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      First genome report and analysis of chicken H7N9 influenza viruses with poly-basic amino acids insertion in the hemagglutinin cleavage site

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          Abstract

          We report the full-length sequence of two chicken source influenza A (H7N9) viruses found in Guangdong live poultry market (LPM) during the most recent wave of human infections (from October 2016 to the present time). These viruses carry insertion of poly-basic amino acids (KGKRTAR/G) at the protease cleavage site of the HA protein, which were previously found in the highly pathogenic (HP) human influenza A (H7N9) [IAV(H7N9)] strains. Phylogenetic analysis of these two novel avian influenza viruses (AIVs) suggested that their genomes reassorted between the Yangtze River Delta (YRD) and Pearl River Delta (PRD) clades. Molecular clock analysis indicated that they emerged several months before the HP human strains. Collectively, our results suggest that IAV(H7N9) viruses evolve in chickens through antigenic drift to include a signature HP sequence in the HA gene, which highlights challenges in risk assessment and public health management of IAV(H7N9) infections at the human-animal interface.

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          Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses.

          M Hatta (2001)
          In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. When mice were infected with the human isolates, two virulence groups became apparent. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice. Moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.
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            Choosing appropriate substitution models for the phylogenetic analysis of protein-coding sequences.

            Beth Shapiro, Andrew Rambaut, Alexei J. Drummond (2006)
            Although phylogenetic inference of protein-coding sequences continues to dominate the literature, few analyses incorporate evolutionary models that consider the genetic code. This problem is exacerbated by the exclusion of codon-based models from commonly employed model selection techniques, presumably due to the computational cost associated with codon models. We investigated an efficient alternative to standard nucleotide substitution models, in which codon position (CP) is incorporated into the model. We determined the most appropriate model for alignments of 177 RNA virus genes and 106 yeast genes, using 11 substitution models including one codon model and four CP models. The majority of analyzed gene alignments are best described by CP substitution models, rather than by standard nucleotide models, and without the computational cost of full codon models. These results have significant implications for phylogenetic inference of coding sequences as they make it clear that substitution models incorporating CPs not only are a computationally realistic alternative to standard models but may also frequently be statistically superior.
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              Lethal H5N1 influenza viruses escape host anti-viral cytokine responses.

              Sang Seo, Erich Hoffmann, Robert G. Webster (2002)
              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

                Contributors
                Hinh Ly: hly@umn.edu
                Jianhong Chen: jianhongchen.fsu@gmail.com
                Journal
                Journal ID (nlm-ta): Sci Rep
                Journal ID (iso-abbrev): Sci Rep
                Title: Scientific Reports
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2045-2322
                Publication date (Electronic): 30 August 2017
                Publication date PMC-release: 30 August 2017
                Publication date Collection: 2017
                Volume: 7
                Electronic Location Identifier: 9972
                Affiliations
                [1 ]GRID grid.443369.f, School of Life Science and Engineering, Foshan University, ; Foshan, China
                [2 ]Department of Veterinary & Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Twin Cities, Minnesota USA
                [3 ]ISNI 0000 0000 8653 1072, GRID grid.410737.6, Department of Pathogenic Biology and Immunology, , Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, ; Guangdong, China
                [4 ]GRID grid.430328.e, Shanghai Municipal Center for Disease Control and Prevention (SCDC), ; Shanghai, China
                Article
                Publisher ID: 10605
                DOI: 10.1038/s41598-017-10605-6
                PMC ID: 5577273
                PubMed ID: 28855633
                SO-VID: 6c10a437-4386-43cc-8682-5c6f72399612
                Copyright © © The Author(s) 2017
                License:

                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
                Date received : 16 May 2017
                Date accepted : 10 August 2017
                Categories
                Subject: Article
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                issue-copyright-statement © The Author(s) 2017

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