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      Sudden emergence of human infections with H7N9 avian influenza A virus in Hubei province, central China

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          Abstract

          There have been five waves of H7N9 avian influenza virus (AIV) infection in humans since its initial emergence in China in 2013, posing a significant threat to public health. Hubei province was free local transmission during the first four waves of H7N9 AIV. However, multiple cases of human H7N9 infection were reported in Hubei during January 2017. To understand the molecular epidemiology that underlies this sudden emergence, we collected samples from 14 human cases of H7N9 influenza virus from Hubei province, along with environmental samples from different locations in Hubei. Our analysis revealed that the newly emerged human H7N9 viruses were all from persons exposed to poultry and shared the same origin as the environmental sampled viruses in the Yangtze River lineage of H7N9. Notably, we also documented an earlier and distinct importation from Jiangsu province that may have established a local environmental reservoir. Our study highlights the need for continued surveillance of H7N9 in both human and avian populations in central China.

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          Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus

          New England Journal of Medicine, 368(20), 1888-1897
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            A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice.

            In this study, we explored the molecular basis determining the virulence of H5N1 avian influenza viruses in mammalian hosts by comparing two viruses, A/Duck/Guangxi/12/03 (DK/12) and A/Duck/Guangxi/27/03 (DK/27), which are genetically similar but differ in their pathogenicities in mice. To assess the genetic basis for this difference in virulence, we used reverse genetics to generate a series of reassortants and mutants of these two viruses. We found that a single-amino-acid substitution of serine for proline at position 42 (P42S) in the NS1 protein dramatically increased the virulence of the DK/12 virus in mice, whereas the substitution of proline for serine at the same position (S42P) completely attenuated the DK/27 virus. We further demonstrated that the amino acid S42 of NS1 is critical for the H5N1 influenza virus to antagonize host cell interferon induction and for the NS1 protein to prevent the double-stranded RNA-mediated activation of the NF-kappaB pathway and the IRF-3 pathway. Our results indicate that the NS1 protein is critical for the pathogenicity of H5N1 influenza viruses in mammalian hosts and that the amino acid S42 of NS1 plays a key role in undermining the antiviral immune response of the host cell.
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              Two Outbreak Sources of Influenza A (H7N9) Viruses Have Been Established in China.

              Due to enzootic infections in poultry and persistent human infections in China, influenza A (H7N9) virus has remained a public health threat. The Yangtze River Delta region, which is located in eastern China, is well recognized as the original source for H7N9 outbreaks. Based on the evolutionary analysis of H7N9 viruses from all three outbreak waves since 2013, we identified the Pearl River Delta region as an additional H7N9 outbreak source. H7N9 viruses are repeatedly introduced from these two sources to the other areas, and the persistent circulation of H7N9 viruses occurs in poultry, causing continuous outbreak waves. Poultry movements may contribute to the geographic expansion of the virus. In addition, the AnH1 genotype, which was predominant during wave 1, was replaced by JS537, JS18828, and AnH1887 genotypes during waves 2 and 3. The establishment of a new source and the continuous evolution of the virus hamper the elimination of H7N9 viruses, thus posing a long-term threat of H7N9 infection in humans. Therefore, both surveillance of H7N9 viruses in humans and poultry and supervision of poultry movements should be strengthened.
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                Author and article information

                Contributors
                jiecui@wh.iov.cn
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                6 February 2018
                6 February 2018
                2018
                : 8
                : 2486
                Affiliations
                [1 ]Hubei Provincial Center for Disease Control and Prevention, Wuhan, 430079 China
                [2 ]ISNI 0000000119573309, GRID grid.9227.e, CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, , Chinese Academy of Sciences, ; Wuhan, 430071 China
                [3 ]ISNI 0000 0004 1797 8419, GRID grid.410726.6, University of Chinese Academy of Sciences, ; Beijing, 100049 China
                [4 ]ISNI 0000 0000 8910 6733, GRID grid.410638.8, Institute of Pathogen Biology, , Taishan Medical College, ; Taian, Shandong 271000 China
                [5 ]ISNI 0000000119573309, GRID grid.9227.e, Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, ; Beijing, 100101 China
                [6 ]ISNI 0000 0004 0627 1442, GRID grid.458488.d, CAS Key Laboratory of Pathogenic Microbiology and Immunology, , Institute of Microbiology, Chinese Academy of Sciences, ; Beijing, 100101 China
                [7 ]ISNI 0000 0004 1797 8419, GRID grid.410726.6, Savid Medical School, , University of Chinese Academy of Sciences, ; Beijing, 101408 China
                [8 ]ISNI 0000 0004 1936 834X, GRID grid.1013.3, Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, , The University of Sydney, ; Sydney, New South Wales Australia
                Author information
                http://orcid.org/0000-0002-8717-2942
                http://orcid.org/0000-0003-3693-2726
                http://orcid.org/0000-0001-9596-3552
                Article
                20988
                10.1038/s41598-018-20988-9
                5802767
                29410505
                f4d73f0f-6a71-41f9-94c2-b7665841516e
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 25 July 2017
                : 29 January 2018
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