Structural and Functional Studies of Influenza Virus A/H6 Hemagglutinin
Identifieur interne : 000517 ( Main/Exploration ); précédent : 000516; suivant : 000518Structural and Functional Studies of Influenza Virus A/H6 Hemagglutinin
Auteurs : Fengyun Ni [États-Unis] ; Elena Kondrashkina [États-Unis] ; Qinghua Wang [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2015.
Abstract
In June 2013, the first human infection by avian influenza A(H6N1) virus was reported in Taiwan. This incident raised the concern for possible human epidemics and pandemics from H6 viruses. In this study, we performed structural and functional investigation on the hemagglutinin (HA) proteins of the human-infecting A/Taiwan/2/2013(H6N1) (TW H6) virus and an avian A/chicken/Guangdong/S1311/2010(H6N6) (GD H6) virus that transmitted efficiently in guinea pigs. Our results revealed that in the presence of HA1 Q226, the triad of HA1 S137, E190 and G228 in GD H6 HA allows the binding to both avian- and human-like receptors with a slight preference for avian receptors. Its conservation among the majority of H6 HAs provides an explanation for the broader host range of this subtype. Furthermore, the triad of N137, V190 and S228 in TW H6 HA may alleviate the requirement for a hydrophobic residue at HA1 226 of H2 and H3 HAs when binding to human-like receptors. Consequently, TW H6 HA has a slight preference for human receptors, thus may represent an intermediate towards a complete human adaptation. Importantly, the triad observed in TW H6 HA is detected in 74% H6 viruses isolated from Taiwan in the past 14 years, suggesting an elevated threat of H6 viruses from this region to human health. The novel roles of the triad at HA1 137, 190 and 228 of H6 HA in binding to receptors revealed here may also be used by other HA subtypes to achieve human adaptation, which needs to be further tested in laboratory and closely monitored in field surveillance.
Url:
DOI: 10.1371/journal.pone.0134576
PubMed: 26226046
PubMed Central: 4520562
Affiliations:
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Elena" uniqKey="Kondrashkina E" first="Elena" last="Kondrashkina">Elena Kondrashkina</name><affiliation wicri:level="2"><nlm:aff id="aff002"><addr-line>Life Sciences Collaborative Access Team (LS-CAT), Synchrotron Research Center, Northwestern University, Argonne, Illinois, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Life Sciences Collaborative Access Team (LS-CAT), Synchrotron Research Center, Northwestern University, Argonne, Illinois</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Wang, Qinghua" sort="Wang, Qinghua" uniqKey="Wang Q" first="Qinghua" last="Wang">Qinghua Wang</name><affiliation wicri:level="2"><nlm:aff id="aff001"><addr-line>Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>In June 2013, the first human infection by avian influenza A(H6N1) virus was reported in Taiwan. This incident raised the concern for possible human epidemics and pandemics from H6 viruses. In this study, we performed structural and functional investigation on the hemagglutinin (HA) proteins of the human-infecting A/Taiwan/2/2013(H6N1) (TW H6) virus and an avian A/chicken/Guangdong/S1311/2010(H6N6) (GD H6) virus that transmitted efficiently in guinea pigs. Our results revealed that in the presence of HA<sub>1</sub> Q226, the triad of HA<sub>1</sub> S137, E190 and G228 in GD H6 HA allows the binding to both avian- and human-like receptors with a slight preference for avian receptors. Its conservation among the majority of H6 HAs provides an explanation for the broader host range of this subtype. Furthermore, the triad of N137, V190 and S228 in TW H6 HA may alleviate the requirement for a hydrophobic residue at HA<sub>1</sub> 226 of H2 and H3 HAs when binding to human-like receptors. Consequently, TW H6 HA has a slight preference for human receptors, thus may represent an intermediate towards a complete human adaptation. Importantly, the triad observed in TW H6 HA is detected in 74% H6 viruses isolated from Taiwan in the past 14 years, suggesting an elevated threat of H6 viruses from this region to human health. The novel roles of the triad at HA<sub>1</sub> 137, 190 and 228 of H6 HA in binding to receptors revealed here may also be used by other HA subtypes to achieve human adaptation, which needs to be further tested in laboratory and closely monitored in field surveillance.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Gao, R" uniqKey="Gao R">R Gao</name></author><author><name sortKey="Cao, B" uniqKey="Cao B">B Cao</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name></author><author><name sortKey="Feng, Z" uniqKey="Feng Z">Z Feng</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, H" uniqKey="Chen H">H Chen</name></author><author><name sortKey="Yuan, H" uniqKey="Yuan H">H Yuan</name></author><author><name sortKey="Gao, R" uniqKey="Gao R">R Gao</name></author><author><name 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name="Texas"><name sortKey="Ni, Fengyun" sort="Ni, Fengyun" uniqKey="Ni F" first="Fengyun" last="Ni">Fengyun Ni</name></region><name sortKey="Kondrashkina, Elena" sort="Kondrashkina, Elena" uniqKey="Kondrashkina E" first="Elena" last="Kondrashkina">Elena Kondrashkina</name><name sortKey="Wang, Qinghua" sort="Wang, Qinghua" uniqKey="Wang Q" first="Qinghua" last="Wang">Qinghua Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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