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      Novel reassortant 2.3.4.4B H5N6 highly pathogenic avian influenza viruses circulating among wild, domestic birds in Xinjiang, Northwest China

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          Abstract

          Background

          The H5 avian influenza viruses (AIVs) of clade 2.3.4.4 circulate in wild and domestic birds worldwide. In 2017, nine strains of H5N6 AIVs were isolated from aquatic poultry in Xinjiang, Northwest China.

          Objectives

          This study aimed to analyze the origin, reassortment, and mutations of the AIV isolates.

          Methods

          AIVs were isolated from oropharyngeal and cloacal swabs of poultry. Identification was accomplished by inoculating isolates into embryonated chicken eggs and performing hemagglutination tests and reverse transcription polymerase chain reaction (RT-PCR). The viral genomes were amplified with RT-PCR and then sequenced. The sequence alignment, phylogenetic, and molecular characteristic analyses were performed by using bioinformatic software.

          Results

          Nine isolates originated from the same ancestor. The viral HA gene belonged to clade 2.3.4.4B, while the NA gene had a close phylogenetic relationship with the 2.3.4.4C H5N6 highly pathogenic avian influenza viruses (HPAIVs) isolated from shoveler ducks in Ningxia in 2015. The NP gene was grouped into an independent subcluster within the 2.3.4.4B H5N8 AIVs, and the remaining six genes all had close phylogenetic relationships with the 2.3.4.4B H5N8 HPAIVs isolated from the wild birds in China, Egypt, Uganda, Cameroon, and India in 2016–2017, Multiple basic amino acid residues associated with HPAIVs were located adjacent to the cleavage site of the HA protein. The nine isolates comprised reassortant 2.3.4.4B HPAIVs originating from 2.3.4.4B H5N8 and 2.3.4.4C H5N6 viruses in wild birds.

          Conclusions

          These results suggest that the Northern Tianshan Mountain wetlands in Xinjiang may have a key role in AIVs disseminating from Central China to the Eurasian continent and East African.

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          Most cited references38

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          Influenza

          Influenza is an infectious respiratory disease that, in humans, is caused by influenza A and influenza B viruses. Typically characterized by annual seasonal epidemics, sporadic pandemic outbreaks involve influenza A virus strains of zoonotic origin. The WHO estimates that annual epidemics of influenza result in ~1 billion infections, 3–5 million cases of severe illness and 300,000–500,000 deaths. The severity of pandemic influenza depends on multiple factors, including the virulence of the pandemic virus strain and the level of pre-existing immunity. The most severe influenza pandemic, in 1918, resulted in >40 million deaths worldwide. Influenza vaccines are formulated every year to match the circulating strains, as they evolve antigenically owing to antigenic drift. Nevertheless, vaccine efficacy is not optimal and is dramatically low in the case of an antigenic mismatch between the vaccine and the circulating virus strain. Antiviral agents that target the influenza virus enzyme neuraminidase have been developed for prophylaxis and therapy. However, the use of these antivirals is still limited. Emerging approaches to combat influenza include the development of universal influenza virus vaccines that provide protection against antigenically distant influenza viruses, but these vaccines need to be tested in clinical trials to ascertain their effectiveness.
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            Role for migratory wild birds in the global spread of avian influenza H5N8.

            (2016)
            Avian influenza viruses affect both poultry production and public health. A subtype H5N8 (clade 2.3.4.4) virus, following an outbreak in poultry in South Korea in January 2014, rapidly spread worldwide in 2014-2015. Our analysis of H5N8 viral sequences, epidemiological investigations, waterfowl migration, and poultry trade showed that long-distance migratory birds can play a major role in the global spread of avian influenza viruses. Further, we found that the hemagglutinin of clade 2.3.4.4 virus was remarkably promiscuous, creating reassortants with multiple neuraminidase subtypes. Improving our understanding of the circumpolar circulation of avian influenza viruses in migratory waterfowl will help to provide early warning of threats from avian influenza to poultry, and potentially human, health.
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              Lethal H5N1 influenza viruses escape host anti-viral cytokine responses.

              The H5N1 influenza viruses transmitted to humans in 1997 were highly virulent, but the mechanism of their virulence in humans is largely unknown. Here we show that lethal H5N1 influenza viruses, unlike other human, avian and swine influenza viruses, are resistant to the antiviral effects of interferons and tumor necrosis factor alpha. The nonstructural (NS) gene of H5N1 viruses is associated with this resistance. Pigs infected with recombinant human H1N1 influenza virus that carried the H5N1 NS gene experienced significantly greater and more prolonged viremia, fever and weight loss than did pigs infected with wild-type human H1N1 influenza virus. These effects required the presence of glutamic acid at position 92 of the NS1 molecule. These findings may explain the mechanism of the high virulence of H5N1 influenza viruses in humans.
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                Author and article information

                Journal
                J Vet Sci
                J Vet Sci
                JVS
                Journal of Veterinary Science
                The Korean Society of Veterinary Science
                1229-845X
                1976-555X
                July 2021
                11 May 2021
                : 22
                : 4
                : e43
                Affiliations
                [1 ]Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830046, China.
                [2 ]CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Science, Beijing 100101, China.
                [3 ]Key Laboratory of Etiology and Emerging infections Disease in Shandong First Medical University, Taian 271016, China.
                Author notes
                Corresponding authors: Zhenghai Ma. Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830046, China. mzhxju@ 123456126.com
                Corresponding authors: Yuhai Bi. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Science, Beijing 100101, China. beeyh@ 123456im.ac.cn

                Qian Zhang and Xindi Mei contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-2858-4840
                https://orcid.org/0000-0002-7825-2254
                https://orcid.org/0000-0002-4900-231X
                https://orcid.org/0000-0001-9628-4850
                https://orcid.org/0000-0003-4261-1187
                https://orcid.org/0000-0001-6727-723X
                https://orcid.org/0000-0002-8717-2942
                https://orcid.org/0000-0002-5595-363X
                https://orcid.org/0000-0002-0930-7696
                Article
                10.4142/jvs.2021.22.e43
                8318794
                34170087
                6265cc17-61be-47a5-897c-ac389a0fd27b
                © 2021 The Korean Society of Veterinary Science

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 February 2021
                : 18 April 2021
                : 28 April 2021
                Funding
                Funded by: Xinjiang Uygur Autonomous Region Regional Cooperative Innovation Project;
                Award ID: 2017E01022
                Funded by: National Major Science and Technology Projects of China, CrossRef https://doi.org/10.13039/501100013076;
                Award ID: 2018ZX10101004
                Categories
                Original Article
                Virology

                Veterinary medicine
                highly pathogenic avian influenza virus,h5n6,reassortant,poultry,wild bird
                Veterinary medicine
                highly pathogenic avian influenza virus, h5n6, reassortant, poultry, wild bird

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