A unique feature of swine ANP32A provides susceptibility to avian influenza virus infection in pigs
Identifieur interne : 000B97 ( Pmc/Curation ); précédent : 000B96; suivant : 000B98A unique feature of swine ANP32A provides susceptibility to avian influenza virus infection in pigs
Auteurs : Haili Zhang [République populaire de Chine] ; Hongxin Li [République populaire de Chine] ; Wenqiang Wang [République populaire de Chine] ; Yujie Wang [République populaire de Chine] ; Guan-Zhu Han [République populaire de Chine] ; Hualan Chen [République populaire de Chine] ; Xiaojun Wang [République populaire de Chine]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2020.
Abstract
Both the replication and transcription of the influenza virus are catalyzed by the viral polymerase complex. The polymerases of most avian influenza A viruses have poor performance in mammalian cells, which is considered to be one of the important species barriers. Pigs have been long considered as important intermediate hosts for interspecies transmission of the avian influenza virus, because of their susceptibility to infection with both avian and mammalian influenza viruses. However, the molecular basis of influenza polymerase adaptation in pigs remains largely unknown. ANP32A and ANP32B proteins have been identified as playing fundamental roles in influenza virus replication and host range determination. In this study, we found that swine ANP32A (swANP32A), unlike swine ANP32B or other mammalian ANP32A or B, shows stronger supporting activity to avian viral polymerase. Knockout of ANP32A in pig cells PK15 dramatically reduced avian influenza polymerase activity and viral infectivity, suggesting a unique feature of swANP32A in supporting avian influenza viral polymerase. This species-specific activity is mapped to two key sites, 106V and 156S, in swANP32A. Interestingly, the amino acid 106V is unique to pigs among all the vertebrate species studied, and when combined with 156S, exhibits positive epistasis in pigs. Mutation of 106V and 156S to the signature found in ANP32As from other mammalian species weakened the interaction between swANP32A and chicken viral polymerase, and reduced polymerase activity. Understanding the molecular basis of ANP32 proteins may help to discover new antiviral targets and design avian influenza resistant genome edited pigs.
Url:
DOI: 10.1371/journal.ppat.1008330
PubMed: 32084248
PubMed Central: 7055917
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000B97
Links to Exploration step
PMC:7055917Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A unique feature of swine ANP32A provides susceptibility to avian influenza virus infection in pigs</title><author><name sortKey="Zhang, Haili" sort="Zhang, Haili" uniqKey="Zhang H" first="Haili" last="Zhang">Haili Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin</wicri:regionArea></affiliation></author><author><name sortKey="Li, Hongxin" sort="Li, Hongxin" uniqKey="Li H" first="Hongxin" last="Li">Hongxin Li</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Wenqiang" sort="Wang, Wenqiang" uniqKey="Wang W" first="Wenqiang" last="Wang">Wenqiang Wang</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yujie" sort="Wang, Yujie" uniqKey="Wang Y" first="Yujie" last="Wang">Yujie Wang</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin</wicri:regionArea></affiliation></author><author><name sortKey="Han, Guan Zhu" sort="Han, Guan Zhu" uniqKey="Han G" first="Guan-Zhu" last="Han">Guan-Zhu Han</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Hualan" sort="Chen, Hualan" uniqKey="Chen H" first="Hualan" last="Chen">Hualan Chen</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Xiaojun" sort="Wang, Xiaojun" uniqKey="Wang X" first="Xiaojun" last="Wang">Xiaojun Wang</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32084248</idno><idno type="pmc">7055917</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055917</idno><idno type="RBID">PMC:7055917</idno><idno type="doi">10.1371/journal.ppat.1008330</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000B97</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B97</idno><idno type="wicri:Area/Pmc/Curation">000B97</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B97</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A unique feature of swine ANP32A provides susceptibility to avian influenza virus infection in pigs</title><author><name sortKey="Zhang, Haili" sort="Zhang, Haili" uniqKey="Zhang H" first="Haili" last="Zhang">Haili Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin</wicri:regionArea></affiliation></author><author><name sortKey="Li, Hongxin" sort="Li, Hongxin" uniqKey="Li H" first="Hongxin" last="Li">Hongxin Li</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Wenqiang" sort="Wang, Wenqiang" uniqKey="Wang W" first="Wenqiang" last="Wang">Wenqiang Wang</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yujie" sort="Wang, Yujie" uniqKey="Wang Y" first="Yujie" last="Wang">Yujie Wang</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin</wicri:regionArea></affiliation></author><author><name sortKey="Han, Guan Zhu" sort="Han, Guan Zhu" uniqKey="Han G" first="Guan-Zhu" last="Han">Guan-Zhu Han</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Hualan" sort="Chen, Hualan" uniqKey="Chen H" first="Hualan" last="Chen">Hualan Chen</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Xiaojun" sort="Wang, Xiaojun" uniqKey="Wang X" first="Xiaojun" last="Wang">Xiaojun Wang</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Both the replication and transcription of the influenza virus are catalyzed by the viral polymerase complex. The polymerases of most avian influenza A viruses have poor performance in mammalian cells, which is considered to be one of the important species barriers. Pigs have been long considered as important intermediate hosts for interspecies transmission of the avian influenza virus, because of their susceptibility to infection with both avian and mammalian influenza viruses. However, the molecular basis of influenza polymerase adaptation in pigs remains largely unknown. ANP32A and ANP32B proteins have been identified as playing fundamental roles in influenza virus replication and host range determination. In this study, we found that swine ANP32A (swANP32A), unlike swine ANP32B or other mammalian ANP32A or B, shows stronger supporting activity to avian viral polymerase. Knockout of ANP32A in pig cells PK15 dramatically reduced avian influenza polymerase activity and viral infectivity, suggesting a unique feature of swANP32A in supporting avian influenza viral polymerase. This species-specific activity is mapped to two key sites, 106V and 156S, in swANP32A. Interestingly, the amino acid 106V is unique to pigs among all the vertebrate species studied, and when combined with 156S, exhibits positive epistasis in pigs. Mutation of 106V and 156S to the signature found in ANP32As from other mammalian species weakened the interaction between swANP32A and chicken viral polymerase, and reduced polymerase activity. Understanding the molecular basis of ANP32 proteins may help to discover new antiviral targets and design avian influenza resistant genome edited pigs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author><author><name sortKey="Krauss, S" uniqKey="Krauss S">S Krauss</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scholtissek, C" uniqKey="Scholtissek C">C Scholtissek</name></author><author><name sortKey="Rohde, W" uniqKey="Rohde W">W Rohde</name></author><author><name sortKey="Von Hoyningen, V" uniqKey="Von Hoyningen V">V Von Hoyningen</name></author><author><name sortKey="Rott, R" uniqKey="Rott R">R Rott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garten, Rj" uniqKey="Garten R">RJ Garten</name></author><author><name sortKey="Davis, Ct" uniqKey="Davis C">CT Davis</name></author><author><name sortKey="Russell, Ca" uniqKey="Russell C">CA Russell</name></author><author><name sortKey="Shu, B" uniqKey="Shu B">B Shu</name></author><author><name sortKey="Lindstrom, S" uniqKey="Lindstrom S">S Lindstrom</name></author><author><name sortKey="Balish, A" uniqKey="Balish A">A Balish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author><author><name sortKey="Laver, Wg" uniqKey="Laver W">WG Laver</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dunham, Ej" uniqKey="Dunham E">EJ Dunham</name></author><author><name sortKey="Dugan, Vg" uniqKey="Dugan V">VG Dugan</name></author><author><name sortKey="Kaser, Ek" uniqKey="Kaser E">EK Kaser</name></author><author><name sortKey="Perkins, Se" uniqKey="Perkins S">SE Perkins</name></author><author><name sortKey="Brown, Ih" uniqKey="Brown I">IH Brown</name></author><author><name sortKey="Holmes, Ec" uniqKey="Holmes E">EC Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, W" uniqKey="Ma W">W Ma</name></author><author><name sortKey="Lager, Km" uniqKey="Lager K">KM Lager</name></author><author><name sortKey="Vincent, Al" uniqKey="Vincent A">AL Vincent</name></author><author><name sortKey="Janke, Bh" uniqKey="Janke B">BH Janke</name></author><author><name sortKey="Gramer, Mr" uniqKey="Gramer M">MR Gramer</name></author><author><name sortKey="Richt, Ja" uniqKey="Richt J">JA Richt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Richt, Wmrekja" uniqKey="Richt W">WMREKJA Richt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shinde, V" uniqKey="Shinde V">V Shinde</name></author><author><name sortKey="Bridges, Cb" uniqKey="Bridges C">CB Bridges</name></author><author><name sortKey="Uyeki, Tm" uniqKey="Uyeki T">TM Uyeki</name></author><author><name sortKey="Shu, B" uniqKey="Shu B">B Shu</name></author><author><name sortKey="Balish, A" uniqKey="Balish A">A Balish</name></author><author><name sortKey="Xu, X" uniqKey="Xu X">X Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="C, S" uniqKey="C S">S C</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neumann, G" uniqKey="Neumann G">G Neumann</name></author><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Long, Js" uniqKey="Long J">JS Long</name></author><author><name sortKey="Mistry, B" uniqKey="Mistry B">B Mistry</name></author><author><name sortKey="Haslam, Sm" uniqKey="Haslam S">SM Haslam</name></author><author><name sortKey="Barclay, Ws" uniqKey="Barclay W">WS Barclay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Imai, M" uniqKey="Imai M">M Imai</name></author><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sreenivasan, Cc" uniqKey="Sreenivasan C">CC Sreenivasan</name></author><author><name sortKey="Thomas, M" uniqKey="Thomas M">M Thomas</name></author><author><name sortKey="Antony, L" uniqKey="Antony L">L Antony</name></author><author><name sortKey="Wormstadt, T" uniqKey="Wormstadt T">T Wormstadt</name></author><author><name sortKey="Hildreth, Mb" uniqKey="Hildreth M">MB Hildreth</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ito, T" uniqKey="Ito T">T Ito</name></author><author><name sortKey="Couceiro, Jn" uniqKey="Couceiro J">JN Couceiro</name></author><author><name sortKey="Kelm, S" uniqKey="Kelm S">S Kelm</name></author><author><name sortKey="Baum, Lg" uniqKey="Baum L">LG Baum</name></author><author><name sortKey="Krauss, S" uniqKey="Krauss S">S Krauss</name></author><author><name sortKey="Castrucci, Mr" uniqKey="Castrucci M">MR Castrucci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Te, Vaj" uniqKey="Te V">VAJ Te</name></author><author><name sortKey="Fodor, E" uniqKey="Fodor E">E Fodor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eisfeld, Aj" uniqKey="Eisfeld A">AJ Eisfeld</name></author><author><name sortKey="Neumann, G" uniqKey="Neumann G">G Neumann</name></author><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Naffakh, N" uniqKey="Naffakh N">N Naffakh</name></author><author><name sortKey="Massin, P" uniqKey="Massin P">P Massin</name></author><author><name sortKey="Escriou, N" uniqKey="Escriou N">N Escriou</name></author><author><name sortKey="Crescenzo Chaigne, B" uniqKey="Crescenzo Chaigne B">B Crescenzo-Chaigne</name></author><author><name sortKey="Van Der Werf, S" uniqKey="Van Der Werf S">S van der Werf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Salomon, R" uniqKey="Salomon R">R Salomon</name></author><author><name sortKey="Franks, J" uniqKey="Franks J">J Franks</name></author><author><name sortKey="Govorkova, Ea" uniqKey="Govorkova E">EA Govorkova</name></author><author><name sortKey="Ilyushina, Na" uniqKey="Ilyushina N">NA Ilyushina</name></author><author><name sortKey="Yen, Hl" uniqKey="Yen H">HL Yen</name></author><author><name sortKey="Hulse Post, Dj" uniqKey="Hulse Post D">DJ Hulse-Post</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hatta, M" uniqKey="Hatta M">M Hatta</name></author><author><name sortKey="Hatta, Y" uniqKey="Hatta Y">Y Hatta</name></author><author><name sortKey="Kim, Jh" uniqKey="Kim J">JH Kim</name></author><author><name sortKey="Watanabe, S" uniqKey="Watanabe S">S Watanabe</name></author><author><name sortKey="Shinya, K" uniqKey="Shinya K">K Shinya</name></author><author><name sortKey="Lien, Tnps" uniqKey="Lien T">TNPS Lien</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Labadie, K" uniqKey="Labadie K">K Labadie</name></author><author><name sortKey="Afonso, Ed" uniqKey="Afonso E">ED Afonso</name></author><author><name sortKey="Rameix Welti, Ma" uniqKey="Rameix Welti M">MA Rameix-Welti</name></author><author><name sortKey="Van Der Werf, S" uniqKey="Van Der Werf S">S van der Werf</name></author><author><name sortKey="Naffakh, N" uniqKey="Naffakh N">N Naffakh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mehle, A" uniqKey="Mehle A">A Mehle</name></author><author><name sortKey="Doudna, Ja" uniqKey="Doudna J">JA Doudna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rameix Welti, Ma" uniqKey="Rameix Welti M">MA Rameix-Welti</name></author><author><name sortKey="Tomoiu, A" uniqKey="Tomoiu A">A Tomoiu</name></author><author><name sortKey="Dos Santos Afonso, E" uniqKey="Dos Santos Afonso E">E Dos Santos Afonso</name></author><author><name sortKey="Van Der Werf, S" uniqKey="Van Der Werf S">S van der Werf</name></author><author><name sortKey="Naffakh, N" uniqKey="Naffakh N">N Naffakh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Manz, B" uniqKey="Manz B">B Manz</name></author><author><name sortKey="Brunotte, L" uniqKey="Brunotte L">L Brunotte</name></author><author><name sortKey="Reuther, P" uniqKey="Reuther P">P Reuther</name></author><author><name sortKey="Schwemmle, M" uniqKey="Schwemmle M">M Schwemmle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Subbarao, Ek" uniqKey="Subbarao E">EK Subbarao</name></author><author><name sortKey="London, W" uniqKey="London W">W London</name></author><author><name sortKey="Murphy, Br" uniqKey="Murphy B">BR Murphy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gabriel, G" uniqKey="Gabriel G">G Gabriel</name></author><author><name sortKey="Dauber, B" uniqKey="Dauber B">B Dauber</name></author><author><name sortKey="Wolff, T" uniqKey="Wolff T">T Wolff</name></author><author><name sortKey="Planz, O" uniqKey="Planz O">O Planz</name></author><author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name></author><author><name sortKey="Stech, J" uniqKey="Stech J">J Stech</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Q" uniqKey="Zhang Q">Q Zhang</name></author><author><name sortKey="Shi, J" uniqKey="Shi J">J Shi</name></author><author><name sortKey="Deng, G" uniqKey="Deng G">G Deng</name></author><author><name sortKey="Guo, J" uniqKey="Guo J">J Guo</name></author><author><name sortKey="Zeng, X" uniqKey="Zeng X">X Zeng</name></author><author><name sortKey="He, X" uniqKey="He X">X He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mehle, A" uniqKey="Mehle A">A Mehle</name></author><author><name sortKey="Doudna, Ja" uniqKey="Doudna J">JA Doudna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mehle, A" uniqKey="Mehle A">A Mehle</name></author><author><name sortKey="Dugan, Vg" uniqKey="Dugan V">VG Dugan</name></author><author><name sortKey="Taubenberger, Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author><author><name sortKey="Doudna, Ja" uniqKey="Doudna J">JA Doudna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zeng, Xy" uniqKey="Zeng X">XY Zeng</name></author><author><name sortKey="Tian, Gb" uniqKey="Tian G">GB Tian</name></author><author><name sortKey="Shi, Jz" uniqKey="Shi J">JZ Shi</name></author><author><name sortKey="Deng, Gh" uniqKey="Deng G">GH Deng</name></author><author><name sortKey="Li, Cj" uniqKey="Li C">CJ Li</name></author><author><name sortKey="Chen, Hl" uniqKey="Chen H">HL Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, Jz" uniqKey="Shi J">JZ Shi</name></author><author><name sortKey="Deng, Gh" uniqKey="Deng G">GH Deng</name></author><author><name sortKey="Ma, Sj" uniqKey="Ma S">SJ Ma</name></author><author><name sortKey="Zeng, Xy" uniqKey="Zeng X">XY Zeng</name></author><author><name sortKey="Yin, X" uniqKey="Yin X">X Yin</name></author><author><name sortKey="Li, M" uniqKey="Li M">M Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pensaert, M" uniqKey="Pensaert M">M Pensaert</name></author><author><name sortKey="Ottis, K" uniqKey="Ottis K">K Ottis</name></author><author><name sortKey="Vandeputte, J" uniqKey="Vandeputte J">J Vandeputte</name></author><author><name sortKey="Kaplan, Mm" uniqKey="Kaplan M">MM Kaplan</name></author><author><name sortKey="Bachmann, Pa" uniqKey="Bachmann P">PA Bachmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author><author><name sortKey="Shortridge, Kf" uniqKey="Shortridge K">KF Shortridge</name></author><author><name sortKey="Krauss, S" uniqKey="Krauss S">S Krauss</name></author><author><name sortKey="Li, Ph" uniqKey="Li P">PH Li</name></author><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karasin, Ai" uniqKey="Karasin A">AI Karasin</name></author><author><name sortKey="Olsen, Cw" uniqKey="Olsen C">CW Olsen</name></author><author><name sortKey="Anderson, Ga" uniqKey="Anderson G">GA Anderson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author><author><name sortKey="Markwell, D" uniqKey="Markwell D">D Markwell</name></author><author><name sortKey="Ghose, P" uniqKey="Ghose P">P Ghose</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author><author><name sortKey="Shortridge, Kf" uniqKey="Shortridge K">KF Shortridge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karasin, Ai" uniqKey="Karasin A">AI Karasin</name></author><author><name sortKey="West, K" uniqKey="West K">K West</name></author><author><name sortKey="Carman, S" uniqKey="Carman S">S Carman</name></author><author><name sortKey="Olsen, Cw" uniqKey="Olsen C">CW Olsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, Ct" uniqKey="Xu C">CT Xu</name></author><author><name sortKey="Fan, Wx" uniqKey="Fan W">WX Fan</name></author><author><name sortKey="Wei, R" uniqKey="Wei R">R Wei</name></author><author><name sortKey="Zhao, Hk" uniqKey="Zhao H">HK Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, Yk" uniqKey="Choi Y">YK Choi</name></author><author><name sortKey="Nguyen, Td" uniqKey="Nguyen T">TD Nguyen</name></author><author><name sortKey="Ozaki, H" uniqKey="Ozaki H">H Ozaki</name></author><author><name sortKey="Webby, Rj" uniqKey="Webby R">RJ Webby</name></author><author><name sortKey="Puthavathana, P" uniqKey="Puthavathana P">P Puthavathana</name></author><author><name sortKey="Buranathal, C" uniqKey="Buranathal C">C Buranathal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, W" uniqKey="Ma W">W Ma</name></author><author><name sortKey="Vincent, Al" uniqKey="Vincent A">AL Vincent</name></author><author><name sortKey="Gramer, Mr" uniqKey="Gramer M">MR Gramer</name></author><author><name sortKey="Brockwell, Cb" uniqKey="Brockwell C">CB Brockwell</name></author><author><name sortKey="Lager, Km" uniqKey="Lager K">KM Lager</name></author><author><name sortKey="Janke, Bh" uniqKey="Janke B">BH Janke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bateman, Ac" uniqKey="Bateman A">AC Bateman</name></author><author><name sortKey="Busch, Mg" uniqKey="Busch M">MG Busch</name></author><author><name sortKey="Karasin, Ai" uniqKey="Karasin A">AI Karasin</name></author><author><name sortKey="Bovin, N" uniqKey="Bovin N">N Bovin</name></author><author><name sortKey="Olsen, Cw" uniqKey="Olsen C">CW Olsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, G" uniqKey="Zhang G">G Zhang</name></author><author><name sortKey="Kong, W" uniqKey="Kong W">W Kong</name></author><author><name sortKey="Qi, W" uniqKey="Qi W">W Qi</name></author><author><name sortKey="Long, Lp" uniqKey="Long L">LP Long</name></author><author><name sortKey="Cao, Z" uniqKey="Cao Z">Z Cao</name></author><author><name sortKey="Huang, L" uniqKey="Huang L">L Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gomaa, Mr" uniqKey="Gomaa M">MR Gomaa</name></author><author><name sortKey="Kandeil, A" uniqKey="Kandeil A">A Kandeil</name></author><author><name sortKey="El Shesheny, R" uniqKey="El Shesheny R">R El-Shesheny</name></author><author><name sortKey="Shehata, Mm" uniqKey="Shehata M">MM Shehata</name></author><author><name sortKey="Mckenzie, Pp" uniqKey="Mckenzie P">PP McKenzie</name></author><author><name sortKey="Webby, Rj" uniqKey="Webby R">RJ Webby</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kida, H" uniqKey="Kida H">H Kida</name></author><author><name sortKey="Ito, T" uniqKey="Ito T">T Ito</name></author><author><name sortKey="Yasuda, J" uniqKey="Yasuda J">J Yasuda</name></author><author><name sortKey="Shimizu, Y" uniqKey="Shimizu Y">Y Shimizu</name></author><author><name sortKey="Itakura, C" uniqKey="Itakura C">C Itakura</name></author><author><name sortKey="Shortridge, Kf" uniqKey="Shortridge K">KF Shortridge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bortz, E" uniqKey="Bortz E">E Bortz</name></author><author><name sortKey="Westera, L" uniqKey="Westera L">L Westera</name></author><author><name sortKey="Maamary, J" uniqKey="Maamary J">J Maamary</name></author><author><name sortKey="Steel, J" uniqKey="Steel J">J Steel</name></author><author><name sortKey="Albrecht, Ra" uniqKey="Albrecht R">RA Albrecht</name></author><author><name sortKey="Manicassamy, B" uniqKey="Manicassamy B">B Manicassamy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Watanabe, T" uniqKey="Watanabe T">T Watanabe</name></author><author><name sortKey="Kawakami, E" uniqKey="Kawakami E">E Kawakami</name></author><author><name sortKey="Shoemaker, Je" uniqKey="Shoemaker J">JE Shoemaker</name></author><author><name sortKey="Lopes, Tj" uniqKey="Lopes T">TJ Lopes</name></author><author><name sortKey="Matsuoka, Y" uniqKey="Matsuoka Y">Y Matsuoka</name></author><author><name sortKey="Tomita, Y" uniqKey="Tomita Y">Y Tomita</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sugiyama, K" uniqKey="Sugiyama K">K Sugiyama</name></author><author><name sortKey="Kawaguchi, A" uniqKey="Kawaguchi A">A Kawaguchi</name></author><author><name sortKey="Okuwaki, M" uniqKey="Okuwaki M">M Okuwaki</name></author><author><name sortKey="Nagata, K" uniqKey="Nagata K">K Nagata</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Long, Js" uniqKey="Long J">JS Long</name></author><author><name sortKey="Giotis, Es" uniqKey="Giotis E">ES Giotis</name></author><author><name sortKey="Moncorge, O" uniqKey="Moncorge O">O Moncorge</name></author><author><name sortKey="Frise, R" uniqKey="Frise R">R Frise</name></author><author><name sortKey="Mistry, B" uniqKey="Mistry B">B Mistry</name></author><author><name sortKey="James, J" uniqKey="James J">J James</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, H" uniqKey="Zhang H">H Zhang</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Staller, E" uniqKey="Staller E">E Staller</name></author><author><name sortKey="Sheppard, Cm" uniqKey="Sheppard C">CM Sheppard</name></author><author><name sortKey="Neasham, Pj" uniqKey="Neasham P">PJ Neasham</name></author><author><name sortKey="Mistry, B" uniqKey="Mistry B">B Mistry</name></author><author><name sortKey="Peacock, Tp" uniqKey="Peacock T">TP Peacock</name></author><author><name sortKey="Goldhill, Dh" uniqKey="Goldhill D">DH Goldhill</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Domingues, P" uniqKey="Domingues P">P Domingues</name></author><author><name sortKey="Hale, Bg" uniqKey="Hale B">BG Hale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baker, Sf" uniqKey="Baker S">SF Baker</name></author><author><name sortKey="Ledwith, Mp" uniqKey="Ledwith M">MP Ledwith</name></author><author><name sortKey="Mehle, A" uniqKey="Mehle A">A Mehle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Domingues, P" uniqKey="Domingues P">P Domingues</name></author><author><name sortKey="Eletto, D" uniqKey="Eletto D">D Eletto</name></author><author><name sortKey="Magnus, C" uniqKey="Magnus C">C Magnus</name></author><author><name sortKey="Turkington, Hl" uniqKey="Turkington H">HL Turkington</name></author><author><name sortKey="Schmutz, S" uniqKey="Schmutz S">S Schmutz</name></author><author><name sortKey="Zagordi, O" uniqKey="Zagordi O">O Zagordi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Long, Js" uniqKey="Long J">JS Long</name></author><author><name sortKey="Idoko Akoh, A" uniqKey="Idoko Akoh A">A Idoko-Akoh</name></author><author><name sortKey="Mistry, B" uniqKey="Mistry B">B Mistry</name></author><author><name sortKey="Goldhill, D" uniqKey="Goldhill D">D Goldhill</name></author><author><name sortKey="Staller, E" uniqKey="Staller E">E Staller</name></author><author><name sortKey="Schreyer, J" uniqKey="Schreyer J">J Schreyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baker, Sf" uniqKey="Baker S">SF Baker</name></author><author><name sortKey="Mehle, A" uniqKey="Mehle A">A Mehle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, C" uniqKey="Li C">C Li</name></author><author><name sortKey="Li, Cg" uniqKey="Li C">CG Li</name></author><author><name sortKey="Zhang, Ajx" uniqKey="Zhang A">AJX Zhang</name></author><author><name sortKey="To, Kkw" uniqKey="To K">KKW To</name></author><author><name sortKey="Lee, Acy" uniqKey="Lee A">ACY Lee</name></author><author><name sortKey="Zhu, Hs" uniqKey="Zhu H">HS Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Teng, Q" uniqKey="Teng Q">Q Teng</name></author><author><name sortKey="Xu, D" uniqKey="Xu D">D Xu</name></author><author><name sortKey="Shen, W" uniqKey="Shen W">W Shen</name></author><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q Liu</name></author><author><name sortKey="Rong, G" uniqKey="Rong G">G Rong</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neumann, G" uniqKey="Neumann G">G Neumann</name></author><author><name sortKey="Watanabe, T" uniqKey="Watanabe T">T Watanabe</name></author><author><name sortKey="Ito, H" uniqKey="Ito H">H Ito</name></author><author><name sortKey="Watanabe, S" uniqKey="Watanabe S">S Watanabe</name></author><author><name sortKey="Goto, H" uniqKey="Goto H">H Goto</name></author><author><name sortKey="Gao, P" uniqKey="Gao P">P Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hause, Bm" uniqKey="Hause B">BM Hause</name></author><author><name sortKey="Stine, Dl" uniqKey="Stine D">DL Stine</name></author><author><name sortKey="Sheng, Z" uniqKey="Sheng Z">Z Sheng</name></author><author><name sortKey="Wang, Z" uniqKey="Wang Z">Z Wang</name></author><author><name sortKey="Chakravarty, S" uniqKey="Chakravarty S">S Chakravarty</name></author><author><name sortKey="Simonson, Rr" uniqKey="Simonson R">RR Simonson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Su, S" uniqKey="Su S">S Su</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author><author><name sortKey="Zhao, Fr" uniqKey="Zhao F">FR Zhao</name></author><author><name sortKey="Chen, Jd" uniqKey="Chen J">JD Chen</name></author><author><name sortKey="Xie, Jx" uniqKey="Xie J">JX Xie</name></author><author><name sortKey="Chen, Zm" uniqKey="Chen Z">ZM Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reilly, Pt" uniqKey="Reilly P">PT Reilly</name></author><author><name sortKey="Yu, Y" uniqKey="Yu Y">Y Yu</name></author><author><name sortKey="Hamiche, A" uniqKey="Hamiche A">A Hamiche</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fan, H" uniqKey="Fan H">H Fan</name></author><author><name sortKey="Walker, Ap" uniqKey="Walker A">AP Walker</name></author><author><name sortKey="Carrique, L" uniqKey="Carrique L">L Carrique</name></author><author><name sortKey="Keown, Jr" uniqKey="Keown J">JR Keown</name></author><author><name sortKey="Serna Martin, I" uniqKey="Serna Martin I">I Serna Martin</name></author><author><name sortKey="Karia, D" uniqKey="Karia D">D Karia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cauldwell, Av" uniqKey="Cauldwell A">AV Cauldwell</name></author><author><name sortKey="Long, Js" uniqKey="Long J">JS Long</name></author><author><name sortKey="Moncorge, O" uniqKey="Moncorge O">O Moncorge</name></author><author><name sortKey="Barclay, Ws" uniqKey="Barclay W">WS Barclay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Reeth, K" uniqKey="Van Reeth K">K. Van Reeth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Zhang, H" uniqKey="Zhang H">H Zhang</name></author><author><name sortKey="Na, L" uniqKey="Na L">L Na</name></author><author><name sortKey="Du, C" uniqKey="Du C">C Du</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author><author><name sortKey="Zheng, Yh" uniqKey="Zheng Y">YH Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liang, L" uniqKey="Liang L">L Liang</name></author><author><name sortKey="Jiang, L" uniqKey="Jiang L">L Jiang</name></author><author><name sortKey="Li, J" uniqKey="Li J">J Li</name></author><author><name sortKey="Zhao, Q" uniqKey="Zhao Q">Q Zhao</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author><author><name sortKey="He, X" uniqKey="He X">X He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moncorge, O" uniqKey="Moncorge O">O Moncorge</name></author><author><name sortKey="Long, Js" uniqKey="Long J">JS Long</name></author><author><name sortKey="Cauldwell, Av" uniqKey="Cauldwell A">AV Cauldwell</name></author><author><name sortKey="Zhou, H" uniqKey="Zhou H">H Zhou</name></author><author><name sortKey="Lycett, Sj" uniqKey="Lycett S">SJ Lycett</name></author><author><name sortKey="Barclay, Ws" uniqKey="Barclay W">WS Barclay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hsu, Pd" uniqKey="Hsu P">PD Hsu</name></author><author><name sortKey="Scott, Da" uniqKey="Scott D">DA Scott</name></author><author><name sortKey="Weinstein, Ja" uniqKey="Weinstein J">JA Weinstein</name></author><author><name sortKey="Ran, Fa" uniqKey="Ran F">FA Ran</name></author><author><name sortKey="Konermann, S" uniqKey="Konermann S">S Konermann</name></author><author><name sortKey="Agarwala, V" uniqKey="Agarwala V">V Agarwala</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jinek, M" uniqKey="Jinek M">M Jinek</name></author><author><name sortKey="East, A" uniqKey="East A">A East</name></author><author><name sortKey="Cheng, A" uniqKey="Cheng A">A Cheng</name></author><author><name sortKey="Lin, S" uniqKey="Lin S">S Lin</name></author><author><name sortKey="Ma, Eb" uniqKey="Ma E">EB Ma</name></author><author><name sortKey="Doudna, J" uniqKey="Doudna J">J Doudna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muench, H" uniqKey="Muench H">H Muench</name></author><author><name sortKey="Reed, L" uniqKey="Reed L">L Reed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Katoh, K" uniqKey="Katoh K">K Katoh</name></author><author><name sortKey="Standley, Dm" uniqKey="Standley D">DM Standley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kalyaanamoorthy, S" uniqKey="Kalyaanamoorthy S">S Kalyaanamoorthy</name></author><author><name sortKey="Minh, Bq" uniqKey="Minh B">BQ Minh</name></author><author><name sortKey="Wong, Tkf" uniqKey="Wong T">TKF Wong</name></author><author><name sortKey="Von Haeseler, A" uniqKey="Von Haeseler A">A von Haeseler</name></author><author><name sortKey="Jermiin, Ls" uniqKey="Jermiin L">LS Jermiin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nguyen, Lt" uniqKey="Nguyen L">LT Nguyen</name></author><author><name sortKey="Schmidt, Ha" uniqKey="Schmidt H">HA Schmidt</name></author><author><name sortKey="Von Haeseler, A" uniqKey="Von Haeseler A">A von Haeseler</name></author><author><name sortKey="Minh, Bq" uniqKey="Minh B">BQ Minh</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Pathog</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Pathog</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plospath</journal-id><journal-title-group><journal-title>PLoS Pathogens</journal-title></journal-title-group><issn pub-type="ppub">1553-7366</issn><issn pub-type="epub">1553-7374</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32084248</article-id><article-id pub-id-type="pmc">7055917</article-id><article-id pub-id-type="doi">10.1371/journal.ppat.1008330</article-id><article-id pub-id-type="publisher-id">PPATHOGENS-D-19-01956</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Proteins</subject><subj-group><subject>DNA-binding proteins</subject><subj-group><subject>Polymerases</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Zoology</subject><subj-group><subject>Animal Diseases</subject><subj-group><subject>Animal Influenza</subject><subj-group><subject>Avian Influenza</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Infectious Diseases</subject><subj-group><subject>Zoonoses</subject><subj-group><subject>Avian Influenza</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Viruses</subject><subj-group><subject>RNA viruses</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Microbiology</subject><subj-group><subject>Medical microbiology</subject><subj-group><subject>Microbial pathogens</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and health sciences</subject><subj-group><subject>Pathology and laboratory medicine</subject><subj-group><subject>Pathogens</subject><subj-group><subject>Microbial pathogens</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Viruses</subject><subj-group><subject>Viral pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza viruses</subject><subj-group><subject>Influenza A virus</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Eukaryota</subject><subj-group><subject>Animals</subject><subj-group><subject>Vertebrates</subject><subj-group><subject>Amniotes</subject><subj-group><subject>Mammals</subject><subj-group><subject>Swine</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Microbiology</subject><subj-group><subject>Virology</subject><subj-group><subject>Viral Replication</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Viruses</subject><subj-group><subject>RNA viruses</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza Viruses</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Microbiology</subject><subj-group><subject>Medical Microbiology</subject><subj-group><subject>Microbial Pathogens</subject><subj-group><subject>Viral Pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza Viruses</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Pathology and Laboratory Medicine</subject><subj-group><subject>Pathogens</subject><subj-group><subject>Microbial Pathogens</subject><subj-group><subject>Viral Pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza Viruses</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Viruses</subject><subj-group><subject>Viral Pathogens</subject><subj-group><subject>Orthomyxoviruses</subject><subj-group><subject>Influenza Viruses</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Eukaryota</subject><subj-group><subject>Animals</subject><subj-group><subject>Vertebrates</subject><subj-group><subject>Amniotes</subject><subj-group><subject>Mammals</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Organisms</subject><subj-group><subject>Eukaryota</subject><subj-group><subject>Animals</subject><subj-group><subject>Vertebrates</subject><subj-group><subject>Amniotes</subject><subj-group><subject>Birds</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>A unique feature of swine ANP32A provides susceptibility to avian influenza virus infection in pigs</article-title><alt-title alt-title-type="running-head">Swine ANP32A supports avian influenza virus</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Haili</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Formal analysis</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Software</role><role content-type="http://credit.casrai.org/">Validation</role><role content-type="http://credit.casrai.org/">Writing – original draft</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Hongxin</given-names></name><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Wenqiang</given-names></name><role content-type="http://credit.casrai.org/">Software</role><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Yujie</given-names></name><role content-type="http://credit.casrai.org/">Resources</role><role content-type="http://credit.casrai.org/">Validation</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8352-7726</contrib-id><name><surname>Han</surname><given-names>Guan-Zhu</given-names></name><role content-type="http://credit.casrai.org/">Software</role><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Hualan</given-names></name><role content-type="http://credit.casrai.org/">Funding acquisition</role><role content-type="http://credit.casrai.org/">Resources</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-4521-4099</contrib-id><name><surname>Wang</surname><given-names>Xiaojun</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Funding acquisition</role><role content-type="http://credit.casrai.org/">Supervision</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China</addr-line></aff><aff id="aff002"><label>2</label><addr-line>College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Fodor</surname><given-names>Ervin</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>Oxford University, UNITED KINGDOM</addr-line></aff><author-notes><fn fn-type="COI-statement" id="coi001"><p>The authors have declared that no competing interests exist.</p></fn><corresp id="cor001">* E-mail: <email>wangxiaojun@caas.cn</email></corresp></author-notes><pub-date pub-type="epub"><day>21</day><month>2</month><year>2020</year></pub-date><pub-date pub-type="collection"><month>2</month><year>2020</year></pub-date><volume>16</volume><issue>2</issue><elocation-id>e1008330</elocation-id><history><date date-type="received"><day>17</day><month>10</month><year>2019</year></date><date date-type="accepted"><day>17</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 Zhang et al</copyright-statement><copyright-year>2020</copyright-year><copyright-holder>Zhang et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="ppat.1008330.pdf"></self-uri><abstract><p>Both the replication and transcription of the influenza virus are catalyzed by the viral polymerase complex. The polymerases of most avian influenza A viruses have poor performance in mammalian cells, which is considered to be one of the important species barriers. Pigs have been long considered as important intermediate hosts for interspecies transmission of the avian influenza virus, because of their susceptibility to infection with both avian and mammalian influenza viruses. However, the molecular basis of influenza polymerase adaptation in pigs remains largely unknown. ANP32A and ANP32B proteins have been identified as playing fundamental roles in influenza virus replication and host range determination. In this study, we found that swine ANP32A (swANP32A), unlike swine ANP32B or other mammalian ANP32A or B, shows stronger supporting activity to avian viral polymerase. Knockout of ANP32A in pig cells PK15 dramatically reduced avian influenza polymerase activity and viral infectivity, suggesting a unique feature of swANP32A in supporting avian influenza viral polymerase. This species-specific activity is mapped to two key sites, 106V and 156S, in swANP32A. Interestingly, the amino acid 106V is unique to pigs among all the vertebrate species studied, and when combined with 156S, exhibits positive epistasis in pigs. Mutation of 106V and 156S to the signature found in ANP32As from other mammalian species weakened the interaction between swANP32A and chicken viral polymerase, and reduced polymerase activity. Understanding the molecular basis of ANP32 proteins may help to discover new antiviral targets and design avian influenza resistant genome edited pigs.</p></abstract><abstract abstract-type="summary"><title>Author summary</title><p>The pig is considered to be a “mixing vessel” for influenza viruses because it can be infected by both human and avian influenza viruses. This mixing of viruses could potentially produce novel recombinant strains that are more adaptable to humans or other mammals. The permissive mechanism that allows pig cells to be infected with avian influenza virus is largely unknown. Here we reveal that the pig cellular protein ANP32A has a unique 106V/156S signature, different from that of ANP32A proteins from other mammals, enabling the protein to bind strongly to avian influenza polymerase at the post-entry step, and promoting avian virus replication. This species-specific 106V/156S epistasis of swANP32A likely determines the susceptibility of pigs to avian influenza infection. Our findings provide novel insights into the molecular basis of interspecies transmission of avian IAV between chickens and pigs.</p></abstract><funding-group><award-group id="award001"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/501100001809</institution-id><institution>National Natural Science Foundation of China</institution></institution-wrap></funding-source><award-id>31521005</award-id><principal-award-recipient><name><surname>Chen</surname><given-names>Hualan</given-names></name></principal-award-recipient></award-group><award-group id="award002"><funding-source><institution>Natural Science Foundation of Heilongjiang Province</institution></funding-source><award-id>JC2018010</award-id><principal-award-recipient><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-4521-4099</contrib-id><name><surname>Wang</surname><given-names>Xiaojun</given-names></name></principal-award-recipient></award-group><funding-statement>This work was supported by the grant from the Natural Science Foundation of China to HL Chen (No. 31521005) (<ext-link ext-link-type="uri" xlink:href="http://www.nsfc.gov.cn">www.nsfc.gov.cn</ext-link>) and the Natural Science Foundation of Heilongjiang Province to XJ Wang (No.JC2018010)(<ext-link ext-link-type="uri" xlink:href="http://jj.hljkj.cn/zr/">http://jj.hljkj.cn/zr/</ext-link>). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="9"></fig-count><table-count count="0"></table-count><page-count count="23"></page-count></counts><custom-meta-group><custom-meta><meta-name>PLOS Publication Stage</meta-name><meta-value>vor-update-to-uncorrected-proof</meta-value></custom-meta><custom-meta><meta-name>Publication Update</meta-name><meta-value>2020-03-04</meta-value></custom-meta><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are within the manuscript and its Supporting Information files.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are within the manuscript and its Supporting Information files.</p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000B97 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000B97 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= H2N2V1
|flux= Pmc
|étape= Curation
|type= RBID
|clé= PMC:7055917
|texte= A unique feature of swine ANP32A provides susceptibility to avian influenza virus infection in pigs
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:32084248" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \
| NlmPubMed2Wicri -a H2N2V1
| This area was generated with Dilib version V0.6.33. |  |