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      Could A Deletion in Neuraminidase Stalk Strengthen Human Tropism of the Novel Avian Influenza Virus H7N9 in China, 2013?

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          Abstract

          Objective. A novel avian influenza A virus (AIV) H7N9 subtype which emerged in China in 2013 caused worldwide concern. Deletion of amino-acids 69 to 73 in the neuraminidase stalk was its most notable characteristic. This study is aimed to discuss the tropism and virulence effects of this deletion. Methods: Neuraminidase gene sequences of N9 subtype were collected from NCBI and GISAID. MEGA6.0, Stata12.0, and UCSF Chimera were employed for sequence aligning, significance testing, and protein tertiary structure homology modeling. Results: A total of 736 sequences were obtained; there were 81 human isolates of the novel AIV H7N9, of which 79 had the deletion. Among all the 654 avian origin sequences, only 43 had the deletion ( p < 0.001). Tertiary structure displayed that the deletion obviously changed the spatial direction of neuraminidase. Conclusions: The deletion in neuraminidase stalk could have strengthened human tropism of the novel AIV H7N9, as well as its virulence.

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          Most cited references20

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          A single amino acid in the PB2 gene of influenza A virus is a determinant of host range.

          The single gene reassortant virus that derives its PB2 gene from the avian influenza A/Mallard/NY/78 virus and remaining genes from the human influenza A/Los Angeles/2/87 virus exhibits a host range restriction (hr) phenotype characterized by efficient replication in avian tissue and failure to produce plaques in mammalian Madin-Darby canine kidney cells. The hr phenotype is associated with restriction of viral replication in the respiratory tract of squirrel monkeys and humans. To identify the genetic basis of the hr phenotype, we isolated four phenotypic hr mutant viruses that acquired the ability to replicate efficiently in mammalian tissue. Segregational analysis indicated that the loss of the hr phenotype was due to a mutation in the PB2 gene itself. The nucleotide sequences of the PB2 gene of each of the four hr mutants revealed that a single amino acid substitution at position 627 (Glu-->Lys) was responsible for the restoration of the ability of the PB2 single gene reassortant to replicate in Madin-Darby canine kidney cells. Interestingly, the amino acid at position 627 in every avian influenza A virus PB2 protein analyzed to date is glutamic acid, and in every human influenza A virus PB2 protein, it is lysine. Thus, the amino acid at residue 627 of PB2 is an important determinant of host range of influenza A viruses.
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            Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China

            New England Journal of Medicine, 370(6), 520-532
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              Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus.

              The 1918 "Spanish" influenza pandemic represents the largest recorded outbreak of any infectious disease. The crystal structure of the uncleaved precursor of the major surface antigen of the extinct 1918 virus was determined at 3.0 angstrom resolution after reassembly of the hemagglutinin gene from viral RNA fragments preserved in 1918 formalin-fixed lung tissues. A narrow avian-like receptor-binding site, two previously unobserved histidine patches, and a less exposed surface loop at the cleavage site that activates viral membrane fusion reveal structural features primarily found in avian viruses, which may have contributed to the extraordinarily high infectivity and mortality rates observed during 1918.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                20 January 2015
                January 2015
                : 12
                : 1
                : 1020-1028
                Affiliations
                [1 ]Department of Sanitary Microbiology, School of Public Health, Fudan University, Shanghai 200032, China; E-Mails: chenliangfd@ 123456sina.com (L.C.); jianglufang@ 123456fudan.edu.cn (L.J.)
                [2 ]Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai 200032, China; E-Mails: epistat@ 123456gmail.com (Z.Z.); gmzhao@ 123456shmu.edu.cn (G.Z.); xiongchenglong1@ 123456sina.com (Q.J.)
                [3 ]Intensive Care Unit of Burn and Trauma Center, Changhai Hospital, Second Military Medical University, Shanghai 200433, China; E-Mail: z8160720@ 123456126.com
                [4 ]Department of Epidemiology and Biostatistics, School of Public Health, Fudan University, Shanghai 200032, China
                [5 ]Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, Ontario K1H 8M5, Canada; E-Mail: ychen@ 123456uottawa.ca
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Author to whom correspondence should be addressed; E-Mail: xiongchenglong@ 123456fudan.edu.cn ; Tel.: +86-021-5423-7237; Fax: +86-021-5423-7435.
                Article
                ijerph-12-01020
                10.3390/ijerph120101020
                4306908
                25608590
                0076d693-1ef4-41d2-a10c-dfde222bbed8
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 September 2014
                : 13 January 2015
                Categories
                Article

                Public health
                deletion,neuraminidase,h7n9,china
                Public health
                deletion, neuraminidase, h7n9, china

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