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Phylogenetic and molecular analyses were performed to characterize the genetic origin of the H3N8 strain. Phylogenetic analysis revealed that eight gene segments of this avian influenza virus H3N8 belong to Eurasian lineages. HA gene clustered with avian influenza viruses is circulating in poultry in southern China. The NA gene possibly originated from wild ducks in South Korea and has the highest homology (99.3%) with A\/Wild duck\/South Korea\/KNU2020-104\/2020 (H3N8), while other internal genes have a complex and wide range of origins. The HA cleavage site is PEKQTR\u2193GLF with one basic amino acid, Q226 and T228 at HA preferentially bind to the alpha-2,3-linked sialic acid receptor, non-deletion of the stalk region in the NA gene and no mutations at E627K and D701N of the PB2 protein, indicating that isolate A\/Chinese pond heron\/Jiangxi 5-1\/2021 (H3N8) was a typical avian influenza with low pathogenicity. However, there are some mutations that may increase pathogenicity and transmission in mammals, such as N30D, T215A of M1 protein, and P42S of NS1 protein. In animal studies, A\/Chinese pond heron\/Jiangxi 5-1\/2021 (H3N8) replicates inefficiently in the mouse lung and does not adapt well to the mammalian host. Overall, A\/Chinese pond heron\/Jiangxi 5-1\/2021 (H3N8) is a novel wild bird-origin H3N8 influenza virus reassortant from influenza viruses of poultry and wild birds. This wild bird-origin avian influenza virus is associated with wild birds along the East Asian-Australasian flyway. Therefore, surveillance of avian influenza viruses in wild birds should be strengthened to assess their mutation and pandemic risk in advance.<\/jats:p>","DOI":"10.3390\/v15020383","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T07:34:41Z","timestamp":1675064081000},"page":"383","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic Characterization and Pathogenesis of Avian Influenza Virus H3N8 Isolated from Chinese pond heron in China in 2021"],"prefix":"10.3390","volume":"15","author":[{"given":"Heng","family":"Zhang","sequence":"first","affiliation":[{"name":"Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Chuzhou 233100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Han","sequence":"additional","affiliation":[{"name":"National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2343-3680","authenticated-orcid":false,"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Xing","sequence":"additional","affiliation":[{"name":"National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohui","family":"Yuan","sequence":"additional","affiliation":[{"name":"National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Agriculture, Ningxia University, Yinchuan 750021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilei","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2433-0536","authenticated-orcid":false,"given":"Gaojian","family":"Li","sequence":"additional","affiliation":[{"name":"National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoqiao","family":"Li","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Chuzhou 233100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinchao","family":"Pan","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Chuzhou 233100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchao","family":"Li","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Chuzhou 233100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxuan","family":"He","sequence":"additional","affiliation":[{"name":"National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e03883","DOI":"10.7554\/eLife.03883","article-title":"Improving pandemic influenza risk assessment","volume":"3","author":"Russell","year":"2014","journal-title":"elife"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/oxfordjournals.epirev.a017917","article-title":"Emerging infections: Pandemic influenza","volume":"18","author":"Glezen","year":"1996","journal-title":"Epidemiol. 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