Current research and future directions for realizing the ideal One-Health approach: A summary of key-informant interviews in Japan and a literature review

The COVID-19 pandemic has highlighted the importance of the One Health (OH) approach, which considers the health of humans, animals, and the environment in preventing future pandemics. A wide range of sustainable interdisciplinary collaborations are required to truly fulfill the purpose of the OH approach. It is well-recognized, however, that such collaborations are challenging. In this study, we undertook key-informant interviews with a panel of stakeholders from Japan to identify their perceived needs and challenges related to OH research. This panel included scientists, government officials, journalists, and industry stakeholders. By combining a thematic analysis of these interviews and a literature review, we summarized two key themes pertinent to the effective implementation of OH research: types of required research and systems to support that research. As a technological issue, interviewees suggested the importance of research and development of methodologies that can promote the integration and collaboration of research fields that are currently fragmented. An example of such a methodology would allow researchers to obtain high-resolution metadata (e.g. ecological and wildlife data) with high throughput and then maximize the use of the obtained metadata in research, such as in environmental DNA analysis, database construction, or the use of computational algorithms to find novel viral genomes. In terms of systems surrounding OH research, some interviewees stressed the importance of creating a sustainable research system, such as one that has continuous budget support and allows researchers to pursue their academic careers and interests. These perceptions and challenges held by Japanese stakeholders may be common to others around the world. We hope this review will encourage more researchers and others to work together to create a resilient society against future pandemics

Pathogenicity of border disease virus FNK2012-1 strain isolated from a pig in the natural host, sheep

A first isolation of border disease virus (BDV) in Japan was from a pig on a farm without keeping any ruminants. Our previous study showed that this BDV, termed the FNK2012-1 strain, replicated inefficiently in swine-derived cells compared with those of ruminant origin. Pigs inoculated with this virus showed neither clinical symptoms nor viremia. In this study, we evaluated the pathogenicity of the FNK2012-1 strain in sheep, its natural host. The inoculated sheep showed clinical symptoms and transient viremia. Seroconversion was observed in the inoculated sheep. These results suggest that the FNK2012-1 strain was introduced from sheep and has not yet adapted to swine. Therefore, surveillance of border disease in Japan is necessary among both the swine and ruminant populations

Genetic Diversity of the Hemagglutinin Genes of Influenza a Virus in Asian Swine Populations

Swine influenza (SI) is a major respiratory disease of swine; SI is due to the influenza A virus of swine (IAV-S), a highly contagious virus with zoonotic potential. The intensity of IAV-S surveillance varies among countries because it is not a reportable disease and causes limited mortality in swine. Although Asia accounts for half of all pig production worldwide, SI is not well managed in those countries. Rigorously managing SI on pig farms could markedly reduce the economic losses, the likelihood of novel reassortants among IAV-S, and the zoonotic IAV-S infections in humans. Vaccination of pigs is a key control measure for SI, but its efficacy relies on the optimal antigenic matching of vaccine strains with the viral strains circulating in the field. Here, we phylogenetically reviewed the genetic diversity of the hemagglutinin gene among IAVs-S that have circulated in Asia during the last decade. This analysis revealed the existence of country-specific clades in both the H1 and H3 subtypes and cross-border transmission of IAVs-S. Our findings underscore the importance of choosing vaccine antigens for each geographic region according to both genetic and antigenic analyses of the circulating IAV-S to effectively manage SI in Asia

Genetic Diversity of the Hemagglutinin Genes of Influenza a Virus in Asian Swine Populations

Swine influenza (SI) is a major respiratory disease of swine; SI is due to the influenza A virus of swine (IAV-S), a highly contagious virus with zoonotic potential. The intensity of IAV-S surveillance varies among countries because it is not a reportable disease and causes limited mortality in swine. Although Asia accounts for half of all pig production worldwide, SI is not well managed in those countries. Rigorously managing SI on pig farms could markedly reduce the economic losses, the likelihood of novel reassortants among IAV-S, and the zoonotic IAV-S infections in humans. Vaccination of pigs is a key control measure for SI, but its efficacy relies on the optimal antigenic matching of vaccine strains with the viral strains circulating in the field. Here, we phylogenetically reviewed the genetic diversity of the hemagglutinin gene among IAVs-S that have circulated in Asia during the last decade. This analysis revealed the existence of country-specific clades in both the H1 and H3 subtypes and cross-border transmission of IAVs-S. Our findings underscore the importance of choosing vaccine antigens for each geographic region according to both genetic and antigenic analyses of the circulating IAV-S to effectively manage SI in Asia

Phylogeographic evidence for the inter- and intracontinental dissemination of avian influenza viruses via migration flyways.

Genetically related highly pathogenic avian influenza viruses (HPAIVs) of H5N6 subtype caused outbreaks simultaneously in East Asia and Europe-geographically distinct regions-during winter 2017-2018. This situation prompted us to consider whether the application of phylogeographic analysis to a particular gene segment of AIVs could provide clues for understanding how AIV had been disseminated across the continent. Here, the N6 NA genes of influenza viruses isolated across the world were subjected to phylogeographic analysis to illustrate the inter- and intracontinental dissemination of AIVs. Those isolated in East Asia during winter and in Mongolia/Siberia during summer were comingled within particular clades of the phylogeographic tree. For AIVs in one clade, their dissemination in eastern Eurasia extended from Yakutia, Russia, in the north to East Asia in the south. AIVs in western Asia, Europe, and Mongolia were also comingled within other clades, indicating that Mongolia/Siberia plays an important role in the dissemination of AIVs across the Eurasian continent. Mongolia/Siberia may therefore have played a role in the simultaneous outbreaks of H5N6 HPAIVs in Europe and East Asia during the winter of 2017-2018. In addition to the long-distance intracontinental disseminations described above, intercontinental disseminations of AIVs between Eurasia and Africa and between Eurasia and North America were also observed. Integrating these results and known migration flyways suggested that the migration of wild birds and the overlap of flyways, such as that observed in Mongolia/Siberia and along the Alaskan Peninsula, contributed to the long-distance intra- and intercontinental dissemination of AIVs. These findings highlight the importance of understanding the movement of migratory birds and the dynamics of AIVs in breeding areas-especially where several migration flyways overlap-in forecasting outbreaks caused by HPAIVs

The N-terminal domain of N-pro of classical swine fever virus determines its stability and regulates type I IFN production

The viral protein N-pro is unique to the genus Pestivirus within the family Flaviviridae. After autocatalytic cleavage from the nascent polyprotein, N-pro suppresses type I IFN (IFN-alpha/beta) induction by mediating proteasomal degradation of IFN regulatory factor 3 (IRF-3). Previous studies found that the N-pro-mediated IRF-3 degradation was dependent of a TRASH domain in the C-terminal half of N-pro coordinating zinc by means of the amino acid residues 0112, 0134, D136 and C138. Interestingly, four classical swine fever virus (CSFV) isolates obtained from diseased pigs in Thailand in 1993 and 1998 did not suppress IFN-alpha/beta induction despite the presence of an intact TRASH domain. Through systematic analyses, it was found that an amino acid mutation at position 40 or mutations at positions 17 and 61 in the N-terminal half of N-pro of these four isolates were related to the lack of IRF-3-degrading activity. restoring a histidine at position 40 or both a proline at position 17 and a lysine at position 61 based on the sequence of a functional N-pro contributed to higher stability of the reconstructed N-pro compared with the N-pro from the Thai isolate. This led to enhanced interaction of N-pro with IRF-3 along with its degradation by the proteasome. The results of the present study revealed that amino acid residues in the N-terminal domain of N-pro are involved in the stability of N-pro, in interaction of N-pro with IRF-3 and subsequent degradation of IRF-3, leading to downregulation of IFN-alpha/beta production

Different Infectivity and Transmissibility of H5N8 and H5N1 High Pathogenicity Avian Influenza Viruses Isolated from Chickens in Japan in the 2021/2022 Season

H5N8 and H5N1 high pathogenicity avian influenza viruses (HPAIVs) caused outbreaks in poultry farms in Japan from November 2021 to May 2022. Hemagglutinin genes of these viruses belong to clade 2.3.4.4B and can be divided phylogenetically into the following groups: 20A, 20E, and 21E. In this study, we compared the infectivity and transmissibility of HPAIVs from three groups of chickens. Representative strains from 20A, 20E, and 21E groups are A/chicken/Akita/7C/2021(H5N8)(Akita7C), A/chicken/Kagoshima/21A6T/2021(H5N1)(Kagoshima6T), and A/chicken/Iwate/21A7T/2022(H5N1)(Iwate7T), respectively. Fifty percent lethal dose of Akita7C in chickens (103.83 fifty percent egg infectious dose (EID50)) was up to seven times lower than those of Kagoshima6T and Iwate7T (104.50 and 104.68 EID50, respectively). Mean death times for Akita7C- and Kagoshima6T-infected chickens (3.45 and 3.30 days, respectively) were at least a day longer than that of Iwate7T (2.20 days). Viral titers of the trachea and cloaca of Iwate7T-infected chicken were the highest detected. The transmission rate of the Akita7C strain (100%) was markedly higher than those of the two strains (<50%). These data suggest that the infectivity and transmissibility of the Akita7C strain (H5N8) in chickens are higher than those of H5N1 viruses, providing fundamental information needed for formulating effective prevention and control strategies for HPAI outbreaks

Different Infectivity and Transmissibility of H5N8 and H5N1 High Pathogenicity Avian Influenza Viruses Isolated from Chickens in Japan in the 2021/2022 Season

H5N8 and H5N1 high pathogenicity avian influenza viruses (HPAIVs) caused outbreaks in poultry farms in Japan from November 2021 to May 2022. Hemagglutinin genes of these viruses belong to clade 2.3.4.4B and can be divided phylogenetically into the following groups: 20A, 20E, and 21E. In this study, we compared the infectivity and transmissibility of HPAIVs from three groups of chickens. Representative strains from 20A, 20E, and 21E groups are A/chicken/Akita/7C/2021(H5N8)(Akita7C), A/chicken/Kagoshima/21A6T/2021(H5N1)(Kagoshima6T), and A/chicken/Iwate/21A7T/2022(H5N1)(Iwate7T), respectively. Fifty percent lethal dose of Akita7C in chickens (103.83 fifty percent egg infectious dose (EID50)) was up to seven times lower than those of Kagoshima6T and Iwate7T (104.50 and 104.68 EID50, respectively). Mean death times for Akita7C- and Kagoshima6T-infected chickens (3.45 and 3.30 days, respectively) were at least a day longer than that of Iwate7T (2.20 days). Viral titers of the trachea and cloaca of Iwate7T-infected chicken were the highest detected. The transmission rate of the Akita7C strain (100%) was markedly higher than those of the two strains (&lt;50%). These data suggest that the infectivity and transmissibility of the Akita7C strain (H5N8) in chickens are higher than those of H5N1 viruses, providing fundamental information needed for formulating effective prevention and control strategies for HPAI outbreaks

Detection of H5N1 High Pathogenicity Avian Influenza Viruses in Four Raptors and Two Geese in Japan in the Fall of 2022

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