Mammalian-adaptive mutation NP-Q357K in Eurasian H1N1 Swine Influenza viruses determines the virulence phenotype in mice
Identifieur interne : 000057 ( Pmc/Checkpoint ); précédent : 000056; suivant : 000058Mammalian-adaptive mutation NP-Q357K in Eurasian H1N1 Swine Influenza viruses determines the virulence phenotype in mice
Auteurs : Wenfei Zhu [République populaire de Chine] ; Zhaomin Feng [République populaire de Chine] ; Yongkun Chen [République populaire de Chine] ; Lei Yang [République populaire de Chine] ; Jia Liu [République populaire de Chine] ; Xiyan Li [République populaire de Chine] ; Suli Liu [République populaire de Chine] ; Lijuan Zhou [République populaire de Chine] ; Hejiang Wei [République populaire de Chine] ; Rongbao Gao [République populaire de Chine] ; Dayan Wang [République populaire de Chine] ; Yuelong Shu [République populaire de Chine]Source :
- Emerging Microbes & Infections [ 2222-1751 ] ; 2019.
Abstract
It has recently been proposed that the Eurasian avian-like H1N1 (EA H1N1) swine influenza virus (SIV) is one of the most likely zoonotic viruses to cause the next influenza pandemic. Two main genotypes EA H1N1 viruses have been recognized to be infected humans in China. Our study finds that one of the genotypes JS1-like viruses are avirulent in mice. However, the other are HuN-like viruses and are virulent in mice. The molecular mechanism underlying this difference shows that the NP gene determines the virulence of the EA H1N1 viruses in mice. In addition, a single substitution, Q357K, in the NP protein of the EA H1N1 viruses alters the virulence phenotype. This substitution is a typical human signature marker, which is prevalent in human viruses but rarely detected in avian influenza viruses. The NP-Q357K substitution is readily to be occurred when avian influenza viruses circulate in pigs, and may facilitate their infection of humans and allow viruses also carrying NP-357K to circulate in humans. Our study demonstrates that the substitution Q357K in the NP protein plays a key role in the virulence phenotype of EA H1N1 SIVs, and provides important information for evaluating the pandemic risk of field influenza strains.
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DOI: 10.1080/22221751.2019.1635873
PubMed: 31267843
PubMed Central: 6609330
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xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Suli" sort="Liu, Suli" uniqKey="Liu S" first="Suli" last="Liu">Suli Liu</name><affiliation wicri:level="1"><nlm:aff id="AF3"><institution>School of Public Health (Shenzhen), Sun Yat-sen University</institution>, Guangdong,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Lijuan" sort="Zhou, Lijuan" uniqKey="Zhou L" first="Lijuan" last="Zhou">Lijuan Zhou</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wei, Hejiang" sort="Wei, Hejiang" uniqKey="Wei H" first="Hejiang" last="Wei">Hejiang Wei</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gao, Rongbao" sort="Gao, Rongbao" uniqKey="Gao R" first="Rongbao" last="Gao">Rongbao 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type="main">Mammalian-adaptive mutation NP-Q357K in Eurasian H1N1 Swine Influenza viruses determines the virulence phenotype in mice</title><author><name sortKey="Zhu, Wenfei" sort="Zhu, Wenfei" uniqKey="Zhu W" first="Wenfei" last="Zhu">Wenfei Zhu</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Feng, Zhaomin" sort="Feng, Zhaomin" uniqKey="Feng Z" first="Zhaomin" last="Feng">Zhaomin Feng</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yongkun" sort="Chen, Yongkun" uniqKey="Chen Y" first="Yongkun" last="Chen">Yongkun Chen</name><affiliation wicri:level="1"><nlm:aff id="AF3"><institution>School of Public Health (Shenzhen), Sun Yat-sen University</institution>, Guangdong,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Lei" sort="Yang, Lei" uniqKey="Yang L" first="Lei" last="Yang">Lei Yang</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Jia" sort="Liu, Jia" uniqKey="Liu J" first="Jia" last="Liu">Jia Liu</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Xiyan" sort="Li, Xiyan" uniqKey="Li X" first="Xiyan" last="Li">Xiyan Li</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Suli" sort="Liu, Suli" uniqKey="Liu S" first="Suli" last="Liu">Suli Liu</name><affiliation wicri:level="1"><nlm:aff id="AF3"><institution>School of Public Health (Shenzhen), Sun Yat-sen University</institution>, Guangdong,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Lijuan" sort="Zhou, Lijuan" uniqKey="Zhou L" first="Lijuan" last="Zhou">Lijuan Zhou</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wei, Hejiang" sort="Wei, Hejiang" uniqKey="Wei H" first="Hejiang" last="Wei">Hejiang Wei</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gao, Rongbao" sort="Gao, Rongbao" uniqKey="Gao R" first="Rongbao" last="Gao">Rongbao Gao</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Dayan" sort="Wang, Dayan" uniqKey="Wang D" first="Dayan" last="Wang">Dayan Wang</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shu, Yuelong" sort="Shu, Yuelong" uniqKey="Shu Y" first="Yuelong" last="Shu">Yuelong Shu</name><affiliation wicri:level="1"><nlm:aff id="AF1"><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF2"><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF3"><institution>School of Public Health (Shenzhen), Sun Yat-sen University</institution>, Guangdong,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Emerging Microbes & Infections</title><idno type="eISSN">2222-1751</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><p>It has recently been proposed that the Eurasian avian-like H1N1 (EA H1N1) swine influenza virus (SIV) is one of the most likely zoonotic viruses to cause the next influenza pandemic. Two main genotypes EA H1N1 viruses have been recognized to be infected humans in China. Our study finds that one of the genotypes JS1-like viruses are avirulent in mice. However, the other are HuN-like viruses and are virulent in mice. The molecular mechanism underlying this difference shows that the NP gene determines the virulence of the EA H1N1 viruses in mice. In addition, a single substitution, Q357K, in the NP protein of the EA H1N1 viruses alters the virulence phenotype. This substitution is a typical human signature marker, which is prevalent in human viruses but rarely detected in avian influenza viruses. The NP-Q357K substitution is readily to be occurred when avian influenza viruses circulate in pigs, and may facilitate their infection of humans and allow viruses also carrying NP-357K to circulate in humans. Our study demonstrates that the substitution Q357K in the NP protein plays a key role in the virulence phenotype of EA H1N1 SIVs, and provides important information for evaluating the pandemic risk of field influenza strains.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Castrucci, Mr" uniqKey="Castrucci M">MR Castrucci</name></author><author><name sortKey="Donatelli, I" uniqKey="Donatelli I">I Donatelli</name></author><author><name sortKey="Sidoli, L" uniqKey="Sidoli L">L Sidoli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, W" uniqKey="Ma W">W Ma</name></author><author><name sortKey="Kahn, Re" uniqKey="Kahn R">RE Kahn</name></author><author><name sortKey="Richt, Ja" uniqKey="Richt J">JA. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Emerg Microbes Infect</journal-id><journal-id journal-id-type="iso-abbrev">Emerg Microbes Infect</journal-id><journal-id journal-id-type="publisher-id">TEMI</journal-id><journal-id journal-id-type="publisher-id">temi20</journal-id><journal-title-group><journal-title>Emerging Microbes & Infections</journal-title></journal-title-group><issn pub-type="epub">2222-1751</issn><publisher><publisher-name>Taylor & Francis</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31267843</article-id><article-id pub-id-type="pmc">6609330</article-id><article-id pub-id-type="publisher-id">1635873</article-id><article-id pub-id-type="doi">10.1080/22221751.2019.1635873</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Mammalian-adaptive mutation NP-Q357K in Eurasian H1N1 Swine Influenza viruses determines the virulence phenotype in mice</article-title><alt-title alt-title-type="running-title">Emerging Microbes & Infections</alt-title><alt-title alt-title-type="running-authors">W. Zhu et al.</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhu</surname><given-names>Wenfei</given-names></name><xref ref-type="aff" rid="AF1"><sup>a</sup></xref><xref ref-type="aff" rid="AF2"><sup>b</sup></xref><xref ref-type="author-notes" rid="AN1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Feng</surname><given-names>Zhaomin</given-names></name><xref ref-type="aff" rid="AF1"><sup>a</sup></xref><xref ref-type="aff" rid="AF2"><sup>b</sup></xref><xref ref-type="author-notes" rid="AN1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Yongkun</given-names></name><xref ref-type="aff" rid="AF3"><sup>c</sup></xref><xref ref-type="author-notes" rid="AN1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Lei</given-names></name><xref ref-type="aff" rid="AF1"><sup>a</sup></xref><xref ref-type="aff" rid="AF2"><sup>b</sup></xref><xref ref-type="author-notes" rid="AN1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Jia</given-names></name><xref ref-type="aff" rid="AF1"><sup>a</sup></xref><xref ref-type="aff" rid="AF2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Xiyan</given-names></name><xref ref-type="aff" rid="AF1"><sup>a</sup></xref><xref ref-type="aff" rid="AF2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Suli</given-names></name><xref ref-type="aff" rid="AF3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhou</surname><given-names>Lijuan</given-names></name><xref ref-type="aff" rid="AF1"><sup>a</sup></xref><xref ref-type="aff" rid="AF2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wei</surname><given-names>Hejiang</given-names></name><xref ref-type="aff" rid="AF1"><sup>a</sup></xref><xref ref-type="aff" rid="AF2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gao</surname><given-names>Rongbao</given-names></name><xref ref-type="aff" rid="AF1"><sup>a</sup></xref><xref ref-type="aff" rid="AF2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Dayan</given-names></name><xref ref-type="aff" rid="AF1"><sup>a</sup></xref><xref ref-type="aff" rid="AF2"><sup>b</sup></xref><xref ref-type="corresp" rid="cor1"><sup>CONTACT</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shu</surname><given-names>Yuelong</given-names></name><xref ref-type="aff" rid="AF1"><sup>a</sup></xref><xref ref-type="aff" rid="AF2"><sup>b</sup></xref><xref ref-type="aff" rid="AF3"><sup>c</sup></xref><xref ref-type="corresp" rid="cor2"></xref></contrib><aff id="AF1"><label>a</label><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing,<country>People’s Republic of China</country></aff><aff id="AF2"><label>b</label><institution>Key Laboratory for Medical Virology, National Health and Family Planning Commission</institution>, Beijing,<country>People’s Republic of China</country></aff><aff id="AF3"><label>c</label><institution>School of Public Health (Shenzhen), Sun Yat-sen University</institution>, Guangdong,<country>People’s Republic of China</country></aff></contrib-group><author-notes><corresp id="cor1"><label>CONTACT</label> Dayan Wang <email xlink:href="dayanwang@cnic.org.cn">dayanwang@cnic.org.cn</email><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing102206, <country>People’s Republic of China</country></corresp><corresp id="cor2">Yuelong Shu <email xlink:href="shuylong@mail.sysu.edu.cn">shuylong@mail.sysu.edu.cn</email><institution>National Institute for Viral Disease Control and Prevention, Collaboration Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention</institution>, Beijing102206, <country>People’s Republic of China</country></corresp><fn id="AN1"><label>*</label><p>These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>03</day><month>7</month><year>2019</year></pub-date><volume>8</volume><issue>1</issue><fpage seq="96">989</fpage><lpage>999</lpage><history><date date-type="received"><day>14</day><month>4</month><year>2019</year></date><date date-type="rev-recd"><day>13</day><month>6</month><year>2019</year></date><date date-type="accepted"><day>16</day><month>6</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>The Author(s)</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="temi-8-1635873.pdf"></self-uri><abstract><title>ABSTRACT</title><p>It has recently been proposed that the Eurasian avian-like H1N1 (EA H1N1) swine influenza virus (SIV) is one of the most likely zoonotic viruses to cause the next influenza pandemic. Two main genotypes EA H1N1 viruses have been recognized to be infected humans in China. Our study finds that one of the genotypes JS1-like viruses are avirulent in mice. However, the other are HuN-like viruses and are virulent in mice. The molecular mechanism underlying this difference shows that the NP gene determines the virulence of the EA H1N1 viruses in mice. In addition, a single substitution, Q357K, in the NP protein of the EA H1N1 viruses alters the virulence phenotype. This substitution is a typical human signature marker, which is prevalent in human viruses but rarely detected in avian influenza viruses. The NP-Q357K substitution is readily to be occurred when avian influenza viruses circulate in pigs, and may facilitate their infection of humans and allow viruses also carrying NP-357K to circulate in humans. Our study demonstrates that the substitution Q357K in the NP protein plays a key role in the virulence phenotype of EA H1N1 SIVs, and provides important information for evaluating the pandemic risk of field influenza strains.</p></abstract><kwd-group kwd-group-type="author"><title>KEYWORDS</title><kwd>Eurasian avian-like H1N1 swine influenza viruses</kwd><kwd>NP gene</kwd><kwd>NP-K357Q</kwd><kwd>pathogenicity</kwd><kwd>pandemic potential</kwd></kwd-group><funding-group><award-group><funding-source><named-content content-type="funder-name">National Key R& D Program of China</named-content></funding-source><award-id>2016YFC1200200</award-id><award-id>2016YFD0500208</award-id></award-group><award-group><funding-source><named-content content-type="funder-name">National Science and Technology Major Project of the Ministry of Science and Technology of China</named-content></funding-source><award-id>2017ZX10304402-001-019</award-id></award-group><award-group><funding-source><named-content content-type="funder-name">National Natural Science Foundation of China</named-content><named-content content-type="funder-identifier">10.13039/501100001809</named-content></funding-source><award-id>81601758</award-id><award-id>81525017</award-id><award-id>31761133003</award-id></award-group><funding-statement>This study was supported by the National Natural Science Foundation of China (81601758 and to WFZ), National Key R&D Program of China (2016YFC1200200 to YLS and 2016YFD0500208 to DYW), National Natural Science Foundation of China (81525017 to YLS), National Natural Science Foundation of China (31761133003), and National Science and Technology Major Project of the Ministry of Science and Technology of China (2017ZX10304402-001-019 to RBG).</funding-statement></funding-group><counts><fig-count count="6"></fig-count><table-count count="1"></table-count><equation-count count="0"></equation-count><ref-count count="52"></ref-count><page-count count="11"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Zhu, Wenfei" sort="Zhu, Wenfei" uniqKey="Zhu W" first="Wenfei" last="Zhu">Wenfei Zhu</name></noRegion><name sortKey="Chen, Yongkun" sort="Chen, Yongkun" uniqKey="Chen Y" first="Yongkun" last="Chen">Yongkun Chen</name><name sortKey="Feng, Zhaomin" sort="Feng, Zhaomin" uniqKey="Feng Z" first="Zhaomin" last="Feng">Zhaomin Feng</name><name sortKey="Feng, Zhaomin" sort="Feng, Zhaomin" uniqKey="Feng Z" first="Zhaomin" last="Feng">Zhaomin Feng</name><name sortKey="Gao, Rongbao" sort="Gao, Rongbao" uniqKey="Gao R" first="Rongbao" last="Gao">Rongbao Gao</name><name sortKey="Gao, Rongbao" sort="Gao, Rongbao" uniqKey="Gao R" first="Rongbao" last="Gao">Rongbao Gao</name><name sortKey="Li, Xiyan" sort="Li, Xiyan" uniqKey="Li X" first="Xiyan" last="Li">Xiyan Li</name><name sortKey="Li, Xiyan" sort="Li, Xiyan" uniqKey="Li X" first="Xiyan" last="Li">Xiyan Li</name><name sortKey="Liu, Jia" sort="Liu, Jia" uniqKey="Liu J" first="Jia" last="Liu">Jia Liu</name><name sortKey="Liu, Jia" sort="Liu, Jia" uniqKey="Liu J" first="Jia" last="Liu">Jia Liu</name><name sortKey="Liu, Suli" sort="Liu, Suli" uniqKey="Liu S" first="Suli" last="Liu">Suli Liu</name><name sortKey="Shu, Yuelong" sort="Shu, Yuelong" uniqKey="Shu Y" first="Yuelong" last="Shu">Yuelong Shu</name><name sortKey="Shu, Yuelong" sort="Shu, Yuelong" uniqKey="Shu Y" first="Yuelong" last="Shu">Yuelong Shu</name><name sortKey="Shu, Yuelong" sort="Shu, Yuelong" uniqKey="Shu Y" first="Yuelong" last="Shu">Yuelong Shu</name><name sortKey="Wang, Dayan" sort="Wang, Dayan" uniqKey="Wang D" first="Dayan" last="Wang">Dayan Wang</name><name sortKey="Wang, Dayan" sort="Wang, Dayan" uniqKey="Wang D" first="Dayan" last="Wang">Dayan Wang</name><name sortKey="Wei, Hejiang" sort="Wei, Hejiang" uniqKey="Wei H" first="Hejiang" last="Wei">Hejiang Wei</name><name sortKey="Wei, Hejiang" sort="Wei, Hejiang" uniqKey="Wei H" first="Hejiang" last="Wei">Hejiang Wei</name><name sortKey="Yang, Lei" sort="Yang, Lei" uniqKey="Yang L" first="Lei" last="Yang">Lei Yang</name><name sortKey="Yang, Lei" sort="Yang, Lei" uniqKey="Yang L" first="Lei" last="Yang">Lei Yang</name><name sortKey="Zhou, Lijuan" sort="Zhou, Lijuan" uniqKey="Zhou L" first="Lijuan" last="Zhou">Lijuan Zhou</name><name sortKey="Zhou, Lijuan" sort="Zhou, Lijuan" uniqKey="Zhou L" first="Lijuan" last="Zhou">Lijuan Zhou</name><name sortKey="Zhu, Wenfei" sort="Zhu, Wenfei" uniqKey="Zhu W" first="Wenfei" last="Zhu">Wenfei Zhu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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