modulating capacity of a plant-derived dsRNA and its potential for nucleic acid-based clinical applications.
  • Role of Wild Boar in the Spread of Classical Swine Fever in Japan.
    Satoshi Ito; Cristina Jurado; Jaime Bosch; Mitsugi Ito; José Manuel Sánchez-Vizcaíno; Norikazu Isoda; Yoshihiro Sakoda
    Pathogens (Basel, Switzerland), 8, 4, 2019年10月24日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Since September 2018, nearly 900 notifications of classical swine fever (CSF) have been reported in Gifu Prefecture (Japan) affecting domestic pig and wild boar by the end of August 2019. To determine the epidemiological characteristics of its spread, a spatio-temporal analysis was performed using actual field data on the current epidemic. The spatial study, based on standard deviational ellipses of official CSF notifications, showed that the disease likely spread to the northeast part of the prefecture. A maximum significant spatial association estimated between CSF notifications was 23 km by the multi-distance spatial cluster analysis. A space-time permutation analysis identified two significant clusters with an approximate radius of 12 and 20 km and 124 and 98 days of duration, respectively. When the area of the identified clusters was overlaid on a map of habitat quality, approximately 82% and 75% of CSF notifications, respectively, were found in areas with potential contact between pigs and wild boar. The obtained results provide information on the current CSF epidemic, which is mainly driven by wild boar cases with sporadic outbreaks on domestic pig farms. These findings will help implement control measures in Gifu Prefecture.
  • Slaughterhouse survey for detection of bovine viral diarrhea infection among beef cattle in Kyushu, Japan.
    Mohammad Aref Agah; Kosuke Notsu; Heba M El-Khaiat; Genki Arikawa; Meiko Kubo; Shuya Mitoma; Tamaki Okabayashi; Hirohisa Mekata; Eslam Elhanafy; Hala El Daous; Thi Ngan Mai; Thi Huyen Nguyen; Norikazu Isoda; Yoshihiro Sakoda; Junzo Norimine; Satoshi Sekiguchi
    The Journal of veterinary medical science, 81, 10, 1450, 1454, 2019年10月18日, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌), Bovine viral diarrhea virus (BVDV) footprint has spread across the globe and is responsible for one of the most economically important diseases in cattle. In Japan, some regional surveillance and preventive measures to control bovine viral diarrhea (BVD) have been implemented. However, BVDV infection is poorly understood in cattle industries, and there is no systematic BVD surveillance system and control program. Kyushu is the center for raising beef cattle in Japan. Therefore, this study aimed to determine the BVDV infection using a slaughterhouse survey among beef cattle in Kyushu, Japan. A total of 1,075 blood samples were collected at two regional slaughterhouses in Miyazaki prefecture from December 2015 to June 2016. Antigen ELISA was used for detection of BVDV antigen in blood samples. Two samples showed positive results (2/1,075; 0.18%). BVDV RNA was extracted from positive blood samples; the sequence was determined and analyzed by the neighbor-joining method for construction of the phylogenetic tree. Phylogenetic analysis based on the 5'-UTR revealed that the two positive samples were grouped into the same subtype BVDV-1b in the BVDV-1 genotype, but the infected cattle belonged to two different farms. In conclusion, this is the first study to identify the presence of BVDV in a slaughterhouse survey in Kyushu. These findings suggest that a slaughterhouse survey is a useful tool for developing a surveillance system for monitoring infectious diseases in cattle.
  • The first isolation and identification of canine parvovirus (CPV) type 2c variants during 2016-2018 genetic surveillance of dogs in Mongolia.
    Uyangaa Temuujin; Ariunaa Tserendorj; Jumpei Fujiki; Yoshihiro Sakoda; Erdene-Ochir Tseren-Ochir; Masatoshi Okamatsu; Keita Matsuno; Tumenjargal Sharav; Motohiro Horiuchi; Takashi Umemura; Tungalag Chultemdorj
    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 73, 269, 275, 2019年09月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Canine parvovirus type 2 (CPV-2) causes a highly contagious and fatal disease, developing into acute hemorrhagic enteritis and myocarditis, in dogs. CPV-2 has evolved, generating antigenic variants CPV-2a/2b/2c that are globally distributed. However, investigating molecular characterization of CPV-2 among dog populations in Mongolia has been limited. Herein, 42 stool samples were collected from dogs with clinical signs of infection, and conventional PCR assays were employed to detect CPV-2 in 23. Our results indicated that during 2016-2018, the new CPV-2a and 2c subtypes were detected in 34.7% of the samples, and the new CPV-2b subtype was detected in 30.4% of samples. VP2 protein sequence analysis and next-generation sequencing of the complete viral genome confirmed these antigenic types. However, sequence analysis indicated new and unreported mutations, Pro580Thr, and Tyr584His in the CPV-2c subtype. From a PCR-positive sample, CPV-2c was successfully isolated, and we performed an immunofluorescence assay for antigen detection. Additionally, we performed genetic characterization and phylogenetic analysis to investigate genetic diversity among isolates from the region, resulting in high CPV-2 genetic diversity in the Mongolian dog population. Striking similarities were also observed between sequences of the strains isolated from Mongolia and China over a similar time span.
  • Glycan-immobilized dual-channel field effect transistor biosensor for the rapid identification of pandemic influenza viral particles.
    Sho Hideshima; Hiroki Hayashi; Hiroshi Hinou; Shunsuke Nambuya; Shigeki Kuroiwa; Takuya Nakanishi; Toshiyuki Momma; Shin-Ichiro Nishimura; Yoshihiro Sakoda; Tetsuya Osaka
    Scientific reports, 9, 1, 11616, 11616, 2019年08月12日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Pandemic influenza, triggered by the mutation of a highly pathogenic avian influenza virus (IFV), has caused considerable damage to public health. In order to identify such pandemic IFVs, antibodies that specifically recognize viral surface proteins have been widely used. However, since the analysis of a newly discovered virus is time consuming, this delays the availability of suitable detection antibodies, making this approach unsuitable for the early identification of pandemic IFVs. Here we propose a label-free semiconductor-based biosensor functionalized with sialic-acid-containing glycans for the rapid identification of the pandemic IFVs present in biological fluids. Specific glycans are able to recognize wild-type human and avian IFVs, suggesting that they are useful in discovering pandemic IFVs at the early stages of an outbreak. We successfully demonstrated that a dual-channel integrated FET biosensing system, which were modified with 6'-sialyllactose and 3'-sialyllactose for each gate area, can directly and specifically detect human H1N1 and avian H5N1 IFV particles, respectively, present in nasal mucus. Furthermore, to examine the possibility of identifying pandemic IFVs, the signal attributed to the detection of Newcastle disease virus (NDV) particles, which was selected as a prime model of a pandemic IFV, was clearly observed from both sensing gates. Our findings suggest that the proposed glycan-immobilized sensing system could be useful in identifying new pandemic IFVs at the source of an outbreak.
  • A systematic study towards evolutionary and epidemiological dynamics of currently predominant H5 highly pathogenic avian influenza viruses in Vietnam.
    Nguyen LT; Firestone SM; Stevenson MA; Young ND; Sims LD; Chu DH; Nguyen TN; Van Nguyen L; Thanh Le T; Van Nguyen H; Nguyen HN; Tien TN; Nguyen TD; Tran BN; Matsuno K; Okamatsu M; Kida H; Sakoda Y
    Scientific reports, 9, 1, 7723, 7723, 2019年05月22日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), This study aimed to elucidate virus, host and environmental dynamics of Vietnamese H5 highly pathogenic avian influenza viruses (HPAIVs) during 2014-2017. Epidemiologically, H5 HPAIVs were frequently detected in apparently healthy domestic and Muscovy ducks and therefore these are preferred species for H5 HPAIV detection in active surveillance. Virologically, clade 2.3.2.1c and 2.3.4.4 H5 HPAIVs were predominant and exhibited distinct phylogeographic evolution. Clade 2.3.2.1c viruses clustered phylogenetically in North, Central and South regions, whilst clade 2.3.4.4 viruses only detected in North and Central regions formed small groups. These viruses underwent diverse reassortment with existence of at least 12 genotypes and retained typical avian-specific motifs. These H5 HPAIVs exhibited large antigenic distance from progenitor viruses and commercial vaccines currently used in poultry. Bayesian phylodynamic analysis inferred that clade 2.3.2.1c viruses detected during 2014-2017 were likely descended from homologous clade viruses imported to Vietnam previously and/or preexisting Chinese viruses during 2012-2013. Vietnamese clade 2.3.4.4 viruses closely shared genetic traits with contemporary foreign spillovers, suggesting that there existed multiple transboundary virus dispersals to Vietnam. This study provides insights into the evolution of Vietnamese H5 HPAIVs and highlights the necessity of strengthening control measures such as, preventive surveillance and poultry vaccination.
  • Assessment of the cost effectiveness of compulsory testing of introduced animals and bulk tank milk testing for bovine viral diarrhea in Japan.
    Isoda N; Asano A; Ichijo M; Ohno H; Sato K; Okamoto H; Nakao S; Kato H; Saito K; Ito N; Usui A; Takayama H; Sakoda Y
    The Journal of veterinary medical science, 81, 4, 577, 585, 2019年04月16日, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌), Bovine viral diarrhea (BVD) is a chronic disease of cattle caused by infection with BVD virus (BVDV) and can result in economic losses within the livestock industry. In Japan, the test and culling policy is a basic control measure, and implementation of an adequate vaccination program is recommended as a national policy. In addition, optional control measures, including compulsory testing of introduced animals and bulk tank milk (BTM) testing as a mass screening method, are used in several provinces, but their efficacy has not been completely assessed. We evaluated these control measures using the scenario tree model of BVD in Japan, developed in the previous study. The model outputs indicated that compulsory testing of all introduced cattle, rather than only heifers and/or non-vaccinated cattle, was cost effective and reduced the risk of BVDV introduction due to animal movement and that BTM testing could effectively monitor most part of the cattle population. Vaccination coverage and BVDV prevalence among introduced cattle could also affect the cost effectiveness of compulsory testing of targeted cattle, particularly under low vaccination coverage or high BVDV prevalence. However, even with the implementation of a highly effective monitoring scheme for many years, BVD risk could not be eliminated; it instead converged at a very low level (0.02%). Disease models with a cost-effective output could be a powerful tool in developing a control scheme for chronic animal diseases, including BVD, with the consent of relevant stakeholders.
  • Characterization of a novel reassortant H7N3 highly pathogenic avian influenza virus isolated from a poultry meat product taken on a passenger flight to Japan.
    Shibata A; Harada R; Okamatsu M; Matsuno K; Arita T; Suzuki Y; Shirakura M; Odagiri T; Takemae N; Uchida Y; Saito T; Sakoda Y; Osaka H
    The Journal of veterinary medical science, 81, 3, 444, 448, 2019年03月20日, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌), A new reassortant H7N3 avian influenza virus (AIV) was isolated from a duck meat product that was illegally taken on board a passenger flight from China to Japan in March 2018. Sequencing analysis revealed that the H7N3 isolate, A/duck/Japan/AQ-HE30-1/2018 (Dk/HE30-1) (H7N3), was a reassortant highly pathogenic avian influenza virus (HPAIV) that contained the haemagglutinin (HA) gene of Chinese H7N9 HPAIV. Dk/HE30-1 (H7N3) possessed a novel polybasic sequence motif PEVPKRRRTAR/GLF at the HA cleavage site that has never previously been reported in H7 HPAIVs. The HA antigenicity of Dk/HE30-1 (H7N3) slightly differed from that of H7N9 HPAIVs previously reported. These findings will help further our knowledge of the circulation and genetic evolution of emerging AIVs in endemic areas.
  • Inhibition of avian-origin influenza A(H7N9) virus by the novel cap-dependent endonuclease inhibitor baloxavir marboxil.
    Taniguchi K; Ando Y; Nobori H; Toba S; Noshi T; Kobayashi M; Kawai M; Yoshida R; Sato A; Shishido T; Naito A; Matsuno K; Okamatsu M; Sakoda Y; Kida H
    Scientific reports, 9, 1, 3466, 3466, 2019年03月05日, [査読有り], [国際誌]
    英語, Human infections with avian-origin influenza A(H7N9) virus represent a serious threat to global health; however, treatment options are limited. Here, we show the inhibitory effects of baloxavir acid (BXA) and its prodrug baloxavir marboxil (BXM), a first-in-class cap-dependent endonuclease inhibitor, against A(H7N9), in vitro and in vivo. In cell culture, BXA at four nanomolar concentration achieved a 1.5-2.8 log reduction in virus titers of A(H7N9), including the NA-R292K mutant virus and highly pathogenic avian influenza viruses, whereas NA inhibitors or favipiravir required approximately 20-fold or higher concentrations to achieve the same levels of reduction. A(H7N9)-specific amino acid polymorphism at position 37, implicated in BXA binding to the PA endonuclease domain, did not impact on BXA susceptibility. In mice, oral administration of BXM at 5 and 50 mg/kg twice a day for 5 days completely protected from a lethal A/Anhui/1/2013 (H7N9) challenge, and reduced virus titers more than 2-3 log in the lungs. Furthermore, the potent therapeutic effects of BXM in mice were still observed when a higher virus dose was administered or treatment was delayed up to 48 hours post infection. These findings support further investigation of BXM for A(H7N9) treatment in humans.
  • Evaluation of a rapid isothermal nucleic acid amplification kit, Alere™ i Influenza A&B, for the detection of avian influenza viruses.
    Bazarragchaa E; Okamatsu M; Ulaankhuu A; Twabela AT; Matsuno K; Kida H; Sakoda Y
    Journal of virological methods, 265, 121, 125, 2019年03月, [査読有り], [国際誌]
    英語, Rapid and accurate diagnosis of influenza virus infection is essential for quick responses for both human and animal health. The Alere™ i Influenza A&B is a novel isothermal nucleic acid amplification kit that can detect and differentiate between influenza A and B viruses in human specimens in approximately 15 min. In the present study, the performance of the Alere™ i Influenza A&B kit was evaluated for its ability to detect avian influenza virus in chickens. The kit was able to detect representative avian influenza virus strains (hemagglutinin subtypes H1-H16, including the recently isolated H5 and H7 highly pathogenic avian influenza viruses), and the detection limit of the kit for these viruses varied between 10-1.4-102.1 50% egg-infective dose per test, which is higher than the analytical sensitivity of the antigen detection immunochromatography kit ESPLINE® A INFLUENZA. In experimentally infected chickens inoculated with a highly pathogenic avian influenza virus strain A/chicken/Hokkaido/002/2016 (H5N6), viral RNA was detected in the tracheal and cloacal swabs. These results indicate that this kit has the potential to be used as a rapid screening test of influenza A virus infection in chickens.
  • Infection of newly identified phleboviruses in ticks and wild animals in Hokkaido, Japan indicating tick-borne life cycles.
    Shiho Torii; Keita Matsuno; Yongjin Qiu; Akina Mori-Kajihara; Masahiro Kajihara; Ryo Nakao; Naganori Nao; Katsunori Okazaki; Mariko Sashika; Takahiro Hiono; Masatoshi Okamatsu; Yoshihiro Sakoda; Hideki Ebihara; Ayato Takada; Hirofumi Sawa
    Ticks and tick-borne diseases, 10, 2, 328, 335, 2019年02月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), 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.
  • Lectin microarray analyses reveal host cell-specific glycan profiles of the hemagglutinins of influenza A viruses.
    Hiono T; Matsuda A; Wagatsuma T; Okamatsu M; Sakoda Y; Kuno A
    Virology, 527, 132, 140, 2019年01月15日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), 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.
  • Glycans in infection and immunity
    Takashi Suzuki; Masatoshi Okamatsu; Yoshihiro Sakoda; Taroh Kinoshita; Takane Katayama; Hiroshi Kiyono; Yoshiyuki Goto; Kaoru Takegawa; Naoaki Yokoyama; Yukari Fujimoto; Takashi Angata; Katsuki Ohtani; Nobutaka Wakamiya; Hisashi Arase; Shoko Nishihara; Yasuo Suda
    Glycoscience: Basic Science to Applications: Insights from the Japan Consortium for Glycobiology and Glycotechnology (JCGG), 227, 257, 2019年01月01日
    論文集(書籍)内論文
  • In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit.
    Noshi T; Kitano M; Taniguchi K; Yamamoto A; Omoto S; Baba K; Hashimoto T; Ishida K; Kushima Y; Hattori K; Kawai M; Yoshida R; Kobayashi M; Yoshinaga T; Sato A; Okamatsu M; Sakoda Y; Kida H; Shishido T; Naito A
    Antiviral research, 160, 109, 117, 2018年12月, [査読有り], [国際誌]
    英語, Cap-dependent endonuclease (CEN) resides in the PA subunit of the influenza virus and mediates the critical "cap-snatching" step of viral RNA transcription, which is considered to be a promising anti-influenza target. Here, we describe in vitro characterization of a novel CEN inhibitor, baloxavir acid (BXA), the active form of baloxavir marboxil (BXM). BXA inhibits viral RNA transcription via selective inhibition of CEN activity in enzymatic assays, and inhibits viral replication in infected cells without cytotoxicity in cytopathic effect assays. The antiviral activity of BXA is also confirmed in yield reduction assays with seasonal type A and B viruses, including neuraminidase inhibitor-resistant strains. Furthermore, BXA shows broad potency against various subtypes of influenza A viruses (H1N2, H5N1, H5N2, H5N6, H7N9 and H9N2). Additionally, serial passages of the viruses in the presence of BXA result in isolation of PA/I38T variants with reduced BXA susceptibility. Phenotypic and genotypic analyses with reverse genetics demonstrate the mechanism of BXA action via CEN inhibition in infected cells. These results reveal the in vitro characteristics of BXA and support clinical use of BXM to treat influenza.
  • Repeated detection of H7N9 avian influenza viruses in raw poultry meat illegally brought to Japan by international flight passengers.
    Akihiro Shibata; Masatoshi Okamatsu; Riho Sumiyoshi; Keita Matsuno; Zu-Jyun Wang; Hiroshi Kida; Hiroyuki Osaka; Yoshihiro Sakoda
    Virology, 524, 10, 17, 2018年11月, [査読有り], [国際誌]
    英語, H7N9 highly and low pathogenic avian influenza viruses (HPAIV and LPAIV, respectively) have been isolated from duck meat products that were brought illegally into Japan by flight passengers in their hand luggage. These H7N9 virus isolates were phylogenetically closely related to those prevailing in China. Antigenic analysis revealed that the hemagglutinin of the H7N9 HPAIV isolate was slightly different from those of the H7N9 LPAIV and older H7 strains. These meat products contaminated with AIVs repeatedly brought into Japan lead to increased risks of poultry and public health. Continuous border disease control based on the detection and culling of infected poultry and meat products is, thus, essential for the prevention of introduction and spread of AIVs.
  • Fatal Tickborne Phlebovirus Infection in Captive Cheetahs, Japan.
    Keita Matsuno; Noriyuki Nonoue; Ayako Noda; Nodoka Kasajima; Keita Noguchi; Ai Takano; Hiroshi Shimoda; Yasuko Orba; Mieko Muramatsu; Yoshihiro Sakoda; Ayato Takada; Shinji Minami; Yumi Une; Shigeru Morikawa; Ken Maeda
    Emerging infectious diseases, 24, 9, 1726, 1729, 2018年09月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Two captive cheetahs from a zoo in Japan died of a severe fever with thrombocytopenia syndrome-like illness. Severe fever with thrombocytopenia syndrome virus, an endemic tickborne phlebovirus, was detected systemically with secretion of infectious viruses into the saliva. These cases highlight the risk for exposure of captive animals to endemic arthropodborne pathogens.
  • H13 influenza viruses in wild birds have undergone genetic and antigenic diversification in nature.
    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], [国際誌]
    英語, 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.
  • Highly Pathogenic Avian Influenza A(H5N8) Virus, Democratic Republic of the Congo, 2017.
    Twabela AT; Tshilenge GM; Sakoda Y; Okamatsu M; Bushu E; Kone P; Wiersma L; Zamperin G; Drago A; Zecchin B; Monne I
    Emerging infectious diseases, 24, 7, 1371, 1374, 2018年07月, [査読有り]
  • Isolation and characterization of avian influenza viruses from raw poultry products illegally imported to Japan by international flight passengers
    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, Blackwell Publishing Ltd, 2018年04月01日, [査読有り]
    英語, 研究論文(学術雑誌)
  • Evaluation of bovine viral diarrhoea virus control strategies in dairy herds in Hokkaido, Japan, using stochastic modelling
    S. Sekiguchi; P. Presi; R. Omori; K. Staerk; M. Schuppers; N. Isoda; Y. Yoshikawa; T. Umemura; H. Nakayama; Y. Fujii; Y. Sakoda
    Transboundary and Emerging Diseases, 65, 1, e135, e144, Blackwell Publishing Ltd, 2018年02月01日, [査読有り]
    英語, 研究論文(学術雑誌)
  • Prevalence of hobi-like viruses in Japan between 2012 and 2017 based on virological methods and serology
    Takashi Kozasa; Shiho Torii; Ken Ichiro Kameyama; Makoto Nagai; Norikazu Isoda; Mai Shiokawa; Hiroshi Aoki; Masatoshi Okamatsu; Hideto Sekiguchi; Akito Saito; Yoshihiro Sakoda
    Japanese Journal of Veterinary Research, 66, 4, 317, 324, 2018年
    研究論文(学術雑誌)
  • Toll-like receptor 3 in nasal CD103 + dendritic cells is involved in immunoglobulin A production
    H. Takaki; S. Kure; H. Oshiumi; Y. Sakoda; T. Suzuki; A. Ainai; H. Hasegawa; M. Matsumoto; T. Seya
    Mucosal Immunology, 11, 1, 82, 96, Nature Publishing Group, 2018年01月01日, [査読有り]
    英語, 研究論文(学術雑誌)
  • Potency of an inactivated influenza vaccine prepared from A/duck/Mongolia/245/2015 (H10N3) against H10 influenza virus infection in a mouse model
    Mizuho Suzuki; Masatoshi Okamatsu; Yuri Fujimoto; Takahiro Hiono; Keita Matsuno; Hiroshi Kida; Yoshihiro Sakoda
    Japanese Journal of Veterinary Research, 66, 1, 29, 41, Hokkaido University, 2018年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Characterization of recombinant Flaviviridae viruses possessing a small reporter Tag
    Tomokazu Tamura; Takasuke Fukuhara; Takuro Uchida; Chikako Ono; Hiroyuki Mori; Asuka Sato; Yuzy Fauzyah; Toru Okamoto; Takeshi Kurosu; Yin Xiang Setoh; Michio Imamura; Norbert Tautz; Yoshihiro Sakoda; Alexander A. Khromykh; Kazuaki Chayama; Yoshiharu Matsuura
    Journal of Virology, 92, 2, American Society for Microbiology, 2018年01月01日, [査読有り]
    英語, 研究論文(学術雑誌)
  • A cross-sectional study to quantify the prevalence of avian influenza viruses in poultry at intervention and non-intervention live bird markets in central Vietnam, 2014
    D. -H. Chu; M. A. Stevenson; L. V. Nguyen; N. Isoda; S. M. Firestone; T. N. Nguyen; L. T. Nguyen; K. Matsuno; M. Okamatsu; H. Kida; Y. Sakoda
    TRANSBOUNDARY AND EMERGING DISEASES, 64, 6, 1991, 1999, 2017年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Potency of an inactivated influenza vaccine prepared from A/duck/Hokkaido/162/2013 (H2N1) against a challenge with A/swine/Missouri/2124514/2006 (H2N3) in mice
    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]
    英語, 研究論文(学術雑誌)
  • Detection and molecular characterization of equine infectious anemia virus in Mongolian horses
    Tumenjargal Sharav; Satoru Konnai; Nyamsuren Ochirkhuu; Erdene T. S. Ochir; Hirohisa Mekata; Yoshihiro Sakoda; Takashi Umemura; Shiro Murata; Tungalag Chultemdorj; Kazuhiko Ohashi
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 79, 11, 1884, 1888, 2017年11月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Selection of antigenic variants of an H5N1 highly pathogenic avian influenza virus in vaccinated chickens
    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]
    英語, 研究論文(学術雑誌)
  • Engineering of Small Reporter-Tagged Flaviviridae Viruses Applicable to Antiviral Screening and in vivo Dynamics
    Tomokazu Tamura; Takasuke Fukuhara; Akatuski Saito; Takuro Uchida; Chikako Ono; Hiroyuki Mori; Toru Okamoto; Takeshi Kurosu; Norbert Tautz; Yoshihiro Sakoda; Tatuso Shioda; Kazuaki Chayama; Yoshiharu Matsuura
    2017年09月
    英語, 研究論文(国際会議プロシーディングス)
  • Characterization of H5N6 highly pathogenic avian influenza viruses isolated from wild and captive birds in the winter season of 2016-2017 in Northern Japan
    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]
    英語, 研究論文(学術雑誌)
  • Genetic characterization of an H2N2 influenza virus isolated from a muskrat in Western Siberia
    Marina Gulyaeva; Kirill Sharshov; Mizuho Suzuki; Ivan Sobolev; Yoshihiro Sakoda; Alexander Alekseev; Mariya Sivay; Lidia Shestopalova; Michael Shchelkanov; Alexander Shestopalov
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 79, 8, 1461, 1465, 2017年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Rapid and broad detection of H5 hemagglutinin by an immunochromatographic kit using novel monoclonal antibody against highly pathogenic avian influenza virus belonging to the genetic clade 2.3.4.4
    Lam Thanh Nguyen; Kazunari Nakaishi; Keiko Motojima; Ayako Ohkawara; Erina Minato; Junki Maruyama; Takahiro Hiono; Keita Matsuno; Masatoshi Okamatsu; Takashi Kimura; Ayato Takada; Hiroshi Kida; Yoshihiro Sakoda
    PLOS ONE, 12, 8, e0182228, 2017年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Evaluation of control measures for bovine viral diarrhea implemented in Nemuro District, Hokkaido, Japan, using a scenario tree model
    Norikazu Isoda; Akihiro Asano; Michiru Ichijo; Shiho Wakamori; Hiroshi Ohno; Kazuhiko Sato; Hirokazu Okamoto; Shigeru Nakao; Hajime Kato; Kazuma Saito; Naoki Ito; Akira Usui; Hiroaki Takayama; Yoshihiro Sakoda
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 79, 7, 1172, 1181, 2017年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Host-derived apolipoproteins play comparable roles with viral secretory proteins E-rns and NS1 in the infectious particle formation of Flaviviridae
    Takasuke Fukuhara; Tomokazu Tamura; Chikako Ono; Mai Shiokawa; Hiroyuki Mori; Kentaro Uemura; Satomi Yamamoto; Takeshi Kurihara; Toru Okamoto; Ryosuke Suzuki; Kentaro Yoshii; Takeshi Kurosu; Manabu Igarashi; Hiroshi Aoki; Yoshihiro Sakoda; Yoshiharu Matsuura
    PLOS PATHOGENS, 13, 6, e1006475, 2017年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Genetic and virulence characterization of classical swine fever viruses isolated in Mongolia from 2007 to 2015
    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]
    英語, 研究論文(学術雑誌)
  • Antigenic diversity of H5 highly pathogenic avian influenza viruses of clade 2.3.4.4 isolated in Asia
    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]
    英語, 研究論文(学術雑誌)
  • Potency of whole virus particle and split virion vaccines using dissolving microneedle against challenges of H1N1 and H5N1 influenza viruses in mice
    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]
    英語, 研究論文(学術雑誌)
  • Characterization of Highly Pathogenic Avian Influenza Virus A(H5N6), Japan, November 2016
    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]
    英語, 研究論文(学術雑誌)
  • Therapeutic efficacy of peramivir against H5N1 highly pathogenic avian influenza viruses harboring the neuraminidase H275Y mutation
    Masanori Kobayashi; Makoto Kodama; Takeshi Noshi; Ryu Yoshida; Takushi Kanazu; Naoki Nomura; Kosuke Soda; Norikazu Isoda; Masatoshi Okamatsu; Yoshihiro Sakoda; Yoshinori Yamano; Akihiko Sato; Hiroshi Kida
    ANTIVIRAL RESEARCH, 139, 41, 48, 2017年03月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Potential risk of repeated nasal vaccination that induces allergic reaction with mucosal IgE and airway eosinophilic infiltration in cynomolgus macaques infected with H5N1 highly pathogenic avian influenza virus
    Misako Nakayama; Yasushi Itoh; Shintaro Shichinohe; Rumi Nakabayashi; Hirohito Ishigaki; Yoshihiro Sakoda; Quynh Mai Le; Yoshihiro Kawaoka; Hiroshi Kida; Kazumasa Ogasawara
    VACCINE, 35, 7, 1008, 1017, 2017年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Host-derived apolipoproteins play comparable roles with viral secretory proteins Ernsand NS1 in the infectious particle formation of Flaviviridae
    Takasuke Fukuhara; Tomokazu Tamura; Chikako Ono; Mai Shiokawa; Hiroyuki Mori; Kentaro Uemura; Satomi Yamamoto; Takeshi Kurihara; Toru Okamoto; Ryosuke Suzuki; Kentaro Yoshii; Takeshi Kurosu; Manabu Igarashi; Hiroshi Aoki; Yoshihiro Sakoda; Yoshiharu Matsuura
    PLoS Pathogens, 13, 6, Public Library of Science, 2017年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection
    Misako Nakayama; Hiroichi Ozaki; Yasushi Itoh; Kosuke Soda; Hirohito Ishigaki; Masatoshi Okamatsu; Yoshihiro Sakoda; Chun-Ho Park; Hideaki Tsuchiya; Hiroshi Kida; Kazumasa Ogasawara
    PATHOLOGY INTERNATIONAL, 66, 12, 678, 686, 2016年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus
    Fumihiko Yasui; Yasushi Itoh; Ai Ikejiri; Masahiro Kitabatake; Nobuo Sakaguchi; Keisuke Munekata; Shintaro Shichinohe; Yukiko Hayashi; Hirohito Ishigaki; Misako Nakayama; Yoshihiro Sakoda; Hiroshi Kida; Kazumasa Ogasawara; Michinori Kohara
    SCIENTIFIC REPORTS, 6, 37915, 2016年11月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Role for migratory wild birds in the global spread of avian influenza H5N8
    Samantha J. Lycett; Rogier Bodewes; Anne Pohlmann; Jill Banks; Krisztian Banyai; Maciej F. Boni; Ruth Bouwstra; Andrew C. Breed; Ian H. Brown; Hualan Chen; Adam Dan; Thomas J. DeLiberto; Nguyen Diep; Marius Gilbert; Sarah Hill; Hon S. Ip; Chang Wen Ke; Hiroshi Kida; Mary Lea Killian; Marion P. Koopmans; Jung-Hoon Kwon; Dong-Hun Lee; Youn Jeong Lee; Lu Lu; Isabella Monne; John Pasick; Oliver G. Pybus; Andrew Rambaut; Timothy P. Robinson; Yoshihiro Sakoda; Siamak Zohari; Chang-Seon Song; David E. Swayne; Mia Kim Torchetti; Hsiang-Jung Tsai; Ron A. M. Fouchier; Martin Beer; Mark Woolhouse; Thijs Kuiken
    SCIENCE, 354, 6309, 213, 217, 2016年10月, [査読有り]
    英語, 研究論文(学術雑誌)
  • フラビウイルス科ウイルスの粒子産生における分泌性糖タンパク質の役割
    Tomokazu Tamura; Takasuke Fukuhara; Mai Shiokawa; Chikako Ono; Satomi Yamamoto; Hiroyuki Mori; Takeshi Kurihara; Toru Okamoto; Hiroshi Aoki; Yoshihiro Sakoda; Yoshiharu Matsuura
    2016年10月
    日本語, 研究論文(その他学術会議資料等)
  • The roles of secretory glycoproteins in viral particle formation in family Flaviviridae
    Tomokazu Tamura; Takasuke Fukuhara; Mai Shiokawa; Chikako Ono; Satomi Yamamoto; Hiroyuki Mori; Takeshi Kurihara; Toru Okamoto; Hiroshi Aoki; Yoshihiro Sakoda; Yoshiharu Matsuura
    2016年10月, [査読有り]
    英語, 研究論文(その他学術会議資料等)
  • Viral secretory glycoproteins of Flaviviridae virus have similar roles with apolipoproteins on the formation of infectious HCV particles
    Takasuke Fukuhara; Tomokazu Tamura; Mai Shiokawa; Chikako Ono; Satomi Yamamoto; Hiroyuki Mori; Takeshi Kurihara; Kentaro Uemura; Toru Okamoto; Hiroshi Aoki; Yoshihiro Sakoda; Yoshiharu Matsuura
    2016年10月, [査読有り]
    英語, 研究論文(その他学術会議資料等)
  • Nationwide Distribution of Bovine Influenza D Virus Infection in Japan
    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]
    英語, 研究論文(学術雑誌)
  • Recent developments in the diagnosis of avian influenza
    Masatoshi Okamatsu; Takahiro Hiono; Hiroshi Kida; Yoshihiro Sakoda
    VETERINARY JOURNAL, 215, 82, 86, 2016年09月, [査読有り]
    英語
  • Genetic and antigenic characterization of H5, H6 and H9 avian influenza viruses circulating in live bird markets with intervention in the center part of Vietnam
    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]
    英語, 研究論文(学術雑誌)
  • Isolation of a sp nov Ljungan virus from wild birds in Japan
    Hiromichi Mitake; Yuji Fujii; Makoto Nagai; Naoto Ito; Kota Okadera; Kazuma Okada; Kento Nakagawa; Mai Kishimoto; Tetsuya Mizutani; Katsunori Okazaki; Yoshihiro Sakoda; Ayato Takada; Makoto Sugiyama
    JOURNAL OF GENERAL VIROLOGY, 97, 8, 1818, 1822, 2016年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Is the optimal pH for membrane fusion in host cells by avian influenza viruses related to host range and pathogenicity?
    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]
    英語, 研究論文(学術雑誌)
  • Comparison of pathogenicities of H7 avian influenza viruses via intranasal and conjunctival inoculation in cynomolgus macaques
    Shintaro Shichinohe; Yasushi Itoh; Misako Nakayama; Hiroichi Ozaki; Kosuke Soda; Hirohito Ishigaki; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Kazumasa Ogasawara
    VIROLOGY, 493, 31, 38, 2016年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Toll-like receptor 9 ligand D-type oligodeoxynucleotide D35 as a broad inhibitor for influenza A virus replication that is associated with suppression of neuraminidase activity
    Hiroshi Yamada; Satoshi Nagase; Kazuo Takahashi; Yoshihiro Sakoda; Hiroshi Kida; Shigefumi Okamoto
    ANTIVIRAL RESEARCH, 129, 81, 92, 2016年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Evaluation of truncated LipL32 expressed by Escherichia coli and Pichia pastoris for serodiagnosis of Leptospira infection in rodents
    Kanae Shiokawa; Chandika D. Gamage; Nobuo Koizumi; Yoshihiro Sakoda; Kenta Shimizu; Yoshimi Tsuda; Kumiko Yoshimatsu; Jiro Arikawa
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 78, 2, 221, 230, 2016年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Amino acid residues at positions 222 and 227 of the hemagglutinin together with the neuraminidase determine binding of H5 avian influenza viruses to sialyl Lewis X
    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]
    英語, 研究論文(学術雑誌)
  • Complete genome sequence of the avian paramyxovirus serotype 5 strain APMV-5/budgerigar/Japan/TI/75
    Takahiro Hiono; Keita Matsuno; Kotaro Tuchiya; Zhifeng Lin; Masatoshi Okamatsu; Yoshihiro Sakoda
    Genome Announcements, 4, 5, American Society for Microbiology, 2016年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Experimental infection of highly and low pathogenic avian influenza viruses to chicken's, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission
    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]
    英語, 研究論文(学術雑誌)
  • Genetic and antigenic characterization of bovine viral diarrhea viruses isolated from cattle in Hokkaido, Japan
    Yuri Abe; Tomokazu Tamura; Shiho Torii; Shiho Wakamori; Makoto Nagai; Kazuya Mitsuhashi; Junki Mine; Yuri Fujimoto; Naofumi Nagashima; Fumi Yoshino; Yukihiko Sugita; Takushi Nomura; Masatoshi Okamatsu; Hiroshi Kida; Yoshihiro Sakoda
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 78, 1, 61, 70, 2016年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Protective efficacy of stockpiled vaccine against H5N8 highly pathogenic avian influenza virus isolated from a chicken in Kumamoto prefecture, Japan, in 2014
    Koichiro Gamoh; Mari Nakamizo; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Shoko Suzuki
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 78, 1, 139, 142, 2016年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Intracellular membrane association of classical swine fever virus NS4B is critical for viral RNA replication
    Tomokazu Tamura; Nicolas Ruggli; Masatoshi Okamatsu; Keita Matsuno; Yoshihiro Sakoda
    2015年11月, [査読有り]
    日本語, 研究論文(その他学術会議資料等)
  • 豚コレラウイルスの病原性発現の分子基盤
    田村友和; Nicolas Ruggli; 岡松正敏; 松野啓太; 迫田義博
    2015年11月, [査読有り]
    日本語, 研究論文(その他学術会議資料等)
  • Apolipoproteins and viral secretory glycoproteins participate in the infectious particle formation of Flaviviridae
    Takasuke Fukuhara; Tomokazu Tamura; Mai Shiokawa; Chikako Ono; Satomi Yamamoto; Hiroyuki Mori; Takeshi Kurihara; Toru Okamoto; Hiroshi Aoki; Yoshihiro Sakoda; Yoshiharu Matsuura
    2015年11月, [査読有り]
    英語, 研究論文(その他学術会議資料等)
  • フラビウイルス科に共通した小胞体膜結合因子を介した粒子産生機構の解析
    福原 崇介; 田村 友和; 塩川 舞; 小野 慎子; 山本 聡美; 森 寛行; 栗原 健; 岡本 徹; 青木 博史; 迫田 義博; 松浦 善治
    2015年11月, [査読有り]
    日本語, 研究論文(その他学術会議資料等)
  • Host or virus derived secretory membrane binding proteins are involved in formation of infectious Flavivirus particles
    Takasuke Fukuhara; Tomokazu Tamura; Mai Shiokawa; Chikako Ono; Satomi Yamamoto; Hiroyuki Mori; Takeshi Kurihara; Puig-Basagoiti Francesc; Toru Okamoto; Hiroshi Aoki; Yoshihiro Sakoda; Yoshiharu Matsuura
    2015年11月, [査読有り]
    英語, 研究論文(その他学術会議資料等)
  • A Single Amino Acid in the M1 Protein Responsible for the Different Pathogenic Potentials of H5N1 Highly Pathogenic Avian Influenza Virus Strains
    Naganori Nao; Masahiro Kajihara; Rashid Manzoor; Junki Maruyama; Reiko Yoshida; Mieko Muramatsu; Hiroko Miyamoto; Manabu Igarashi; Nao Eguchi; Masahiro Sato; Tatsunari Kondoh; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Ayato Takada
    PLOS ONE, 10, 9, e0137989, 2015年09月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Intracellular membrane association of the N-terminal domain of classical swine fever virus NS4B determines viral genome replication and virulence
    Tomokazu Tamura; Nicolas Ruggli; Naofumi Nagashima; Masatoshi Okamatsu; Manabu Igarashi; Junki Mine; Martin A. Hofmann; Matthias Liniger; Artur Summerfield; Hiroshi Kida; Yoshihiro Sakoda
    JOURNAL OF GENERAL VIROLOGY, 96, 9, 2623, 2635, 2015年09月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Genetic and antigenic characterization of H5 and H7 influenza viruses isolated from migratory water birds in Hokkaido, Japan and Mongolia from 2010 to 2014
    Takahiro Hiono; Ayako Ohkawara; Kohei Ogasawara; Masatoshi Okamatsu; Tomokazu Tamura; Duc-Huy Chu; Mizuho Suzuki; Saya Kuribayashi; Shintaro Shichinohe; Ayato Takada; Hirohito Ogawa; Reiko Yoshida; Hiroko Miyamoto; Naganori Nao; Wakako Furuyama; Junki Maruyama; Nao Eguchi; Gerelmaa Ulziibat; Bazarragchaa Enkhbold; Munkhduuren Shatar; Tserenjav Jargalsaikhan; Selenge Byambadorj; Batchuluun Damdinjav; Yoshihiro Sakoda; Hiroshi Kida
    VIRUS GENES, 51, 1, 57, 68, 2015年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Emergence of H7N9 Influenza A Virus Resistant to Neuraminidase Inhibitors in Nonhuman Primates
    Yasushi Itoh; Shintaro Shichinohe; Misako Nakayama; Manabu Igarashi; Akihiro Ishii; Hirohito Ishigaki; Hideaki Ishida; Naoko Kitagawa; Takako Sasamura; Masanori Shiohara; Michiko Doi; Hideaki Tsuchiya; Shinichiro Nakamura; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Kazumasa Ogasawara
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 59, 8, 4962, 4973, 2015年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • 豚コレラウイルス非構造蛋白NS4Bの機能と病原性に及ぼす影響
    田村友和; Nicolas Ruggli; 長島尚史; 岡松正敏; Artur Summerfield; 松野啓太; 喜田宏; 迫田義博
    2015年07月, [査読有り]
    日本語, 研究論文(その他学術会議資料等)
  • The N-terminal domain of N-pro of classical swine fever virus determines its stability and regulates type I IFN production
    Junki Mine; Tomokazu Tamura; Kazuya Mitsuhashi; Masatoshi Okamatsu; Sujira Parchariyanon; Wasana Pinyochon; Nicolas Ruggli; Jon-Duri Tratschin; Hiroshi Kida; Yoshihiro Sakoda
    JOURNAL OF GENERAL VIROLOGY, 96, 7, 1746, 1756, 2015年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • VIRAL GENETIC DETERMINANTS OF CLASSICAL SWINE FEVER VIRUS VIRULENCE
    Tomokazu Tamura; Nicolas Ruggli; Naofumi Nagashima; Masatoshi Okamatsu; Martin A. Hofmann; Hiroshi Kida; Autur Summerfield; Yoshihiro Sakoda
    2015年06月, [査読有り]
    英語, 研究論文(国際会議プロシーディングス)
  • Analysis of a pair of END+ and END- viruses derived from the same bovine viral diarrhea virus stock reveals the amino acid determinants in N-pro responsible for inhibition of type I interferon production
    Takashi Kozasa; Yuri Abe; Kazuya Mitsuhashi; Tomokazu Tamura; Hiroshi Aoki; Masatoshi Ishimaru; Shigeyuki Nakamura; Masatoshi Okamatsu; Hiroshi Kida; Yoshihiro Sakoda
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 77, 5, 511, 518, 2015年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Pathogenicity of border disease virus FNK2012-1 strain isolated from a pig in the natural host, sheep
    Tomokazu Tamura; Junki Mine; Shiho Torii; Yuri Fujimoto; Masatoshi Okamatsu; Yoshihiro Sakoda
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 77, 3, 341, 343, 2015年03月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Fluorescent Immunochromatography for Rapid and Sensitive Typing of Seasonal Influenza Viruses
    Akira Sakurai; Katsuyoshi Takayama; Namiko Nomura; Naoki Kajiwara; Masatoshi Okamatsu; Naoki Yamamoto; Tsuruki Tamura; Jitsuho Yamada; Masako Hashimoto; Yoshihiro Sakoda; Yoshihiko Suda; Yukuharu Kobayashi; Hiroshi Kida; Futoshi Shibasaki
    PLOS ONE, 10, 2, e0116715, 2015年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Field Distribution of END Phenomenon-Negative Bovine Viral Diarrhea Virus
    Kaoru Nishine; Hiroshi Aoki; Yoshihiro Sakoda; Akio Fukusho
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 76, 12, 1635, 1639, 2014年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Field Distribution of END Phenomenon-Negative Bovine Viral Diarrhea Virus
    Kaoru Nishine; Hiroshi Aoki; Yoshihiro Sakoda; Akio Fukusho
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 76, 12, 1635, 1639, 2014年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Multi-colored immunochromatography using nanobeads for rapid and sensitive typing of seasonal influenza viruses
    Akira Sakurai; Katsuyoshi Takayama; Namiko Nomura; Naoki Yamamoto; Yoshihiro Sakoda; Yukuharu Kobayashi; Hiroshi Kida; Futoshi Shibasaki
    JOURNAL OF VIROLOGICAL METHODS, 209, 62, 68, 2014年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Neuraminidase gene homology contributes to the protective activity of influenza vaccines prepared from the influenza virus library
    Ahmad M. Haredy; Hiroshi Yamada; Yoshihiro Sakoda; Masatoshi Okamatsu; Naoki Yamamoto; Takeshi Omasa; Yasuko Mori; Hiroshi Kida; Shigefumi Okamoto; Yoshinobu Okuno; Koichi Yamanishi
    JOURNAL OF GENERAL VIROLOGY, 95, Pt 11, 2365, 2371, 2014年11月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Potency of an inactivated influenza vaccine prepared from A/duck/Hong Kong/960/1980 (H6N2) against a challenge with A/duck/Vietnam/OIE-0033/2012 (H6N2) in mice
    Tatsuya Nishi; Yoshihiro Sakoda; Masatoshi Okamatsu; Hiroshi Kida
    ARCHIVES OF VIROLOGY, 159, 10, 2567, 2574, 2014年10月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Humoral Immune Response to Influenza A(H1N1)pdm2009 in Patients with Natural Infection and in Vaccine Recipients in the 2009 Pandemic
    Takuji Kumagai; Tetsuo Nakayama; Yoshinobu Okuno; Tetsuo Kase; Naoko Nishimura; Takao Ozaki; Akiko Miyata; Eitaro Suzuki; Teruo Okafuji; Takao Okafuji; Hitoshi Ochiai; Nobuo Nagata; Hiroyuki Tsutsumi; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Toshiaki Ihara
    VIRAL IMMUNOLOGY, 27, 8, 368, 374, 2014年10月, [査読有り]
    英語, 研究論文(学術雑誌)
  • The relationship between in vivo antiviral activity and pharmacokinetic parameters of peramivir in influenza virus infection model in mice
    Makoto Kodama; Ryu Yoshida; Takahiro Hasegawa; Masaaki Izawa; Mitsutaka Kitano; Kaoru Baba; Takeshi Noshi; Takahiro Seki; Kenichi Okazaki; Masakatsu Tsuji; Takushi Kanazu; Hiroshi Kamimori; Tomoyuki Homma; Masanori Kobayashi; Yoshihiro Sakoda; Hiroshi Kida; Akihiko Sato; Yoshinori Yamano
    ANTIVIRAL RESEARCH, 109, 110, 115, 2014年09月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Pathological and Immunohistochemical Findings of Natural Highly Pathogenic Avian Influenza Infection in Tufted Ducks during 2010-2011 Outbreaks in Japan
    Walied Abdo; Mohie Haridy; Yuki Katou; Minami Goto; Toshio Mizoguchi; Yoshihiro Sakoda; Hiroki Sakai; Tokuma Yanai
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 76, 9, 1285, 1290, 2014年09月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Molecular, biological, and antigenic characterization of a Border disease virus isolated from a pig during classical swine fever surveillance in Japan
    Makoto Nagai; Hiroshi Aoki; Yoshihiro Sakoda; Takashi Kozasa; Kaho Tominaga-Teshima; Junki Mine; Yuri Abe; Tomokazu Tamura; Tsubasa Kobayashi; Kaoru Nishine; Kentaro Tateishi; Yudai Suzuki; Mai Fukuhara; Keitaro Ohmori; Reiko Todaka; Kazuhiko Katayama; Tetsuya Mizutani; Shigeyuki Nakamura; Hiroshi Kida; Junsuke Shirai
    JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION, 26, 4, 547, 552, 2014年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Potency of an inactivated influenza vaccine prepared from A/duck/Mongolia/119/2008 (H7N9) against the challenge with A/Anhui/1/2013 (H7N9)
    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]
    英語, 研究論文(学術雑誌)
  • Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection
    Yasushi Itoh; Reiko Yoshida; Shintaro Shichinohe; Megumi Higuchi; Hirohito Ishigaki; Misako Nakayama; Van Loi Pham; Hideaki Ishida; Mitsutaka Kitano; Masahiko Arikata; Naoko Kitagawa; Yachiyo Mitsuishi; Kazumasa Ogasawara; Hideaki Tsuchiya; Takahiro Hiono; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Mutsumi Ito; Le Quynh Mai; Yoshihiro Kawaoka; Hiroko Miyamoto; Mari Ishijima; Manabu Igarashi; Yasuhiko Suzuki; Ayato Takada
    PLOS PATHOGENS, 10, 6, e1004192, 2014年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • A chicken influenza virus recognizes fucosylated α2,3 sialoglycan receptors on the epithelial cells lining upper respiratory tracts of chickens.
    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]
    英語, 研究論文(学術雑誌)
  • N-pro of classical swine fever virus contributes to pathogenicity in pigs by preventing type I interferon induction at local replication sites
    Tomokazu Tamura; Naofumi Nagashima; Nicolas Ruggli; Artur Summerfield; Hiroshi Kida; Yoshihiro Sakoda
    VETERINARY RESEARCH, 45, 47, 2014年04月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Characterization of the Envelope Glycoprotein of a Novel Filovirus, Lloviu Virus
    Junki Maruyama; Hiroko Miyamoto; Masahiro Kajihara; Hirohito Ogawa; Ken Maeda; Yoshihiro Sakoda; Reiko Yoshida; Ayato Takada
    JOURNAL OF VIROLOGY, 88, 1, 99, 109, 2014年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Histopathological Evaluation of the Diversity of Cells Susceptible to H5N1 Virulent Avian Influenza Virus
    Haru Ogiwara; Fumihiko Yasui; Keisuke Munekata; Asako Takagi-Kamiya; Tsubasa Munakata; Namiko Nomura; Futoshi Shibasaki; Kazuhiko Kuwahara; Nobuo Sakaguchi; Yoshihiro Sakoda; Hiroshi Kida; Michinori Kohara
    AMERICAN JOURNAL OF PATHOLOGY, 184, 1, 171, 183, 2014年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Genetic Analysis of an H5N2 Highly Pathogenic Avian Influenza Virus Isolated from a Chicken in a Live Bird Market in Northern Vietnam in 2012
    Tatsuya Nishi; Masatoshi Okamatsu; Kenji Sakurai; Huy Due Chu; Long Pham Thanh; Long van Nguyen; Nam van Hoang; Diep Nguyen Thi; Yoshihiro Sakoda; Hiroshi Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 76, 1, 85, 87, 2014年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Protection against H5N1 Highly Pathogenic Avian and Pandemic (H1N1) 2009 Influenza Virus Infection in Cynomolgus Monkeys by an Inactivated H5N1 Whole Particle Vaccine
    Misako Nakayama; Shintaro Shichinohe; Yasushi Itoh; Hirohito Ishigaki; Mitsutaka Kitano; Masahiko Arikata; Van Loi Pham; Hideaki Ishida; Naoko Kitagawa; Masatoshi Okamatsu; Yoshihiro Sakoda; Takaya Ichikawa; Hideaki Tsuchiya; Shinichiro Nakamura; Quynh Mai Le; Mutsumi Ito; Yoshihiro Kawaoka; Hiroshi Kida; Kazumasa Ogasawara
    PLOS ONE, 8, 12, e82740, 2013年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Polymerase complex with lysine at position 627 of the PB2 of influenza virus A/Hong Kong/483/97 (H5N1) efficiently transcribes and replicates virus genes in mouse cells
    Naoki Yamamoto; Yoshihiro Sakoda; Masatoshi Okamatsu; Hiroshi Kida
    VIRUS RESEARCH, 178, 2, 404, 410, 2013年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Factors responsible for pathogenicity in chickens of a low-pathogenic H7N7 avian influenza virus isolated from a feral duck
    Junki Maruyama; Masatoshi Okamatsu; Kosuke Soda; Yoshihiro Sakoda; Hiroshi Kida
    ARCHIVES OF VIROLOGY, 158, 12, 2473, 2478, 2013年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Broad-spectrum detection of H5 subtype influenza a viruses with a new fluorescent immunochromatography system
    Akira Sakurai; Katsuyoshi Takayama; Namiko Nomura; Tsubasa Munakata; Naoki Yamamoto; Tsuruki Tamura; Jitsuho Yamada; Masako Hashimoto; Kazuhiko Kuwahara; Yoshihiro Sakoda; Yoshihiko Suda; Yukuharu Kobayashi; Nobuo Sakaguchi; Hiroshi Kida; Michinori Kohara; Futoshi Shibasaki
    PLoS ONE, 8, 11, e76753, 11, 2013年11月06日, [査読有り]
    英語, 研究論文(学術雑誌)
  • The genetic and antigenic diversity of avian influenza viruses isolated from domestic ducks, muscovy ducks, and chickens in northern and southern Vietnam, 2010-2012
    Masatoshi Okamatsu; Tatsuya Nishi; Naoki Nomura; Naoki Yamamoto; Yoshihiro Sakoda; Kenji Sakurai; Huy Duc Chu; Long Pham Thanh; Long Van Nguyen; Nam Van Hoang; Tien Ngoc Tien; Reiko Yoshida; Ayato Takada; Hiroshi Kida
    VIRUS GENES, 47, 2, 317, 329, 2013年10月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Pathogenicity of Pandemic H1N1 Influenza A Virus in Immunocompromised Cynomolgus Macaques
    Van Loi Pham; Misako Nakayama; Yasushi Itoh; Hirohito Ishigaki; Mitsutaka Kitano; Masahiko Arikata; Hideaki Ishida; Naoko Kitagawa; Shintaro Shichinohe; Masatoshi Okamatsu; Yoshihiro Sakoda; Hideaki Tsuchiya; Shinichiro Nakamura; Hiroshi Kida; Kazumasa Ogasawara
    PLOS ONE, 8, 9, e75910, 2013年09月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Selection of H3 avian influenza viruses with SAα2,6Gal receptor specificity in pigs.
    Shichinohe S; Okamatsu M; Sakoda Y; Kida H
    Virology, 444, 1-2, 404, 408, 2013年09月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Characterization of H7N9 influenza A viruses isolated from humans
    Tokiko Watanabe; Maki Kiso; Satoshi Fukuyama; Noriko Nakajima; Masaki Imai; Shinya Yamada; Shin Murakami; Seiya Yamayoshi; Kiyoko Iwatsuki-Horimoto; Yoshihiro Sakoda; Emi Takashita; Ryan McBride; Takeshi Noda; Masato Hatta; Hirotaka Imai; Dongming Zhao; Noriko Kishida; Masayuki Shirakura; Robert P. de Vries; Shintaro Shichinohe; Masatoshi Okamatsu; Tomokazu Tamura; Yuriko Tomita; Naomi Fujimoto; Kazue Goto; Hiroaki Katsura; Eiryo Kawakami; Izumi Ishikawa; Shinji Watanabe; Mutsumi Ito; Yuko Sakai-Tagawa; Yukihiko Sugita; Ryuta Uraki; Reina Yamaji; Amie J. Eisfeld; Gongxun Zhong; Shufang Fan; Jihui Ping; Eileen A. Maher; Anthony Hanson; Yuko Uchida; Takehiko Saito; Makoto Ozawa; Gabriele Neumann; Hiroshi Kida; Takato Odagiri; James C. Paulson; Hideki Hasegawa; Masato Tashiro; Yoshihiro Kawaoka
    NATURE, 501, 7468, 551, +, 2013年09月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Excessive Cytokine Response to Rapid Proliferation of Highly Pathogenic Avian Influenza Viruses Leads to Fatal Systemic Capillary Leakage in Chickens
    Saya Kuribayashi; Yoshihiro Sakoda; Takeshi Kawasaki; Tomohisa Tanaka; Naoki Yamamoto; Masatoshi Okamatsu; Norikazu Isoda; Yoshimi Tsuda; Yuji Sunden; Takashi Umemura; Noriko Nakajima; Hideki Hasegawa; Hiroshi Kida
    PLOS ONE, 8, 7, e68375, 2013年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • An MDCK cell culture-derived formalin-inactivated influenza virus whole-virion vaccine from an influenza virus library confers cross-protective immunity by intranasal administration in mice
    Ahmad M. Haredy; Nobuyuki Takenaka; Hiroshi Yamada; Yoshihiro Sakoda; Masatoshi Okamatsu; Naoki Yamamoto; Takeshi Omasa; Hisao Ohtake; Yasuko Mori; Hiroshi Kida; Koichi Yamanishi; Shigefumi Okamoto
    Clinical and Vaccine Immunology, 20, 7, 998, 1007, 2013年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Proteins of duck influenza virus responsible for acquisition of pathogenicity in chickens
    Naoki Yamamoto; Kosuke Soda; Yoshihiro Sakoda; Masatoshi Okamatsu; Hiroshi Kida
    VIRUS RESEARCH, 173, 2, 294, 298, 2013年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Potency of an inactivated influenza vaccine prepared from a non-pathogenic H5N1 virus against a challenge with antigenically drifted highly pathogenic avian influenza viruses in chickens
    Shintaro Shichinohe; Masatoshi Okamatsu; Naoki Yamamoto; Yu Noda; Yuka Nomoto; Takashi Honda; Noriyasu Takikawa; Yoshihiro Sakoda; Hiroshi Kida
    VETERINARY MICROBIOLOGY, 164, 1-2, 39, 45, 2013年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Antiviral activity of stachyflin on influenza A viruses of different hemagglutinin subtypes
    Yurie Motohashi; Manabu Igarashi; Masatoshi Okamatsu; Takeshi Noshi; Yoshihiro Sakoda; Naoki Yamamoto; Kimihito Ito; Ryu Yoshida; Hiroshi Kida
    VIROLOGY JOURNAL, 10, 118, 2013年04月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Novel thiosialosides tethered to metal nanoparticles as potent influenza A virus haemagglutinin blockers.
    Feng F; Sakoda Y; Ohyanagi T; Nagahori N; Shibuya H; Okamastu M; Miura N; Kida H; Nishimura SI
    Antiviral therapy, 2013年02月, [査読有り]
  • The PB2, PA, HA, NP, and NS genes of a highly pathogenic avian influenza virus A/whooper swan/Mongolia/3/2005 (H5N1) are responsible for pathogenicity in ducks
    Masahiro Kajihara; Yoshihiro Sakoda; Kosuke Soda; Kenji Minari; Masatoshi Okamatsu; Ayato Takada; Hiroshi Kida
    VIROLOGY JOURNAL, 10, 45, 2013年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Potency of a vaccine prepared from A/swine/Hokkaido/2/1981 (H1N1) against A/Narita/1/2009 (H1N1) pandemic influenza virus strain
    Masatoshi Okamatsu; Yoshihiro Sakoda; Takahiro Hiono; Naoki Yamamoto; Hiroshi Kida
    VIROLOGY JOURNAL, 10, 47, 2013年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Fluorescence polarization-based assay using N-glycan-conjugated quantum dots for screening in hemagglutinin blockers for influenza A viruses
    Masatoshi Okamatsu; Fei Feng; Tatsuya Ohyanagi; Noriko Nagahori; Kazuhiko Someya; Yoshihiro Sakoda; Nobuaki Miura; Shin-Ichiro Nishimura; Hiroshi Kida
    JOURNAL OF VIROLOGICAL METHODS, 187, 2, 390, 394, 2013年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Novel thiosialosides tethered to metal nanoparticles as potent influenza A virus haemagglutinin blockers
    Fei Feng; Yoshihiro Sakoda; Tatsuya Ohyanagi; Noriko Nagahori; Hitomi Shibuya; Masatoshi Okamastu; Nobuaki Miura; Hiroshi Kida; Shin-Ichiro Nishimura
    Antiviral Chemistry and Chemotherapy, 23, 2, 59, 65, 2013年, [査読有り]
    英語, 研究論文(学術雑誌)
  • The nucleoprotein is responsible for intracerebral pathogenicity of A/duck/Mongolia/47/2001 (H7N1) in chicks
    Norikazu Isoda; Yoshimi Tsuda; Shingo Asakura; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida
    ARCHIVES OF VIROLOGY, 157, 12, 2257, 2264, 2012年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Selection of Classical Swine Fever Virus with Enhanced Pathogenicity Reveals Synergistic Virulence Determinants in E2 and NS4B
    Tomokazu Tamura; Yoshihiro Sakoda; Fumi Yoshino; Takushi Nomura; Naoki Yamamoto; Yuka Sato; Masatoshi Okamatsu; Nicolas Ruggli; Hiroshi Kida
    JOURNAL OF VIROLOGY, 86, 16, 8602, 8613, 2012年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Development and evaluation of indirect enzyme-linked immunosorbent assay for a screening test to detect antibodies against classical swine fever virus
    Yoshihiro Sakoda; Hiroaki Wakamoto; Tehpin Tamura; Takushi Nomura; Michiko Naito; Hiroshi Aoki; Hiroshi Morita; Hiroshi Kida; Akio Fukusho
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 60, 2-3, 85, 94, 2012年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Recovery of Leptospires from Miniature Pigs Experimentally Infected with Leptospira interrogans Serovar Manilae Strain UP-MMC under Immunosuppressive Conditions by Dexamethasone
    Yoshihiro Sakoda; Michiko Naito; Mutsumi Ito; Yuki Ito; Norikazu Isoda; Tomohisa Tanaka; Takashi Umemura; Hiroshi Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 74, 7, 955, 958, 2012年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Purification of human and avian influenza viruses using cellulose sulfate ester (Cellufine Sulfate) in the process of vaccine production
    Yoshihiro Sakoda; Masatoshi Okamatsu; Norikazu Isoda; Naoki Yamamoto; Koichi Ozaki; Yasuto Umeda; Shigeyuki Aoyama; Hiroshi Kida
    MICROBIOLOGY AND IMMUNOLOGY, 56, 7, 490, 495, 2012年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Memory Immune Responses against Pandemic (H1N1) 2009 Influenza Virus Induced by a Whole Particle Vaccine in Cynomolgus Monkeys Carrying Mafa-A1*052:02
    Masahiko Arikata; Yasushi Itoh; Masatoshi Okamatsu; Toshinaga Maeda; Takashi Shiina; Keiko Tanaka; Shingo Suzuki; Misako Nakayama; Yoshihiro Sakoda; Hirohito Ishigaki; Ayato Takada; Hideaki Ishida; Kosuke Soda; Van Loi Pham; Hideaki Tsuchiya; Shinichiro Nakamura; Ryuzo Torii; Takeshi Shimizu; Hidetoshi Inoko; Iwao Ohkubo; Hiroshi Kida; Kazumasa Ogasawara
    PLOS ONE, 7, 5, e37220, 2012年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • An H9N2 Influenza Virus Vaccine Prepared from a Non-Pathogenic Isolate from a Migratory Duck Confers Protective Immunity in Mice against Challenge with an H9N2 Virus Isolated from a Girl in Hong Kong
    Naoki Nomura; Yoshihiro Sakoda; Kosuke Soda; Masatoshi Okamatsu; Hiroshi Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 74, 4, 441, 447, 2012年04月, [査読有り]
    英語, 研究論文(学術雑誌)
  • カモから分離されたH7インフルエンザウイルスのニワトリに対する病原性獲得メカニズム
    丸山 隼輝; 曽田 公輔; 岡松 正敏; 迫田 義博; 喜田 宏
    日本獣医学会学術集会講演要旨集, 153回, 229, 229, (公社)日本獣医学会, 2012年03月
    日本語
  • Reintroduction of H5N1 highly pathogenic avian influenza virus by migratory water birds, causing poultry outbreaks in the 2010-2011 winter season in Japan
    Yoshihiro Sakoda; Hiroshi Ito; Yuko Uchida; Masatoshi Okamatsu; Naoki Yamamoto; Kosuke Soda; Naoki Nomura; Saya Kuribayashi; Shintaro Shichinohe; Yuji Sunden; Takashi Umemura; Tatsufumi Usui; Hiroichi Ozaki; Tsuyoshi Yamaguchi; Toshiyuki Murase; Toshihiro Ito; Takehiko Saito; Ayato Takada; Hiroshi Kida
    JOURNAL OF GENERAL VIROLOGY, 93, 3, 541, 550, 2012年03月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Characterization of avian influenza viruses isolated from domestic ducks in Vietnam in 2009 and 2010
    Naoki Nomura; Yoshihiro Sakoda; Mayumi Endo; Hiromi Yoshida; Naoki Yamamoto; Masatoshi Okamatsu; Kenji Sakurai; Nam Van Hoang; Long Van Nguyen; Huy Duc Chu; Tien Ngoc Tien; Hiroshi Kida
    ARCHIVES OF VIROLOGY, 157, 2, 247, 257, 2012年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Highly pathogenic avian influenza virus H5N1 controls type I IFN induction in chicken macrophage HD-11 cells: a polygenic trait that involves NS1 and the polymerase complex
    Matthias Liniger; Herve R. Moulin; Yoshihiro Sakoda; Nicolas Ruggli; Artur Summerfield
    VIROLOGY JOURNAL, 9, 7, 2012年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • [Pestivirus].
    Sakoda Y
    Uirusu, 61, 239, 248, 2, 2011年12月, [査読有り]
  • Rapid typing of influenza viruses using super high-speed quantitative real-time PCR
    Akira Sakurai; Namiko Nomura; Reiko Nanba; Takayuki Sinkai; Tsunehito Iwaki; Taminori Obayashi; Kazuhiro Hashimoto; Michiya Hasegawa; Yoshihiro Sakoda; Akihiro Naito; Yoshihito Morizane; Mitsugu Hosaka; Kunio Tsuboi; Hiroshi Kida; Akemi Kai; Futoshi Shibasaki
    JOURNAL OF VIROLOGICAL METHODS, 178, 1-2, 75, 81, 2011年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Development of a highly sensitive immunochromatographic detection kit for H5 influenza virus hemagglutinin using silver amplification
    Atsuhiko Wada; Yoshihiro Sakoda; Takayoshi Oyamada; Hiroshi Kida
    JOURNAL OF VIROLOGICAL METHODS, 178, 1-2, 82, 86, 2011年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Antigenic and genetic analysis of H3N8 influenza viruses isolated from horses in Japan and Mongolia, and imported from Canada and Belgium during 2007-2010
    Masayuki Motoshima; Masatoshi Okamatsu; Shingo Asakura; Saya Kuribayashi; Sugar Sengee; Damdinjav Batchuluun; Mika Ito; Yukiko Maeda; Mariko Eto; Yoshihiro Sakoda; Ruuragchaa Sodnomdarjaa; Hiroshi Kida
    ARCHIVES OF VIROLOGY, 156, 8, 1379, 1385, 2011年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration
    Masahiro Kajihara; Keita Matsuno; Edgar Simulundu; Mieko Muramatsu; Osamu Noyori; Rashid Manzoor; Eri Nakayama; Manabu Igarashi; Daisuke Tomabechi; Reiko Yoshida; Masatoshi Okamatsu; Yoshihiro Sakoda; Kimihito Ito; Hiroshi Kida; Ayato Takada
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 59, 2-3, 89, 100, 2011年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Evaluation of the Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) as a Screening Method for the Detection of Influenza Viruses in the Fecal Materials of Water Birds
    Hiromi Yoshida; Yoshihiro Sakoda; Mayumi Endo; Masayuki Motoshima; Fumi Yoshino; Naoki Yamamoto; Masatoshi Okamatsu; Takahiro Soejima; Syouhei Senba; Hidetoshi Kanda; Hiroshi Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 73, 6, 753, 758, 2011年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • A Low Pathogenic H5N2 Influenza Virus Isolated in Taiwan Acquired High Pathogenicity by Consecutive Passages in Chickens
    Kosuke Soda; Ming-Chu Cheng; Hiromi Yoshida; Mayumi Endo; Shu-Hwae Lee; Masatoshi Okamatsu; Yoshihiro Sakoda; Ching-Ho Wang; Hiroshi Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 73, 6, 767, 772, 2011年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • H9N2 influenza virus vaccine prepared from a non-pathogenic isolate from a natural reservoir conferred protective immunity against the challenge with a human H9N2 virus in mice
    Naoki Nomura; Yoshihiro Sakoda; Kosuke Soda; Masatoshi Okamatsu; Hiroshi Kida
    INFLUENZA AND OTHER RESPIRATORY VIRUSES, 5, 363, 366, 2011年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • H9N2 influenza virus acquires intravenous pathogenicity on the introduction of a pair of di-basic amino acid residues at the cleavage site of the hemagglutinin and consecutive passages in chickens
    Kosuke Soda; Shingo Asakura; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida
    INFLUENZA AND OTHER RESPIRATORY VIRUSES, 5, 272, 276, 2011年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Development of a novel rapid immunochromatographic test specific for the H5 influenza virus
    Eiji Miyagawa; Hiroyuki Kogaki; Yoshiaki Uchida; Nobuyuki Fujii; Takashi Shirakawa; Yoshihrio Sakoda; Hiroshi Kida
    JOURNAL OF VIROLOGICAL METHODS, 173, 2, 213, 219, 2011年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Improvement of the H5N1 influenza virus vaccine strain to decrease the pathogenicity in chicken embryos
    Norikazu Isoda; Yoshihiro Sakoda; Masatoshi Okamatsu; Yoshimi Tsuda; Hiroshi Kida
    ARCHIVES OF VIROLOGY, 156, 4, 557, 563, 2011年04月, [査読有り]
    英語, 研究論文(学術雑誌)
  • H9N2 influenza virus acquires intravenous pathogenicity on the introduction of a pair of di-basic amino acid residues at the cleavage site of the hemagglutinin and consecutive passages in chickens
    Kosuke Soda; Shingo Asakura; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida
    VIROLOGY JOURNAL, 8, 64, 2011年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Characterization of a non-pathogenic H5N1 influenza virus isolated from a migratory duck flying from Siberia in Hokkaido, Japan, in October 2009
    Naoki Yamamoto; Yoshihiro Sakoda; Masayuki Motoshima; Fumi Yoshino; Kosuke Soda; Masatoshi Okamatsu; Hiroshi Kida
    VIROLOGY JOURNAL, 8, 65, 2011年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Virological surveillance and phylogenetic analysis of the PB2 genes of influenza viruses isolated from wild water birds flying from their nesting lakes in Siberia to Hokkaido, Japan in autumn
    Rozanah Asmah Abdul Samad; Yoshihiro Sakoda; Yoshimi Tsuda; Edgar Simulundu; Rashid Manzoor; Masatoshi Okamatsu; Kimihito Ito; Hiroshi Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 59, 1, 15, 22, 2011年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • A vaccine prepared from a non-pathogenic H5N1 influenza virus strain from the influenza virus library conferred protective immunity to chickens against the challenge with antigenically drifted highly pathogenic avian influenza virus
    Rozanah Asmah Abdul Samad; Naoki Nomura; Yoshimi Tsuda; Rashid Manzoor; Masahiro Kajihara; Daisuke Tomabechi; Takashi Sasaki; Norihide Kokumai; Toshiaki Ohgitani; Masatoshi Okamatsu; Ayato Takada; Yoshihiro Sakoda; Hiroshi Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 59, 1, 23, 29, 2011年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Reactivity and prevalence of neutralizing antibodies against Japanese strains of bovine viral diarrhea virus subgenotypes
    Fujiko Minami; Makoto Nagai; Mika Ito; Tatsuhiko Matsuda; Hikaru Takai; Yoshiko Jinkawa; Takeshi Shimano; Michiko Hayashi; Yoshihisa Seki; Yoshihiro Sakoda; Katsuaki Sugiura; Hiroomi Akashi
    COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES, 34, 1, 35, 39, 2011年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Detection of highly pathogenic avian influenza virus infection in vaccinated chicken flocks by monitoring antibodies against non-structural protein 1 (NS1)
    Natsumi Takeyama; Kenji Minari; Masahiro Kajihara; Norikazu Isoda; Ryuichi Sakamoto; Takashi Sasaki; Norihide Kokumai; Noriyasu Takikawa; Rikiya Shiraishi; Masaji Mase; Junko Hagiwara; Toshiaki Kodama; Takashi Imamura; Masashi Sakaguchi; Toshiaki Ohgitani; Akira Sawata; Masatoshi Okamatsu; Masatake Muramatsu; Kenji Tsukamoto; Zhifeng Lin; Kotaro Tuchiya; Yoshihiro Sakoda; Hiroshi Kida
    VETERINARY MICROBIOLOGY, 147, 3-4, 283, 291, 2011年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Genetic characterization and susceptibility on poultry and mammal of H7N6 subtype avian influenza virus isolated in Japan in 2009
    Yuko Uchida; Katsushi Kanehira; Masaji Mase; Nobuhiro Takemae; Chiaki Watanabe; Tatsufumi Usui; Yoshikazu Fujimoto; Toshihiro Ito; Manabu Igarashi; Kimihito Ito; Ayato Takada; Yoshihiro Sakoda; Masatoshi Okamatsu; Yu Yamamoto; Kikuyasu Nakamura; Hiroshi Kida; Yasuaki Hiromoto; Tomoyuki Tsuda; Takehiko Saito
    VETERINARY MICROBIOLOGY, 147, 1-2, 1, 10, 2011年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Antigenic, genetic, and pathogenic characterization of H5N1 highly pathogenic avian influenza viruses isolated from dead whooper swans (Cygnus cygnus) found in northern Japan in 2008
    Masatoshi Okamatsu; Tomohisa Tanaka; Naoki Yamamoto; Yoshihiro Sakoda; Takashi Sasaki; Yoshimi Tsuda; Norikazu Isoda; Norihide Kokumai; Ayato Takada; Takashi Umemura; Hiroshi Kida
    VIRUS GENES, 41, 3, 351, 357, 2010年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Characterization of H5N1 highly pathogenic avian influenza virus strains isolated from migratory waterfowl in Mongolia on the way back from the southern Asia to their northern territory
    Yoshihiro Sakoda; Sengee Sugar; Damdinjav Batchluun; Tseren-Ochir Erdene-Ochir; Masatoshi Okamatsu; Norikazu Isoda; Kosuke Soda; Hiroki Takakuwa; Yoshimi Tsuda; Naoki Yamamoto; Noriko Kishida; Keita Matsuno; Eri Nakayama; Masahiro Kajihara; Ayaka Yokoyama; Ayato Takada; Ruuragchaa Sodnomdarjaa; Hiroshi Kida
    VIROLOGY, 406, 1, 88, 94, 2010年10月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Non-Cytopathic Bovine Viral Diarrhea Virus Infection Inhibits Differentiation of Bovine Neural Stem/progenitor Cells into Astrocytes in Vitro
    Kazuya Matsuda; Shintaro Kobayashi; Ken-ichiro Kameyama; Michiko Sato; Masateru Koiwa; Yoshihiro Sakoda; Hiroyuki Taniyama
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 72, 7, 903, 907, 2010年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • A Comparison of the Antibody Responses between Specific Pathogen-Free and Commercial Layers Immunized with an Influenza Vaccine Prepared from Inactivated Non-Pathogenic H5N1 Virus by Single Shot
    Takashi Sasaki; Norihide Kokumai; Toshiaki Ohgitani; Takashi Imamura; Akira Sawata; Zhifeng Lin; Yoshihiro Sakoda; Hiroshi Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 72, 6, 819, 821, 2010年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Novel trivalent anti-influenza reagent
    Fei Feng; Nobuaki Miura; Norikazu Isoda; Yoshihiro Sakoda; Masatoshi Okamatsu; Hiroshi Kida; Shin-Ichiro Nishimura
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 20, 12, 3772, 3776, 2010年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Isolation and Characterization of Potentially Pathogenic H5N2 Influenza Virus from a Chicken in Taiwan in 2008
    Ming-Chu Cheng; Kosuke Soda; Ming-Shiuh Lee; Shu-Hwae Lee; Yoshihiro Sakoda; Hiroshi Kida; Ching-Ho Wang
    AVIAN DISEASES, 54, 2, 885, 893, 2010年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Lipopolysaccharide treatment and inoculation of influenza A virus results in influenza virus-associated encephalopathy-like changes in neonatal mice
    Tomohisa Tanaka; Yuji Sunden; Yoshihiro Sakoda; Hiroshi Kida; Kenji Ochiai; Takashi Umemura
    JOURNAL OF NEUROVIROLOGY, 16, 2, 125, 132, 2010年04月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Amelioration of pneumonia with Streptococcus pneumoniae infection by inoculation with a vaccine against highly pathogenic avian influenza virus in a non-human primate mixed infection model
    Taichiro Miyake; Kosuke Soda; Yasushi Itoh; Yoshihiro Sakoda; Hirohito Ishigaki; Tomoya Nagata; Hideaki Ishida; Misako Nakayama; Hiroichi Ozaki; Hideaki Tsuchiya; Ryuzo Torii; Hiroshi Kida; Kazumasa Ogasawara
    JOURNAL OF MEDICAL PRIMATOLOGY, 39, 1, 58, 70, 2010年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Subcutaneous inoculation of a whole virus particle vaccine prepared from a non-pathogenic virus library induces protective immunity against H7N7 highly pathogenic avian influenza virus in cynomolgus macaques
    Yasushi Itoh; Hiroichi Ozaki; Hirohito Ishigaki; Yoshihiro Sakoda; Tomoya Nagata; Kosuke Soda; Norikazu Isoda; Taichiro Miyake; Hideaki Ishida; Kiyoko Okamoto; Misako Nakayama; Hideaki Tsuchiya; Ryuzo Torii; Hiroshi Kida; Kazumasa Ogasawara
    VACCINE, 28, 3, 780, 789, 2010年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Intranasal administration of a live non-pathogenic avian H5N1 influenza virus from a virus library confers protective immunity against H5N1 highly pathogenic avian influenza virus infection in mice: Comparison of formulations and administration routes of vaccines
    Yoshitaka Kashima; Mizuho Ikeda; Yasushi Itoh; Yoshihiro Sakoda; Tomoya Nagata; Taichiro Miyake; Kosuke Soda; Hiroichi Ozaki; Misako Nakayama; Hitomi Shibuya; Masatoshi Okamatsu; Hirohito Ishigaki; Hideaki Ishida; Toshihiro Sawai; Yoshihiro Kawaoka; Hiroshi Kida; Kazumasa Ogasawar
    VACCINE, 27, 52, 7402, 7408, 2009年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Hemagglutinin-Dependent Tropism of H5N1 Avian Influenza Virus for Human Endothelial Cells
    Manuela Ocana-Macchi; Michael Bel; Laurence Guzylack-Piriou; Nicolas Ruggli; Matthias Liniger; Kenneth C. McCullough; Yoshihiro Sakoda; Norikazu Isoda; Mikhail Matrosovich; Artur Summerfield
    JOURNAL OF VIROLOGY, 83, 24, 12947, 12955, 2009年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Effective Prevention against Rabies by Intracerebral Immunization in Mice
    Jae-Ho Shin; Yoshihiro Sakoda; Shiori Yano; Kenji Ochiai; Hiroshi Kida; Takashi Umemura
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 71, 10, 1331, 1336, 2009年10月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Long lasting immunity in chickens induced by a single shot of influenza vaccine prepared from inactivated non-pathogenic H5N1 virus particles against challenge with a highly pathogenic avian influenza virus
    Takashi Sasaki; Norihide Kokumai; Toshiaki Ohgitani; Ryuichi Sakamoto; Noriyasu Takikawa; Zhifeng Lin; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida
    VACCINE, 27, 38, 5174, 5177, 2009年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses
    Yasushi Itoh; Kyoko Shinya; Maki Kiso; Tokiko Watanabe; Yoshihiro Sakoda; Masato Hatta; Yukiko Muramoto; Daisuke Tamura; Yuko Sakai-Tagawa; Takeshi Noda; Saori Sakabe; Masaki Imai; Yasuko Hatta; Shinji Watanabe; Chengjun Li; Shinya Yamada; Ken Fujii; Shin Murakami; Hirotaka Imai; Satoshi Kakugawa; Mutsumi Ito; Ryo Takano; Kiyoko Iwatsuki-Horimoto; Masayuki Shimojima; Taisuke Horimoto; Hideo Goto; Kei Takahashi; Akiko Makino; Hirohito Ishigaki; Misako Nakayama; Masatoshi Okamatsu; Kazuo Takahashi; David Warshauer; Peter A. Shult; Reiko Saito; Hiroshi Suzuki; Yousuke Furuta; Makoto Yamashita; Keiko Mitamura; Kunio Nakano; Morio Nakamura; Rebecca Brockman-Schneider; Hiroshi Mitamura; Masahiko Yamazaki; Norio Sugaya; M. Suresh; Makoto Ozawa; Gabriele Neumann; James Gern; Hiroshi Kida; Kazumasa Ogasawara; Yoshihiro Kawaoka
    NATURE, 460, 7258, 1021, U110, 2009年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Generation of congenic mouse strains by introducing the virus-resistant genes, Mx1 and Oas1b, of feral mouse-derived inbred strain MSM/Ms into the common strain C57BL/6J
    Kanako Moritoh; Hideto Yamauchi; Atsushi Asano; Kentaro Yoshii; Hiroaki Kariwa; Ikuo Takashima; Norikazu Isoda; Yoshihiro Sakoda; Hiroshi Kida; Nobuya Sasaki; Takashi Agui
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 57, 2, 89, 99, 2009年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Propagation of Swine Hemagglutinating Encephalomyelitis Virus and Pseudorabies Virus in Dorsal Root Ganglia Cells
    Yoko Hara; Rie Hasebe; Yuji Sunden; Kenji Ochia; Eiichi Honda; Yoshihiro Sakoda; Takashi Umemura
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 71, 5, 595, 601, 2009年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Factors responsible for plaque formation of A/duck/Siberia/272/1998 (H13N6) influenza virus on MDCK cells
    Yoshimi Tsuda; Norikazu Isoda; Yoshihiro Sakoda; Hiroshi Kida
    VIRUS RESEARCH, 140, 1-2, 194, 198, 2009年03月, [査読有り]
    英語, 研究論文(学術雑誌)
  • PB2 Protein of a Highly Pathogenic Avian Influenza Virus Strain A/chicken/Yamaguchi/7/2004 (H5N1) Determines Its Replication Potential in Pigs
    Rashid Manzoor; Yoshihiro Sakoda; Naoki Nomura; Yoshimi Tsuda; Hiroichi Ozaki; Masatoshi Okamatsu; Hiroshi Kida
    JOURNAL OF VIROLOGY, 83, 4, 1572, 1578, 2009年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Evaluation of the potency, optimal antigen level and lasting immunity of inactivated avian influenza vaccine prepared from H5N1 virus
    Takashi Sasaki; Norikazu Isoda; Kosuke Soda; Ryuichi Sakamoto; Kazue Saijo; Junko Hagiwara; Norihide Kokumai; Toshiaki Ohgitani; Takashi Imamura; Akira Sawata; Zhifeng Lin; Yoshihiro Sakoda; Hiroshi Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 56, 4, 189, 198, 2009年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Classical Swine Fever Virus Can Remain Virulent after Specific Elimination of the Interferon Regulatory Factor 3-Degrading Function of N-pro
    Nicolas Ruggli; Artur Summerfield; Ana R. Fiebach; Laurence Guzylack-Piriou; Oliver Bauhofer; Catherine G. Lamm; Sandro Waltersperger; Keita Matsuno; Luzia Liu; Markus Gerber; Kyung H. Choi; Martin A. Hofmann; Yoshihiro Sakoda; Jon-Duri Tratschin
    JOURNAL OF VIROLOGY, 83, 2, 817, 829, 2009年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Antigenic structure of the hemagglutinin of H9N2 influenza viruses
    Masatoshi Okamatsu; Yoshihiro Sakoda; Noriko Kishida; Norikazu Isoda; Hiroshi Kida
    ARCHIVES OF VIROLOGY, 153, 12, 2189, 2195, 2008年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Antigenic and genetic analysis of H5 influenza viruses isolated from water birds for the purpose of vaccine use
    Kosuke Soda; Hiroichi Ozaki; Yoshihiro Sakoda; Norikazu Isoda; Yoshinari Haraguchi; Saori Sakabe; Noritaka Kuboki; Noriko Kishida; Ayato Takada; Hiroshi Kida
    ARCHIVES OF VIROLOGY, 153, 11, 2041, 2048, 2008年11月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Phylogenic analysis of the M genes of influenza viruses isolated from free-flying water birds from their Northern Territory to Hokkaido, Japan
    Rashid Manzoor; Yoshihiro Sakoda; Aaron Mweene; Yoshimi Tsuda; Noriko Kishida; Gui-Rong Bai; Ken-Ichiro Kameyama; Norikazu Isoda; Kosuke Soda; Michiko Naito; Hiroshi Kida
    VIRUS GENES, 37, 2, 144, 152, 2008年10月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Phylogenic analysis of the M genes of influenza viruses isolated from free-flying water birds from their Northern Territory to Hokkaido, Japan (Virus Genes DOI: 10.1007/s11262-008-0248-7)
    Rashid Manzoor; Yoshihiro Sakoda; Aaron Mweene; Yoshimi Tsuda; Noriko Kishida; Gui-Rong Bai; Ken-Ichiro Kameyama; Norikazu Isoda; Kosuke Soda; Michiko Naito; Hiroshi Kida
    Virus Genes, 37, 2, 153, 2008年10月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Potency of an inactivated avian influenza vaccine prepared from a non-pathogenic H5N1 reassortant virus generated between isolates from migratory ducks in Asia
    Norikazu Isoda; Yoshihiro Sakoda; Noriko Kishida; Kosuke Soda; Saori Sakabe; Ryuichi Sakamoto; Takashi Imamura; Masashi Sakaguchi; Takashi Sasaki; Norihide Kokumai; Toshiaki Ohgitani; Kazue Saijo; Akira Sawata; Junko Hagiwara; Zhifeng Lin; Hiroshi Kida
    ARCHIVES OF VIROLOGY, 153, 9, 1685, 1692, 2008年09月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Genetic Analyses of an H3N8 Influenza Virus Isolate, Causative Strain of the Outbreak of Equine Influenza at the Kanazawa Racecourse in Japan in 2007
    Mika Ito; Makoto Nagai; Yuji Hayakawa; Hirofumi Komae; Naruto Murakami; Syouichi Yotsuya; Shingo Asakura; Yoshihiro Sakoda; Hiroshi Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 70, 9, 899, 906, 2008年09月, [査読有り]
    英語, 研究論文(学術雑誌)
  • NS1-DIVAシステムを用いた国内製造鳥インフルエンザワクチン注射鶏のモニタリング
    竹山 夏実; 三成 健二; 坂元 隆一; 佐々木 崇; 瀧川 義康; 真瀬 昌司; 土屋 耕太郎; 岡松 正敏; 塚本 健司; 林 志鋒; 迫田 義博; 喜田 宏
    日本獣医学会学術集会講演要旨集, 146回, 193, 193, (公社)日本獣医学会, 2008年09月
    日本語
  • H2N5 influenza virus isolates from terns in Australia: genetic reassortants between those of the Eurasian and American lineages
    Noriko Kishida; Yoshihiro Sakoda; Mai Shiromoto; Gui-Rong Bai; Norikazu Isoda; Ayato Takada; Graeme Laver; Hiroshi Kida
    VIRUS GENES, 37, 1, 16, 21, 2008年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Development of a pen-site test kit for the rapid diagnosis of H7 highly pathogenic avian influenza
    Rashid Manzoor; Yoshihiro Sakoda; Saori Sakabe; Tsuyoshi Mochizuki; Yasuharu Namba; Yoshimi Tsuda; Hiroshi Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 70, 6, 557, 562, 2008年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Chemical deicer poisoning was suspected as a cause of the 2005-2006 wintertime mortality of small wild birds in Hokkaido
    Tomohisa Tanaka; Ginpei Tanoue; Masahiro Yamasaki; Ikuo Takashima; Yoshihiro Sakoda; Kenji Ochiai; Takashi Umemura
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 70, 6, 607, 610, 2008年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Cleavage of the NS2-3 protein in the cells of cattle persistently infected with non-cytopathogenic bovine viral diarrhea virus
    Ken-ichiro Kameyama; Yoshihiro Sakoda; Keita Matsuno; Asako Ito; Motoshi Tajima; Shigeyuki Nakamura; Hiroshi Kida
    MICROBIOLOGY AND IMMUNOLOGY, 52, 5, 277, 282, 2008年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • A vaccine prepared from a non-pathogenic H7N7 virus isolated from natural reservoir conferred protective immunity against the challenge with lethal dose of highly pathogenic avian influenza virus in chickens
    Saori Sakabe; Yoshihiro Sakoda; Yoshinari Haraguchi; Norikazu Isoda; Kosuke Soda; Hiroki Takakuwa; Kazue Saijo; Akira Sawata; Katsumi Kume; Junko Hagiwara; Kotaro Tuchiya; Zhifeng Lin; Ryuichi Sakamoto; Takashi Imamura; Takashi Sasaki; Norihide Kokumai; Yoshihiro Kawaoka; Hiroshi Kida
    VACCINE, 26, 17, 2127, 2134, 2008年04月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Identification of new genetic subtypes of bovine viral diarrhea virus genotype 1 isolated in Japan
    Makoto Nagai; Michiko Hayashi; Mika Itou; Toyoko Fukutomi; Hiroomi Akashi; Hiroshi Kida; Yoshihiro Sakoda
    VIRUS GENES, 36, 1, 135, 139, 2008年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • A vaccine prepared from a non-pathogenic H5N1 avian influenza virus strain confers protective immunity against highly pathogenic avian influenza virus infection in cynomolgus macaques
    Yasushi Itoh; Hiroichi Ozaki; Hideaki Tsuchiya; Kiyoko Okamoto; Ryuzo Torii; Yoshihiro Sakoda; Yoshihiro Kawaoka; Kazumasa Ogasawara; Hiroshi Kida
    VACCINE, 26, 4, 562, 572, 2008年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Development of vaccine strains of H5 and H7 influenza viruses
    Kosuke Soda; Yoshihiro Sakoda; Norikazu Isoda; Masahiro Kajihara; Yoshinari Haraguchi; Hitomi Shibuya; Hiromi Yoshida; Takashi Sasaki; Ryuichi Sakamoto; Kazue Saijo; Junko Hagiwara; Hiroshi Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 55, 2-3, 93, 98, 2008年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Carboxyl terminus of the 34 kDa protein of Mycobacterium paratuberculosis shares homologous B-cell epitopes with Mycobacterium avium and Mycobacterium intracellulare
    M. Malamo; K. Okazaki; Y. Sakoda; H. Kida
    VETERINARY RECORD, 161, 25, 853, 857, 2007年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Comparison of antibody titers in rabbits following immunization with inactivated influenza virus via subarachnoidal or subcutaneous route
    Jae-Ho Shin; Yoshihiro Sakoda; Jae Hoon Kim; Kenji Ochiai; Takashi Umemura
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 69, 11, 1167, 1169, 2007年11月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Genetic and pathobiological characterization of bovine viral diarrhea viruses recently isolated from cattle in Japan
    Keita Matsuno; Yoshihiro Sakoda; Ken-ichiro Kameyama; Kyuzo Tamai; Asako Ito; Hiroshi Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 69, 5, 515, 520, 2007年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Classical swine fever virus N-pro interacts with interferon regulatory factor 3 and induces its proteasomal degradation
    Oliver Bauhofer; Artur Summerfield; Yoshihiro Sakoda; Jon-Duri Tratschin; Martin A. Hofmann; Nicolas Ruggli
    JOURNAL OF VIROLOGY, 81, 7, 3087, 3096, 2007年04月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Serological evidence of influenza A virus infection in Kuril harbor seals (Phoca vitulina stejnegeri) of Hokkaido, Japan
    Kei Fujii; Chiharu Kakumoto; Mari Kobayashi; Sachiko Saito; Tatsuya Kariya; Yukiko Watanabe; Yoshihiro Sakoda; Hiroshi Kida; Masatsugu Suzuki
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 69, 3, 259, 263, 2007年03月, [査読有り]
    英語, 研究論文(学術雑誌)
  • H5N2鳥インフルエンザウイルスを接種したSFP鶏における抗体応答の長期観察と野外感染例の解析
    岡松 正敏; 加茂前 仁弥; 棚橋 美和; 迫田 義博; 真瀬 昌司; 塚本 健司; 喜田 宏; 山口 成夫
    日本獣医学会学術集会講演要旨集, 143回, 195, 195, (公社)日本獣医学会, 2007年03月
    日本語
  • Scrub typhus serologic testing with the indirect immunofluorescence method as a diagnostic gold standard: A lack of consensus leads to a lot of confusion
    Stuart D. Blacksell; Naomi J. Bryant; Daniel H. Paris; Jenny A. Doust; Yoshihiro Sakoda; Nicholas P. J. Day
    CLINICAL INFECTIOUS DISEASES, 44, 3, 391, 401, 2007年02月, [査読有り]
    英語
  • Serological evidence of leptospiral infection in pig populations in different districts in Japan
    Michiko Naito; Yoshihiro Sakoda; Takayuki Kamikawa; Yoshiki Nitta; Kazuhiko Hirose; Mitsuaki Sakashita; Satoru Kurokawa; Hiroshi Kida
    MICROBIOLOGY AND IMMUNOLOGY, 51, 6, 593, 599, 2007年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Development of an immunochromatographic kit for rapid diagnosis of h5 avian influenza virus infection
    Yoshimi Tsuda; Yoshihiro Sakoda; Saori Sakabe; Tsuyoshi Mochizuki; Yasuharu Namba; Hiroshi Kida
    MICROBIOLOGY AND IMMUNOLOGY, 51, 9, 903, 907, 2007年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Development of an immunochromatographic test kit for rapid detection of bovine viral diarrhea virus antigen
    K. Kameyama; Y. Sakoda; K. Tamai; H. Igarashi; M. Tajima; T. Mochizuki; Y. Namba; H. Kida
    JOURNAL OF VIROLOGICAL METHODS, 138, 1-2, 140, 146, 2006年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Development of ELISA to detect antibodies specific to Mycobacterium avium subsp paratuberculosis with truncated 34 kDa proteins
    Mumeka Malamo; Yoshihiro Sakoda; Hiroichi Ozaki; Hiroshi Kida
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 54, 2-3, 99, 107, 2006年11月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Seroepidemiological survey of morbillivirus infection in Kuril harbor seals (Phoca vitulina stejnegeri) of Hokkaido, Japan
    Kei Fujii; Hiroki Sato; Chiharu Kakumoto; Mari Kobayashi; Sachiko Saito; Tatsuya Kariya; Yukiko Watanabe; Yoshihiro Sakoda; Chieko Kai; Hiroshi Kida; Masatsugu Suzuki
    JAPANESE JOURNAL OF VETERINARY RESEARCH, 54, 2-3, 109, 117, 2006年11月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Pathogenicity of a highly pathogenic avian influenza virus, A/chicken/Yamaguchi/7/04 (H5N1) in different species of birds and mammals
    N Isoda; Y Sakoda; N Kishida; GR Bai; K Matsuda; T Umemura; H Kida
    ARCHIVES OF VIROLOGY, 151, 7, 1267, 1279, 2006年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Genetic recombination at different points in the N-pro-coding region of bovine viral diarrhea viruses and the potentials to change their antigenicities and pathogenicities
    K Kameyama; Y Sakoda; K Tamai; M Nagai; H Akashi; H Kida
    VIRUS RESEARCH, 116, 1-2, 78, 84, 2006年03月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Improvement of a rapid diagnosis kit to detect either influenza a or B virus infections
    GR Bai; Y Sakoda; AS Mweene; N Fujii; H Minakawa; H Kida
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 68, 1, 35, 40, 2006年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Efficacy of intracerebral immunization against pseudorabies virus in mice
    Jae-Ho Shin; Yoshihiro Sakoda; Jae Hoon Kim; Tomohisa Tanaka; Hiroshi Kida; Takashi Kimura; Kenji Ochiai; Takashi Umemura
    MICROBIOLOGY AND IMMUNOLOGY, 50, 10, 823, 830, 2006年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Library of influenza virus strains for vaccine and diagnostic use against highly pathogenic avian influenza and human pandemics
    H Kida; Y Sakoda
    OIE/FAO International Scientific Conference on Avian Influenza, 124, 69, 72, 2006年, [査読有り]
    英語, 研究論文(国際会議プロシーディングス)
  • Efficacy of intracerebral immunization against pseudorabies virus in mice
    Jae-Ho Shin; Yoshihiro Sakoda; Hoon Kim Jae; Tomohisa Tanaka; Hiroshi Kida; Takashi Kimura; Kenji Ochiai; Takashi Umemura
    Microbiology and Immunology, 50, 10, 823, 830, Center for Academic Publications Japan, 2006年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Application of carbon nanotubes for detecting anti-hemagglutinins based on antigen-antibody interaction
    S Takeda; A Sbagyo; Y Sakoda; A Ishii; M Sawamura; K Sueoka; H Kida; K Mukasa; K Matsumoto
    BIOSENSORS & BIOELECTRONICS, 21, 1, 201, 205, 2005年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Pathogenicity of H5 influenza viruses for ducks
    N Kishida; Y Sakoda; N Isoda; K Matsuda; M Eto; Y Sunaga; T Umemura; H Kida
    ARCHIVES OF VIROLOGY, 150, 7, 1383, 1392, 2005年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Serological surveillance of canine leptospirosis in Mongolia
    N Odontsetseg; Y Sakoda; H Kida
    VETERINARY RECORD, 157, 4, 120, 121, 2005年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • In vitro demonstration of neural transmission of avian influenza A virus
    K Matsuda; T Shibata; Y Sakoda; H Kida; T Kimura; K Ochiai; T Umemura
    JOURNAL OF GENERAL VIROLOGY, 86, 4, 1131, 1139, 2005年04月, [査読有り]
    英語, 研究論文(学術雑誌)
  • The vagus nerve is one route of transneural invasion for intranasally inoculated influenza A virus in mice
    Matsuda K; Shibata T; Sakoda Y; Kida H; Kimura T; Ochiai K; Umemura T
    Journal of General Virology, 86, 1131, 1139, 2005年04月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Erratum: Serological evidence of the persistence of infection with Leptospira interrogans serovar hardjo in cattle in Mongolia (Microbiology and Immunology (2005) 49:9 (865-869))
    Namsraijav Odontsetseg; Yoshihiro Sakoda; Hiroshi Kida
    Microbiology and Immunology, 49, 11, 1017, 1018, 2005年
    英語, 研究論文(学術雑誌)
  • Importance of arginine 20 of the swine vesicular disease virus 2A protease for activity and virulence
    T Inoue; S Alexandersen; AT Clark; C Murphy; M Quan; SM Reid; Y Sakoda; HL Johns; GJ Belsham
    JOURNAL OF VIROLOGY, 79, 1, 428, 440, 2005年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Serological evidence of the persistence of infection with Leptospira interrogans serovar Hardjo in cattle in Mongolia
    N Odontsetseg; Y Sakoda; H Kida
    MICROBIOLOGY AND IMMUNOLOGY, 49, 9, 865, 869, 2005年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Evaluation of the ESPLINE (R) INFLUENZA A&B-N kit for the diagnosis of avian and swine influenza
    GR Bai; Y Sakoda; AS Mweene; N Kishida; T Yamada; H Minakawa; H Kida
    MICROBIOLOGY AND IMMUNOLOGY, 49, 12, 1063, 1067, 2005年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Co-infection of Staphylococcus aureus or Haemophilus paragallinarum exacerbates H9N2 influenza A virus infection in chickens
    N Kishida; Y Sakoda; M Eto; Y Sunaga; H Kida
    ARCHIVES OF VIROLOGY, 149, 11, 2095, 2104, 2004年11月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Phylogenetic analysis of bovine viral diarrhea viruses using five different genetic regions
    M Nagai; M Hayashi; S Sugita; Y Sakoda; M Mori; T Murakami; T Ozawa; N Yamada; H Akashi
    VIRUS RESEARCH, 99, 2, 103, 113, 2004年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Cytopathogenicity of classical swine fever viruses that do not show the exaltation of newcastle disease virus is associated with accumulation of NS3 in serum-free cultured cell lines
    H Aoki; Y Sakoda; S Nakamura; S Suzuki; A Fukusho
    JOURNAL OF VETERINARY MEDICAL SCIENCE, 66, 2, 161, 167, 2004年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Preparation of a panel of avian influenza viruses of different subtypes for vaccine strains against future pandemics
    Y Sakoda; T Ito; K Okazaki; A Takada; Y Ito; K Tamai; M Okamatsu; KF Shortridge; RG Webster; H Kida
    OPTIONS FOR THE CONTROL OF INFLUENZA V, 1263, 674, 677, 2004年, [査読有り]
    英語, 研究論文(国際会議プロシーディングス)
  • H9N2 influenza viruses prevalent in poultry in China are phylogenetically distinct from A/quail/Hong Kong/G1/97 presumed to be the donor of the internal protein genes of the H5N1 Hong Kong/97 virus
    JH Liu; K Okazaki; H Ozaki; Y Sakoda; QM Wu; FY Chen; H Kida
    AVIAN PATHOLOGY, 32, 5, 551, 560, 2003年10月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Insertion of cellular sequence and RNA recombination in the structural protein coding region of cytopathogenic bovine viral diarrhoea virus
    M Nagai; Y Sakoda; M Mori; M Hayashi; H Kida; H Akashi
    JOURNAL OF GENERAL VIROLOGY, 84, 2, 447, 452, 2003年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • An attenuating mutation in the 2A protease of swine vesicular disease virus, a picornavirus, regulates cap- and internal ribosome entry site-dependent protein synthesis
    Y Sakoda; N Ross-Smith; T Inoue; GJ Belsham
    JOURNAL OF VIROLOGY, 75, 22, 10643, 10650, 2001年11月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Genomic and serological diversity of bovine viral diarrhea virus in Japan
    M Nagai; T Ito; S Sugita; A Genno; K Takeuchi; T Ozawa; Y Sakoda; T Nishimori; K Takamura; H Akashi
    ARCHIVES OF VIROLOGY, 146, 4, 685, 696, 2001年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Induction of antibodies in mice by a recombinant baculovirus expressing pseudorabies virus glycoprotein B in mammalian cells
    H Aoki; Y Sakoda; K Jukuroki; A Takada; H Kida; A Fukusho
    VETERINARY MICROBIOLOGY, 68, 3-4, 197, 207, 1999年08月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Genetic heterogeneity of porcine and ruminant pestiviruses mainly isolated in Japan
    Yoshihiro Sakoda; Shin-Ichi Ozawa; Sudarat Damrongwatanapokin; Mitsuo Sato; Kiyoyasu Ishikawa; Akio Fukusho
    Veterinary Microbiology, 65, 1, 75, 86, 1999年02月23日, [査読有り]
    英語, 研究論文(学術雑誌)
  • Establishment of a serum-free culture cell line, CPK-NS, which is useful for assays of classical swine fever virus
    Y Sakoda; M Hikawa; T Tamura; A Fukusho
    JOURNAL OF VIROLOGICAL METHODS, 75, 1, 59, 68, 1998年11月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Establishment and characterization of a porcine kidney cell line, FS-L3, which forms unique multicellular domes in serum-free culture
    Y Sakoda; A Fukusho
    IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, 34, 1, 53, 57, 1998年01月, [査読有り]
    英語, 研究論文(学術雑誌)
  • INHIBITION OF PSEUDORABIES VIRUS-REPLICATION BY A CHIMERIC TRANS-GENE PRODUCT REPRESSING TRANSCRIPTION OF THE IMMEDIATE-EARLY GENE
    E ONO; Y SAKODA; S TAHARAGUCHI; S WATANABE; N TONOMURA; H KIDA; Y SHIMIZU
    VIROLOGY, 210, 1, 128, 140, 1995年06月, [査読有り]
    英語, 研究論文(学術雑誌)
■ その他活動・業績
■ 主な担当授業
  • 研究・臨床セミナー, 2024年, 学士課程, 獣医学部
  • 越境性感染症学特論, 2024年, 博士後期課程, 国際感染症学院
  • 感染症学特別研究Ⅰ, 2024年, 博士後期課程, 国際感染症学院
  • 研究倫理演習, 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
  • 研究倫理演習, 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
  • 微生物学Ⅱ, 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
  • 微生物学Ⅰ, 2024年, 学士課程, 獣医学部
■ 所属学協会
  • 2021年04月 - 現在
    日本野生動物医学会
  • 日本家畜衛生学会
  • 日本ウイルス学会
  • 日本獣医学会
■ 共同研究・競争的資金等の研究課題
  • 野外株の抗原性解析に基づくペスチウイルス感染症の次世代型ワクチン株作出基盤の確立
    科学研究費助成事業
    2025年04月01日 - 2028年03月31日
    迫田 義博; 五十嵐 学; 青木 博史
    日本学術振興会, 基盤研究(B), 北海道大学, 25K02165
  • 豚熱ウイルスと非定型豚ペスチウイルスの持続感染に関与するErns蛋白質の機能解析
    科学研究費助成事業
    2022年04月01日 - 2025年03月31日
    迫田 義博; 五十嵐 学; 青木 博史
    豚熱(CSF)ウイルスおよび非定型豚ペスチ(APP)ウイルスの病原性、特に持続感染を引き起こす分子基盤を解明するために、2つのウイルスが属するフラビウイルス科ペスチウイルス属において病原性因子として細胞の内・外からその機能が発揮できるウイルス構造蛋白質Ernsに着目する。ウイルスがブタに持続感染し、結果として胎子や新生子豚に病原性を発揮するきっかけとなる宿主免疫からの回避と制御された細胞死の抑制に関するErns蛋白質の機能を調べる。
    まず、Erns蛋白質の三次元構造と自然免疫の抑制に重要なRNase活性およびⅠ型インターフェロンの産生調節の比較するために、近年国内で分離された中程度の病原性のCSFウイルス野外株、古典的な野外強毒株、およびワクチン株GPE-株のErns遺伝子を真核細胞発現プラスミドにクローニングした。同様に、APPウイルスのErns遺伝子を真核細胞発現プラスミドにクローニングした。これらのプラスミドから発現させた組換えErns蛋白質の自然免疫の抑制に関与するRNase活性とⅠ型インターフェロンの産生抑制能をウイルス株間で比較するための実験系を構築した。またAPPウイルスErns蛋白質の構造を解析し、CSFウイルスのそれと比較してRNase活性ドメインのモチーフに特有の配列があることがわかった。さらに、APPウイルス国内分離株をブタに接種し、臨床症状の観察に加え、ウイルスの生体での検出期間、各臓器における組織病変を確認した。その結果、豚での増殖は非常に限定的であることがわかった。
    日本学術振興会, 基盤研究(B), 北海道大学, 23K23769
  • 豚熱ウイルスと非定型豚ペスチウイルスの持続感染に関与するErns蛋白質の機能解析
    科学研究費助成事業
    2022年04月01日 - 2025年03月31日
    迫田 義博; 五十嵐 学; 青木 博史
    日本学術振興会, 基盤研究(B), 北海道大学, 22H02504
  • 口蹄疫、豚コレラウイルス由来IRES共通因子の探索と制御に向けた基礎的研究
    科学研究費助成事業 基盤研究(B)
    2020年04月01日 - 2023年03月31日
    小原 恭子; 岡林 環樹; 迫田 義博
    口蹄疫や豚熱は一度発生すると畜産業に甚大な被害を与える家畜伝染病で、制圧に多国間の協力を要する越境性動物疾病である。これらの原因ウイルスである口蹄疫ウイルス(FMDV)や豚熱ウイルス(CSFV)のゲノム5’端には、長い非翻訳領域(IRES)が存在し、リボゾームが認識してウイルス蛋白質合成を開始する。IRESを標的にして複製を抑制できる事が同属ウイルスで報告されており、IRES遺伝子配列が比較的保存している事からより広いスペクトラムの抗ウイルス作用の標的となる事が期待できる。これまでに、FMDV-IRESやCSFV-IRESを標的としたshRNA発現ベクターを開発し、IRES阻害効果を確認している。このうち、FMDV-IRESのshRNAは、FMDVの7血清型で保存した遺伝子領域を標的としている。また、FMDV-IRESに作用する宿主因子については、IRES活性を阻害するフランス松樹液のピクノジュノール(PYC)を作用した際に発現が変化するものをマイクロアレイで解析し、大きく発現抑制される宿主因子に対してsiRNAを設計してこれら因子の関与を確認した。同時にこれらの因子のうち、CSFV-IRESでも作用する因子をsiRNAで確認した。作用の強いものから、polycystic kidney disease 1-like 3 (PKD1L3)、ubiquitin-specific peptidase 31 (USP31)が同定されている(Ide et al., Sci. Rep., accepted 2022)。今後は、これらの因子の生体におけるIRES制御作用を解明するため、ノックアウトマウスの樹立を実施する予定である。
    日本学術振興会, 基盤研究(B), 鹿児島大学, 20H03164
  • 豚コレラウイルスの多様な病原性を規定するウイルス因子の機能解明
    科学研究費助成事業 基盤研究(B)
    2019年04月01日 - 2022年03月31日
    迫田 義博; 青木 博史
    豚コレラウイルスの多様な病原性の分子基盤を理解するためには、豚コレラウイルスの病原性に関与する新規ウイルス因子の同定と、既報のウイルス因子との相乗効果を評価する必要がある。さらに、準種(Major集団とMinor集団)に由来するウイルス蛋白の活性バランスが病原性発揮に寄与することを証明することが必要である。
    そこでまず、2019年に日本国内のイノシシから分離された豚コレラウイルスCSFV/wb/Jpn-Mie/P96/2019株をブタに実験的に感染させ、その病原性が中程度であることを確認した。またこのCSFV/wb/Jpn-Mie/P96/2019株の全遺伝子配列を決定した。さらにCSFV/wb/Jpn-Mie/P96/2019株、近年海外で分離された野外株、高病原性標準株および弱毒生ワクチン株のアミノ酸配列を比較し、新しい病原性因子と考えられるウイルス蛋白および遺伝子領域の特定を試みた。その結果、ウイルス構造蛋白Ernsの病原性関連ドメインであるRNase活性ドメインとは異なる領域にウイルスのアポトーシスを制御する機能があることを明らかにした。
    この結果を基に、豚コレラウイルスのErns蛋白のアミノ酸をアポトーシスを誘導するアミノ酸に置換した変異ウイルスをリバースジェネティクス法により作出した。この組換えウイルスをブタに接種したところ、ウイルスの体内増殖に影響を与えないものの、接種豚における病原性スコアの優位な上昇を確認した。以上より、Erns蛋白上の病原性に関与する新規ドメインを同定することができた。
    日本学術振興会, 基盤研究(B), 北海道大学, 19H03115
  • 分子生物学的研究・大規模臨床研究・統計解析の集約によるインフルエンザ治療の再評価
    科学研究費助成事業 基盤研究(C)
    2013年04月01日 - 2017年03月31日
    石黒 信久; 迫田 義博; 海方 美紀; 有賀 正; 大庭 幸治
    現在、4種類の抗ノイラミニダーゼ阻害薬(ラニナミビル、オセルタミビル、ペラミビル、ザナミビル)がインフルエンザの治療に用いられている。これらの効果的な使い分けを検討するために、本研究を行い、次の結論を得た。(1) インフルエンザA型に感染した0-18歳の小児患者にはオセルタミビル群とペラミビル群の効果が有意に高かった。(2) 同様に、インフルエンザB型に感染した0-18歳の小児患者にはラニナミビル群とザナミビル群の効果が有意に高かった。
    日本学術振興会, 基盤研究(C), 北海道大学, 25461577
  • ペスチウイルスの持続感染に関与する免疫回避機構の解明
    科学研究費助成事業 基盤研究(B)
    2013年04月01日 - 2014年03月31日
    迫田 義博
    日本学術振興会, 基盤研究(B), 北海道大学, 25292166
  • 豚コレラウイルスの病原性に関与する自然免疫回避機構の解明
    科学研究費補助金(基盤研究(B))
    2007年 - 2009年
    迫田 義博; 青木 博史
    豚コレラウイルスの病原性発揮に関与すると考えられている自然免疫回避機構を分子レベルで解明することを目的とし、ウイルス非構造蛋白N^の点変異体や欠損体を作製し、1型IFNの産生抑制に必須なアミノ酸領域を決定した。このアミノ酸の変異は、(1)C112R、(2)D136N、(3)H5Y、L8F、P17Sのいずれかであることがわかった。また、この自然免疫の調節に関与するN^上のアミノ酸の変異は、豚における病原性発揮の要因の1つであることを明らかにした。
    文部科学省, 基盤研究(B), 北海道大学, 研究代表者, 競争的資金, 19380170
  • 動物インフルエンザウイルスの生態解明と新型ウイルス対策
    科学研究費補助金(基盤研究(S))
    2003年 - 2006年
    喜田 宏; 岡崎 克則; 河岡 義裕; 迫田 義博; 梅村 孝司; 伊藤 壽啓; 小笠原 一誠
    本研究は、家禽と家畜のインフルエンザの被害を未然に防ぐとともに、ヒトの新型インフルエンザウイルスの出現に備え、その予防と制圧に資することを目的とする。・動物インフルエンザのグローバルサーベイランスによるウイルス分布の解明2006年秋、日本、モンゴルにおいて採取された渡りガモおよびハクチョウの糞便材料からのウイルス分離を試みた。1,201検体の材料から合計55株のインフルエンザAウイルスを分離同定した。これらの分離株にはH5やH7亜型のインフルエンザウイルスは含まれていなかった。これまでのウイルス分離の成績と合わせると、H1-H16およびN1-N9までの144通りの組合せのうち、133通りのウイルスの系統保存を完了した。・インフルエンザウイルスの病原性決定因子の同定2006年夏、モンゴルの湖沼で死亡野烏が再び発見され、死亡したオオハクチョウおよびホオジロガモの臓器材料からH5N1亜型の高病原性鳥インフルエンザウイルスが分離された。分離されたウイルスは、2005年中国やモンゴルの野生水禽から分離された高病原性のH5N1ウイルスと8つの遺伝子分節すべてが近縁であった。また、このウイルスに対して哺乳動物が高い感受性を示すことが動物試験から明らかにした。・ベッドサイド早期迅速インフルエンザ診断法の開発A型インフルエンザウイルスH5およびH7亜型抗原を特異的に検出する簡易診断キットを開発...
    文部科学省, 基盤研究(S), 北海道大学, 連携研究者, 競争的資金, 15108004
  • 牛ウイルス性下痢症ウイルス感染牛の呈する非典型的臨床症状と病原因子との関連性
    科学研究費補助金(基盤研究(B))
    2003年 - 2005年
    田島 誉士; 迫田 義博; 落合 謙爾
    自然発生の牛ウイルス性下痢症ウイルス(BVDV)持続感染牛(PI)の臨床症状と分離されたウイルスの遺伝子亜型との関係を調べた。1991〜2005年までの間に摘発された150検体について、BVDVの主要抗原であるE2をコードする遺伝子の塩基配列を解読し、遺伝子亜型を決定した。その結果、13検体が世界的にきわめて稀な1c亜型に分類された。これらの症例には、運動障害を主徴とする中枢神経異常の症状が高率に認められ、病理解剖によって大脳に肉眼病変が認められた症例もあった。また、糖尿病併発BVDV感染牛から検出されたBVDVはすべて1a亜型に分類され、それぞれが遺伝学的に非常に近縁であり、小クラスターを形成していた。以上のことから、BVDV感染に併発する中枢神経異常および糖尿病は、特定の遺伝子亜型に属するBVDVと密接な関連性があることが示唆された。1c亜型に属するBVDVとその病態との関連性を組織学的に検索したところ、1c亜型特異的な脳内局在は確認できなかったが、1cは他の亜型のBVDVよりも高率に大脳神経細胞内で確認された。定性PCRでは、BVDV遺伝子型に関係なく各臓器からウイルス遺伝子が検出されたが、定量PCRによって各臓器局在のウイルス量の違いは確認されなかった。また、PIで高率に認められる発育不良とBVDV感染との関係を検討した。外見上ほぼ正常なPIと著しい発育不良のPIとか...
    文部科学省, 基盤研究(B), 北海道大学, 連携研究者, 競争的資金, 15380212
  • 牛ウイルス性下痢ウイルスの病原性獲得に与る宿主遺伝子の役割に関する研究
    科学研究費補助金(若手研究(B))
    2003年 - 2004年
    迫田 義博
    牛ウイルス性下痢ウイルス(BVDV)に感染した牛が致死的な粘膜病を発病する際には、ウイルス遺伝子内に宿主由来遺伝子が挿入することが明らかになっている。この宿主遺伝子の一つとしてcINS遺伝子がある。このcINS遺伝子から翻訳される蛋白は分子シャペロンとして機能し、BVDVの病原性発揮に関与していると考えられるが、詳細は不明である。本年度は、昨年作出した組換えcINS蛋白に対するモノクローン抗体、およびNS2-3蛋白発現プラスミドを用いて、cINS蛋白がNS2-3蛋白の開裂に直接作用するのかを明らかにするとともに、分子シャペロンであるcINS蛋白と相互作用すると考えられる新たな宿主因子をTwo Hybridシステムで検索した。その結果、cINS蛋白とNS2-3は直接結合することがわかった。しかし、NS2-3の開裂には宿主由来の蛋白が2つ必須であることが明らかになった。現在これらの宿主因子の機能解析を詳細に行っている。また、作製されたモノクローン抗体を利用して、cINS遺伝子がウイルスゲノムに取り込まれているウイルス株を野外ウイルス株から選択し、Nose株の病原性獲得メカニズムとの比較を行った。その結果、野外にはNose株と同様の病原性獲得メカニズムによって病原性を獲得したと思われるウイルスが1株確認された。さらに、BVDVと同じペスチウイルスに属する豚コレラウイルスの新たな細胞...
    文部科学省, 若手研究(B), 北海道大学, 研究代表者, 競争的資金, 15780193
  • ウシウイルス性下痢症ウイルスの遺伝的多様性:貿易のための防疫対策確立
    科学研究費補助金(基盤研究(B))
    2001年 - 2003年
    田島 誉士; 山崎 真大; 大和 修; 迫田 義博
    過去十数年の間に欧米各国で分離された、牛ウイルス性下痢症ウイルス(BVDV)野外分離株の主要抗原であるE2をコードする領域を基に、遺伝子型を解析した。ドイツ北部で分離されたBVDVは、ほとんどが1bおよび1d亜型に分類された。検索した62BVDV中それぞれの占める割合は50.0および40.3%であった。1d亜型はドイツ国内に分布する独特の遺伝子型であると考えられた。北米での流行BVDVの遺伝子型を検討したところ、56例中26例(37.5%)がBVDV2であった。この比率は、日本および欧州における流行比率より非常に高く、BVDV2は北米特有の流行ウイルスである可能性が示唆された。これらのBVDV2はさらに大小二つの亜型(2aおよび2c)に分類することが可能であった。北米で分離されたBVDV1は、ほとんどが1b亜型に分類された。検索した32株中26株が1b亜型に分類された。古典的代表株の属する1a亜型に分類されたのは6株のみであった。さらに、今回確認された北米の1b亜型は、これまでに本研究で明らかにされてきた日本およびドイツで流行している1b亜型とは異なるクラスターを形成しており、この領域の遺伝子を解析することは、日独米の流行ウイルスを区別するための有用な手段になると考えられた。各国の流行パターンを遺伝子型で比較すると、日本は1aおよび1b、ドイツは1bおよび1d、北米は1bおよ...
    文部科学省, 基盤研究(B), 北海道大学, 連携研究者, 競争的資金, 13575028
  • 動物インフルエンザウイルスの生態学的研究:新型ウイルスの出現に備えて
    科学研究費補助金(基盤研究(A))
    2000年 - 2002年
    喜田 宏; 高田 礼人; 河岡 義裕; 岡崎 克則; 伊藤 壽啓; 迫田 義博
    新型ウイルスの亜型予測に資するため、鳥類および動物インフルエンザウイルスの疫学調査を実施した。ロシア、モンゴル、中国および北海道で、渡りカモの糞便3,987検体を採取し、亜型の異なるインフルエンザAウイルス212株を分離した。宮城県のブタからH1N2ウイルスを分離した。北海道大学を含む動物インフルエンザセンター5機関で25株のH9ウイルス株を交換し、解析を共同で開始した。渡りカモのウイルス遺伝子を比較解析したところ、日本で分離されたH9インフルエンザウイルスと1996年に韓国でニワトリに被害をもたらしたウイルスが近縁であった。1995~1999年に中国のニワトリから分離されたH9N2ウイルスの遺伝子解析の結果、渡りカモのウイルスと異なる亜群に分類され、ノイラミニダーゼに欠損が認められた。内部蛋白遺伝子は1997年の香港の強毒H5N1ウイルスに内部蛋白遺伝子を供給したH9N2ウイルスの系統とは異なった。香港のブタ、カスピ海のアザラシの抗体調査を行い、インフルエンザウイルスが感染した成績を得た。インフルエンザウイルスの異種動物間伝播機構を明らかにするため、ニワトリ雛の気嚢継代によって得たニワトリ馴化株の遺伝子再集合体を作出し、ニワトリ肺における増殖性を調べた。HA遺伝子を入れ替えた遺伝子再集合体の増殖性に変化はなく、他の因子が関与することが示唆された。新型ウイルスの出現に備え世界...
    文部科学省, 基盤研究(A), 北海道大学, 連携研究者, 競争的資金, 12375006
  • ウイルス病の予防に関する研究
    競争的資金
  • Study on prophylaxis of viral disease
    競争的資金
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