Amino acid sequence analysis and identification of mutations under positive selection in hemagglutinin of 2009 influenza A (H1N1) isolates
Identifieur interne : 001393 ( Istex/Corpus ); précédent : 001392; suivant : 001394Amino acid sequence analysis and identification of mutations under positive selection in hemagglutinin of 2009 influenza A (H1N1) isolates
Auteurs : Xiaofan Ding ; Lifang Jiang ; Changwen Ke ; Zhan Yang ; Chunliang Lei ; Kaiyuan Cao ; Jun Xu ; Lin Xu ; Xingfen Yang ; Yonghui Zhang ; Ping Huang ; Weijun Huang ; Xun Zhu ; Zhenjian He ; Liping Liu ; Jun Li ; Jie Yuan ; Jueheng Wu ; Xiaoping Tang ; Mengfeng LiSource :
- Virus Genes [ 0920-8569 ] ; 2010-12-01.
English descriptors
Abstract
Abstract: The 2009 flu pandemic is caused by a new strain of influenza A (H1N1) virus, A/H1N1/09. With its high transmissibility, this novel virus has caused a pandemic and infected over 600,000 people globally. By comparing the hemaglutinin (HA) gene and protein sequences among over 700 A/H1N1/09 isolates, mutations in the receptor-binding sites and antigenic epitope regions were identified. Among these mutations, T220 and E/G239 were found to be strongly positively selected over the course of spreading of the A/H1N1/09 virus worldwide. Interestingly, both sites are located in the highly variable epitope regions of HA1, and residue 239 also plays an important role in the receptor-binding process. Further analyses demonstrated that the percentage of T220 mutants among all isolates increased rapidly during the evolution, and that an E/G239 mutation could decrease the binding affinity of the virus with its cellular receptor. Thus, due to a potential functional importance of residues 220 and 239, mutations at these sites, as well as the significant of positive selection on these sites deserves more attention, while new vaccines and therapeutic drugs are developed against this novel virus.
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DOI: 10.1007/s11262-010-0526-z
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China</mods:affiliation></affiliation></author><author><name sortKey="Xu, Lin" sort="Xu, Lin" uniqKey="Xu L" first="Lin" last="Xu">Lin Xu</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Yang, Xingfen" sort="Yang, Xingfen" uniqKey="Yang X" first="Xingfen" last="Yang">Xingfen Yang</name><affiliation><mods:affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Zhang, Yonghui" sort="Zhang, Yonghui" uniqKey="Zhang Y" first="Yonghui" last="Zhang">Yonghui Zhang</name><affiliation><mods:affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Huang, Ping" sort="Huang, Ping" uniqKey="Huang P" first="Ping" last="Huang">Ping Huang</name><affiliation><mods:affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Huang, Weijun" sort="Huang, Weijun" uniqKey="Huang W" first="Weijun" last="Huang">Weijun Huang</name><affiliation><mods:affiliation>Department of Medical Genetics and Center for Genome Research, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Zhu, Xun" sort="Zhu, Xun" uniqKey="Zhu X" first="Xun" last="Zhu">Xun Zhu</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="He, Zhenjian" sort="He, Zhenjian" uniqKey="He Z" first="Zhenjian" last="He">Zhenjian He</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="Liu, Liping" sort="Liu, Liping" uniqKey="Liu L" first="Liping" last="Liu">Liping Liu</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="Li, Jun" sort="Li, Jun" uniqKey="Li J" first="Jun" last="Li">Jun Li</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Yuan, Jie" sort="Yuan, Jie" uniqKey="Yuan J" first="Jie" last="Yuan">Jie Yuan</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Wu, Jueheng" sort="Wu, Jueheng" uniqKey="Wu J" first="Jueheng" last="Wu">Jueheng Wu</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="Tang, Xiaoping" sort="Tang, Xiaoping" uniqKey="Tang X" first="Xiaoping" last="Tang">Xiaoping Tang</name><affiliation><mods:affiliation>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: xtang@21cn.com</mods:affiliation></affiliation></author><author><name sortKey="Li, Mengfeng" sort="Li, Mengfeng" uniqKey="Li M" first="Mengfeng" last="Li">Mengfeng Li</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: limf@mail.sysu.edu.cn</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:E30A5250570A10A25DAEFF205FA4C70C8309B061</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1007/s11262-010-0526-z</idno><idno type="url">https://api.istex.fr/ark:/67375/VQC-0F66MVDD-P/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">001393</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001393</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Amino acid sequence analysis and identification of mutations under positive selection in hemagglutinin of 2009 influenza A (H1N1) isolates</title><author><name sortKey="Ding, Xiaofan" sort="Ding, Xiaofan" uniqKey="Ding X" first="Xiaofan" last="Ding">Xiaofan Ding</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="Jiang, Lifang" sort="Jiang, Lifang" uniqKey="Jiang L" first="Lifang" last="Jiang">Lifang Jiang</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="Ke, Changwen" sort="Ke, Changwen" uniqKey="Ke C" first="Changwen" last="Ke">Changwen Ke</name><affiliation><mods:affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Yang, Zhan" sort="Yang, Zhan" uniqKey="Yang Z" first="Zhan" last="Yang">Zhan Yang</name><affiliation><mods:affiliation>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="Lei, Chunliang" sort="Lei, Chunliang" uniqKey="Lei C" first="Chunliang" last="Lei">Chunliang Lei</name><affiliation><mods:affiliation>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="Cao, Kaiyuan" sort="Cao, Kaiyuan" uniqKey="Cao K" first="Kaiyuan" last="Cao">Kaiyuan Cao</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Research Centre for Clinical Laboratory Standard, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Xu, Jun" sort="Xu, Jun" uniqKey="Xu J" first="Jun" last="Xu">Jun Xu</name><affiliation><mods:affiliation>School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Xu, Lin" sort="Xu, Lin" uniqKey="Xu L" first="Lin" last="Xu">Lin Xu</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Yang, Xingfen" sort="Yang, Xingfen" uniqKey="Yang X" first="Xingfen" last="Yang">Xingfen Yang</name><affiliation><mods:affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Zhang, Yonghui" sort="Zhang, Yonghui" uniqKey="Zhang Y" first="Yonghui" last="Zhang">Yonghui Zhang</name><affiliation><mods:affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Huang, Ping" sort="Huang, Ping" uniqKey="Huang P" first="Ping" last="Huang">Ping Huang</name><affiliation><mods:affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Huang, Weijun" sort="Huang, Weijun" uniqKey="Huang W" first="Weijun" last="Huang">Weijun Huang</name><affiliation><mods:affiliation>Department of Medical Genetics and Center for Genome Research, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Zhu, Xun" sort="Zhu, Xun" uniqKey="Zhu X" first="Xun" last="Zhu">Xun Zhu</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="He, Zhenjian" sort="He, Zhenjian" uniqKey="He Z" first="Zhenjian" last="He">Zhenjian He</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="Liu, Liping" sort="Liu, Liping" uniqKey="Liu L" first="Liping" last="Liu">Liping Liu</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="Li, Jun" sort="Li, Jun" uniqKey="Li J" first="Jun" last="Li">Jun Li</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Yuan, Jie" sort="Yuan, Jie" uniqKey="Yuan J" first="Jie" last="Yuan">Jie Yuan</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation></author><author><name sortKey="Wu, Jueheng" sort="Wu, Jueheng" uniqKey="Wu J" first="Jueheng" last="Wu">Jueheng Wu</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation></author><author><name sortKey="Tang, Xiaoping" sort="Tang, Xiaoping" uniqKey="Tang X" first="Xiaoping" last="Tang">Xiaoping Tang</name><affiliation><mods:affiliation>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: xtang@21cn.com</mods:affiliation></affiliation></author><author><name sortKey="Li, Mengfeng" sort="Li, Mengfeng" uniqKey="Li M" first="Mengfeng" last="Li">Mengfeng Li</name><affiliation><mods:affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: limf@mail.sysu.edu.cn</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Virus Genes</title><title level="j" type="abbrev">Virus Genes</title><idno type="ISSN">0920-8569</idno><idno type="eISSN">1572-994X</idno><imprint><publisher>Springer US; http://www.springer-ny.com</publisher><pubPlace>Boston</pubPlace><date type="published" when="2010-12-01">2010-12-01</date><biblScope unit="volume">41</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="329">329</biblScope><biblScope unit="page" to="340">340</biblScope></imprint><idno type="ISSN">0920-8569</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0920-8569</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>H1N1 influenza virus</term><term>Hemaglutinin</term><term>Mutation</term><term>Positive selection</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The 2009 flu pandemic is caused by a new strain of influenza A (H1N1) virus, A/H1N1/09. With its high transmissibility, this novel virus has caused a pandemic and infected over 600,000 people globally. By comparing the hemaglutinin (HA) gene and protein sequences among over 700 A/H1N1/09 isolates, mutations in the receptor-binding sites and antigenic epitope regions were identified. Among these mutations, T220 and E/G239 were found to be strongly positively selected over the course of spreading of the A/H1N1/09 virus worldwide. Interestingly, both sites are located in the highly variable epitope regions of HA1, and residue 239 also plays an important role in the receptor-binding process. Further analyses demonstrated that the percentage of T220 mutants among all isolates increased rapidly during the evolution, and that an E/G239 mutation could decrease the binding affinity of the virus with its cellular receptor. Thus, due to a potential functional importance of residues 220 and 239, mutations at these sites, as well as the significant of positive selection on these sites deserves more attention, while new vaccines and therapeutic drugs are developed against this novel virus.</div></front></TEI><istex><corpusName>springer-journals</corpusName><author><json:item><name>Xiaofan Ding</name><affiliations><json:string>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</json:string><json:string>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</json:string></affiliations></json:item><json:item><name>Lifang Jiang</name><affiliations><json:string>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</json:string><json:string>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</json:string></affiliations></json:item><json:item><name>Changwen Ke</name><affiliations><json:string>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</json:string></affiliations></json:item><json:item><name>Zhan Yang</name><affiliations><json:string>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</json:string></affiliations></json:item><json:item><name>Chunliang Lei</name><affiliations><json:string>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</json:string></affiliations></json:item><json:item><name>Kaiyuan Cao</name><affiliations><json:string>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</json:string><json:string>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</json:string><json:string>Research Centre for Clinical Laboratory Standard, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</json:string></affiliations></json:item><json:item><name>Jun Xu</name><affiliations><json:string>School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China</json:string></affiliations></json:item><json:item><name>Lin Xu</name><affiliations><json:string>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</json:string><json:string>Department of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</json:string></affiliations></json:item><json:item><name>Xingfen Yang</name><affiliations><json:string>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</json:string></affiliations></json:item><json:item><name>Yonghui Zhang</name><affiliations><json:string>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</json:string></affiliations></json:item><json:item><name>Ping Huang</name><affiliations><json:string>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</json:string></affiliations></json:item><json:item><name>Weijun Huang</name><affiliations><json:string>Department of Medical Genetics and Center for Genome Research, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</json:string></affiliations></json:item><json:item><name>Xun Zhu</name><affiliations><json:string>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</json:string><json:string>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</json:string></affiliations></json:item><json:item><name>Zhenjian He</name><affiliations><json:string>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</json:string><json:string>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</json:string></affiliations></json:item><json:item><name>Liping Liu</name><affiliations><json:string>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</json:string><json:string>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</json:string></affiliations></json:item><json:item><name>Jun Li</name><affiliations><json:string>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</json:string><json:string>Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</json:string></affiliations></json:item><json:item><name>Jie Yuan</name><affiliations><json:string>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</json:string><json:string>Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</json:string></affiliations></json:item><json:item><name>Jueheng Wu</name><affiliations><json:string>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</json:string><json:string>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</json:string></affiliations></json:item><json:item><name>Xiaoping Tang</name><affiliations><json:string>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</json:string><json:string>E-mail: xtang@21cn.com</json:string></affiliations></json:item><json:item><name>Mengfeng Li</name><affiliations><json:string>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</json:string><json:string>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</json:string><json:string>E-mail: limf@mail.sysu.edu.cn</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>H1N1 influenza virus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Hemaglutinin</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Mutation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Positive selection</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>IAV : Influenza A virus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>WHO : World Health Organization</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HA : Hemagglutinin</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NP : Nucleoprotein</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NS : Nonstructural protein</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NA : Neuraminidase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>M : Matrix protein</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>CFR : Case fatality ratios</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>RBS : Receptor-binding sites</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PDB : Protein data bank</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>S : Serine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>T : Threonine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>D : Aspartic acid</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>G : Glycine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>E : Glutamic acid</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MOE : Molecular operating environment</value></json:item></subject><articleId><json:string>526</json:string><json:string>s11262-010-0526-z</json:string></articleId><arkIstex>ark:/67375/VQC-0F66MVDD-P</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>OriginalPaper</json:string></originalGenre><abstract>Abstract: The 2009 flu pandemic is caused by a new strain of influenza A (H1N1) virus, A/H1N1/09. With its high transmissibility, this novel virus has caused a pandemic and infected over 600,000 people globally. By comparing the hemaglutinin (HA) gene and protein sequences among over 700 A/H1N1/09 isolates, mutations in the receptor-binding sites and antigenic epitope regions were identified. Among these mutations, T220 and E/G239 were found to be strongly positively selected over the course of spreading of the A/H1N1/09 virus worldwide. Interestingly, both sites are located in the highly variable epitope regions of HA1, and residue 239 also plays an important role in the receptor-binding process. Further analyses demonstrated that the percentage of T220 mutants among all isolates increased rapidly during the evolution, and that an E/G239 mutation could decrease the binding affinity of the virus with its cellular receptor. Thus, due to a potential functional importance of residues 220 and 239, mutations at these sites, as well as the significant of positive selection on these sites deserves more attention, while new vaccines and therapeutic drugs are developed against this novel virus.</abstract><qualityIndicators><refBibsNative>false</refBibsNative><abstractWordCount>183</abstractWordCount><abstractCharCount>1204</abstractCharCount><keywordCount>20</keywordCount><score>9.196</score><pdfWordCount>5976</pdfWordCount><pdfCharCount>37944</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>12</pdfPageCount><pdfPageSize>595.276 x 790.866 pts</pdfPageSize></qualityIndicators><title>Amino acid sequence analysis and identification of mutations under positive selection in hemagglutinin of 2009 influenza A (H1N1) isolates</title><genre><json:string>research-article</json:string></genre><host><title>Virus Genes</title><language><json:string>unknown</json:string></language><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><issn><json:string>0920-8569</json:string></issn><eissn><json:string>1572-994X</json:string></eissn><journalId><json:string>11262</json:string></journalId><volume>41</volume><issue>3</issue><pages><first>329</first><last>340</last></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Plant Sciences</value></json:item><json:item><value>Virology</value></json:item><json:item><value>Medical Microbiology</value></json:item></subject></host><ark><json:string>ark:/67375/VQC-0F66MVDD-P</json:string></ark><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1007/s11262-010-0526-z</json:string></doi><id>E30A5250570A10A25DAEFF205FA4C70C8309B061</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-0F66MVDD-P/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-0F66MVDD-P/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/VQC-0F66MVDD-P/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Amino acid sequence analysis and identification of mutations under positive selection in hemagglutinin of 2009 influenza A (H1N1) isolates</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">Springer US; http://www.springer-ny.com</publisher><pubPlace>Boston</pubPlace><availability><licence><p>Springer Science+Business Media, LLC, 2010</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</p></availability><date>2010-03-04</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Amino acid sequence analysis and identification of mutations under positive selection in hemagglutinin of 2009 influenza A (H1N1) isolates</title><author xml:id="author-0000"><persName><forename type="first">Xiaofan</forename><surname>Ding</surname></persName><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Lifang</forename><surname>Jiang</surname></persName><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Changwen</forename><surname>Ke</surname></persName><affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Zhan</forename><surname>Yang</surname></persName><affiliation>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Chunliang</forename><surname>Lei</surname></persName><affiliation>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Kaiyuan</forename><surname>Cao</surname></persName><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation><affiliation>Research Centre for Clinical Laboratory Standard, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Jun</forename><surname>Xu</surname></persName><affiliation>School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China</affiliation></author><author xml:id="author-0007"><persName><forename type="first">Lin</forename><surname>Xu</surname></persName><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</affiliation></author><author xml:id="author-0008"><persName><forename type="first">Xingfen</forename><surname>Yang</surname></persName><affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</affiliation></author><author xml:id="author-0009"><persName><forename type="first">Yonghui</forename><surname>Zhang</surname></persName><affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</affiliation></author><author xml:id="author-0010"><persName><forename type="first">Ping</forename><surname>Huang</surname></persName><affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</affiliation></author><author xml:id="author-0011"><persName><forename type="first">Weijun</forename><surname>Huang</surname></persName><affiliation>Department of Medical Genetics and Center for Genome Research, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</affiliation></author><author xml:id="author-0012"><persName><forename type="first">Xun</forename><surname>Zhu</surname></persName><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation></author><author xml:id="author-0013"><persName><forename type="first">Zhenjian</forename><surname>He</surname></persName><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation></author><author xml:id="author-0014"><persName><forename type="first">Liping</forename><surname>Liu</surname></persName><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation></author><author xml:id="author-0015"><persName><forename type="first">Jun</forename><surname>Li</surname></persName><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</affiliation></author><author xml:id="author-0016"><persName><forename type="first">Jie</forename><surname>Yuan</surname></persName><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</affiliation></author><author xml:id="author-0017"><persName><forename type="first">Jueheng</forename><surname>Wu</surname></persName><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation></author><author xml:id="author-0018" corresp="yes"><persName><forename type="first">Xiaoping</forename><surname>Tang</surname></persName><email>xtang@21cn.com</email><affiliation>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</affiliation></author><author xml:id="author-0019" corresp="yes"><persName><forename type="first">Mengfeng</forename><surname>Li</surname></persName><email>limf@mail.sysu.edu.cn</email><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation></author><idno 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ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: The 2009 flu pandemic is caused by a new strain of influenza A (H1N1) virus, A/H1N1/09. With its high transmissibility, this novel virus has caused a pandemic and infected over 600,000 people globally. By comparing the hemaglutinin (HA) gene and protein sequences among over 700 A/H1N1/09 isolates, mutations in the receptor-binding sites and antigenic epitope regions were identified. Among these mutations, T220 and E/G239 were found to be strongly positively selected over the course of spreading of the A/H1N1/09 virus worldwide. Interestingly, both sites are located in the highly variable epitope regions of HA1, and residue 239 also plays an important role in the receptor-binding process. Further analyses demonstrated that the percentage of T220 mutants among all isolates increased rapidly during the evolution, and that an E/G239 mutation could decrease the binding affinity of the virus with its cellular receptor. Thus, due to a potential functional importance of residues 220 and 239, mutations at these sites, as well as the significant of positive selection on these sites deserves more attention, while new vaccines and therapeutic drugs are developed against this novel virus.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>H1N1 influenza virus</term></item><item><term>Hemaglutinin</term></item><item><term>Mutation</term></item><item><term>Positive selection</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>IAV</term><term>Influenza A virus</term></item><item><term>WHO</term><term>World Health Organization</term></item><item><term>HA</term><term>Hemagglutinin</term></item><item><term>NP</term><term>Nucleoprotein</term></item><item><term>NS</term><term>Nonstructural protein</term></item><item><term>NA</term><term>Neuraminidase</term></item><item><term>M</term><term>Matrix protein</term></item><item><term>CFR</term><term>Case fatality ratios</term></item><item><term>RBS</term><term>Receptor-binding sites</term></item><item><term>PDB</term><term>Protein data bank</term></item><item><term>S</term><term>Serine</term></item><item><term>T</term><term>Threonine</term></item><item><term>D</term><term>Aspartic acid</term></item><item><term>G</term><term>Glycine</term></item><item><term>E</term><term>Glutamic acid</term></item><item><term>MOE</term><term>Molecular operating environment</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Biomedicine</head><item><term>Plant Sciences</term></item><item><term>Virology</term></item><item><term>Medical Microbiology</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-03-04">Created</change><change 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isolates</ArticleTitle><ArticleFirstPage>329</ArticleFirstPage><ArticleLastPage>340</ArticleLastPage><ArticleHistory><RegistrationDate><Year>2010</Year><Month>8</Month><Day>17</Day></RegistrationDate><Received><Year>2010</Year><Month>3</Month><Day>4</Day></Received><Accepted><Year>2010</Year><Month>8</Month><Day>17</Day></Accepted><OnlineDate><Year>2010</Year><Month>8</Month><Day>31</Day></OnlineDate></ArticleHistory><ArticleCopyright><CopyrightHolderName>Springer Science+Business Media, LLC</CopyrightHolderName><CopyrightYear>2010</CopyrightYear></ArticleCopyright><ArticleGrants Type="Regular"><MetadataGrant Grant="OpenAccess"></MetadataGrant><AbstractGrant Grant="OpenAccess"></AbstractGrant><BodyPDFGrant Grant="Restricted"></BodyPDFGrant><BodyHTMLGrant Grant="Restricted"></BodyHTMLGrant><BibliographyGrant Grant="Restricted"></BibliographyGrant><ESMGrant Grant="Restricted"></ESMGrant></ArticleGrants></ArticleInfo><ArticleHeader><AuthorGroup><Author AffiliationIDS="Aff1 Aff2"><AuthorName DisplayOrder="Western"><GivenName>Xiaofan</GivenName><FamilyName>Ding</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff2"><AuthorName DisplayOrder="Western"><GivenName>Lifang</GivenName><FamilyName>Jiang</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff3"><AuthorName DisplayOrder="Western"><GivenName>Changwen</GivenName><FamilyName>Ke</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff4"><AuthorName DisplayOrder="Western"><GivenName>Zhan</GivenName><FamilyName>Yang</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff4"><AuthorName DisplayOrder="Western"><GivenName>Chunliang</GivenName><FamilyName>Lei</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff2 Aff5"><AuthorName DisplayOrder="Western"><GivenName>Kaiyuan</GivenName><FamilyName>Cao</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff6"><AuthorName DisplayOrder="Western"><GivenName>Jun</GivenName><FamilyName>Xu</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff7"><AuthorName DisplayOrder="Western"><GivenName>Lin</GivenName><FamilyName>Xu</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff3"><AuthorName DisplayOrder="Western"><GivenName>Xingfen</GivenName><FamilyName>Yang</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff3"><AuthorName DisplayOrder="Western"><GivenName>Yonghui</GivenName><FamilyName>Zhang</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff3"><AuthorName DisplayOrder="Western"><GivenName>Ping</GivenName><FamilyName>Huang</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff8"><AuthorName DisplayOrder="Western"><GivenName>Weijun</GivenName><FamilyName>Huang</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff2"><AuthorName DisplayOrder="Western"><GivenName>Xun</GivenName><FamilyName>Zhu</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff2"><AuthorName DisplayOrder="Western"><GivenName>Zhenjian</GivenName><FamilyName>He</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff2"><AuthorName DisplayOrder="Western"><GivenName>Liping</GivenName><FamilyName>Liu</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff9"><AuthorName DisplayOrder="Western"><GivenName>Jun</GivenName><FamilyName>Li</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff9"><AuthorName DisplayOrder="Western"><GivenName>Jie</GivenName><FamilyName>Yuan</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff2"><AuthorName DisplayOrder="Western"><GivenName>Jueheng</GivenName><FamilyName>Wu</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff4" CorrespondingAffiliationID="Aff4"><AuthorName DisplayOrder="Western"><GivenName>Xiaoping</GivenName><FamilyName>Tang</FamilyName></AuthorName><Contact><Phone>+86-20-83838688</Phone><Fax>+86-20-83838688</Fax><Email>xtang@21cn.com</Email></Contact></Author><Author AffiliationIDS="Aff1 Aff2" CorrespondingAffiliationID="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Mengfeng</GivenName><FamilyName>Li</FamilyName></AuthorName><Contact><Phone>+86-20-87332748</Phone><Fax>+86-20-87330209</Fax><Email>limf@mail.sysu.edu.cn</Email></Contact></Author><Affiliation ID="Aff1"><OrgDivision>Key Laboratory of Tropical Disease Control, Ministry of Education</OrgDivision><OrgName>Sun Yat-Sen University</OrgName><OrgAddress><City>Guangzhou</City><Country Code="CN">China</Country></OrgAddress></Affiliation><Affiliation ID="Aff2"><OrgDivision>Department of Microbiology, Zhongshan School of Medicine</OrgDivision><OrgName>Sun Yat-Sen University</OrgName><OrgAddress><Street>74 Zhongshan Road II</Street><City>Guangzhou</City><State>Guangdong</State><Postcode>510080</Postcode><Country Code="CN">China</Country></OrgAddress></Affiliation><Affiliation ID="Aff3"><OrgName>Guangdong Province Center for Disease Control and Prevention</OrgName><OrgAddress><City>Guangzhou</City><Country Code="CN">China</Country></OrgAddress></Affiliation><Affiliation ID="Aff4"><OrgName>The 8th People’s Hospital of Guangzhou</OrgName><OrgAddress><Street>627 Dongfengdong Road</Street><City>Guangzhou</City><State>Guangdong</State><Postcode>510060</Postcode><Country Code="CN">China</Country></OrgAddress></Affiliation><Affiliation ID="Aff5"><OrgDivision>Research Centre for Clinical Laboratory Standard, Zhongshan School of Medicine</OrgDivision><OrgName>Sun Yat-Sen University</OrgName><OrgAddress><City>Guangzhou</City><Country Code="CN">China</Country></OrgAddress></Affiliation><Affiliation ID="Aff6"><OrgDivision>School of Pharmaceutical Sciences</OrgDivision><OrgName>Sun Yat-Sen University</OrgName><OrgAddress><City>Guangzhou</City><Country Code="CN">China</Country></OrgAddress></Affiliation><Affiliation ID="Aff7"><OrgDivision>Department of Immunology, Zhongshan School of Medicine</OrgDivision><OrgName>Sun Yat-Sen University</OrgName><OrgAddress><City>Guangzhou</City><Country Code="CN">China</Country></OrgAddress></Affiliation><Affiliation ID="Aff8"><OrgDivision>Department of Medical Genetics and Center for Genome Research, Zhongshan School of Medicine</OrgDivision><OrgName>Sun Yat-Sen University</OrgName><OrgAddress><City>Guangzhou</City><Country Code="CN">China</Country></OrgAddress></Affiliation><Affiliation ID="Aff9"><OrgDivision>Department of Biochemistry, Zhongshan School of Medicine</OrgDivision><OrgName>Sun Yat-Sen University</OrgName><OrgAddress><City>Guangzhou</City><Country Code="CN">China</Country></OrgAddress></Affiliation></AuthorGroup><Abstract ID="Abs1" Language="En" OutputMedium="All"><Heading>Abstract</Heading><Para>The 2009 flu pandemic is caused by a new strain of influenza A (H1N1) virus, A/H1N1/09. With its high transmissibility, this novel virus has caused a pandemic and infected over 600,000 people globally. By comparing the hemaglutinin (HA) gene and protein sequences among over 700 A/H1N1/09 isolates, mutations in the receptor-binding sites and antigenic epitope regions were identified. Among these mutations, T220 and E/G239 were found to be strongly positively selected over the course of spreading of the A/H1N1/09 virus worldwide. Interestingly, both sites are located in the highly variable epitope regions of HA1, and residue 239 also plays an important role in the receptor-binding process. Further analyses demonstrated that the percentage of T220 mutants among all isolates increased rapidly during the evolution, and that an E/G239 mutation could decrease the binding affinity of the virus with its cellular receptor. Thus, due to a potential functional importance of residues 220 and 239, mutations at these sites, as well as the significant of positive selection on these sites deserves more attention, while new vaccines and therapeutic drugs are developed against this novel virus.</Para></Abstract><KeywordGroup Language="En" OutputMedium="All"><Heading>Keywords</Heading><Keyword>H1N1 influenza virus</Keyword><Keyword>Hemaglutinin</Keyword><Keyword>Mutation</Keyword><Keyword>Positive selection</Keyword></KeywordGroup><AbbreviationGroup><Heading>Abbreviations</Heading><DefinitionList><DefinitionListEntry><Term>IAV</Term><Description><Para>Influenza A virus</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>WHO</Term><Description><Para>World Health Organization</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>HA</Term><Description><Para>Hemagglutinin</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>NP</Term><Description><Para>Nucleoprotein</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>NS</Term><Description><Para>Nonstructural protein</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>NA</Term><Description><Para>Neuraminidase</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>M</Term><Description><Para>Matrix protein</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>CFR</Term><Description><Para>Case fatality ratios</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>RBS</Term><Description><Para>Receptor-binding sites</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>PDB</Term><Description><Para>Protein data bank</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>S</Term><Description><Para>Serine</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>T</Term><Description><Para>Threonine</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>D</Term><Description><Para>Aspartic acid</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>G</Term><Description><Para>Glycine</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>E</Term><Description><Para>Glutamic acid</Para></Description></DefinitionListEntry><DefinitionListEntry><Term>MOE</Term><Description><Para>Molecular operating environment</Para></Description></DefinitionListEntry></DefinitionList></AbbreviationGroup><ArticleNote Type="Misc"><SimplePara>Xiaofan Ding, Lifang Jiang, and Changwen Ke contributed equally to this study.</SimplePara></ArticleNote><ArticleNote Type="ESMHint"><Heading>Electronic supplementary material</Heading><SimplePara>The online version of this article (doi:<ExternalRef><RefSource>10.1007/s11262-010-0526-z</RefSource><RefTarget Address="10.1007/s11262-010-0526-z" TargetType="DOI"></RefTarget></ExternalRef>) contains supplementary material, which is available to authorized users.</SimplePara></ArticleNote></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Amino acid sequence analysis and identification of mutations under positive selection in hemagglutinin of 2009 influenza A (H1N1) isolates</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Amino acid sequence analysis and identification of mutations under positive selection in hemagglutinin of 2009 influenza A (H1N1) isolates</title></titleInfo><name type="personal"><namePart type="given">Xiaofan</namePart><namePart type="family">Ding</namePart><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lifang</namePart><namePart type="family">Jiang</namePart><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Changwen</namePart><namePart type="family">Ke</namePart><affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Zhan</namePart><namePart type="family">Yang</namePart><affiliation>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Chunliang</namePart><namePart type="family">Lei</namePart><affiliation>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kaiyuan</namePart><namePart type="family">Cao</namePart><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation><affiliation>Research Centre for Clinical Laboratory Standard, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jun</namePart><namePart type="family">Xu</namePart><affiliation>School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lin</namePart><namePart type="family">Xu</namePart><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Xingfen</namePart><namePart type="family">Yang</namePart><affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yonghui</namePart><namePart type="family">Zhang</namePart><affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ping</namePart><namePart type="family">Huang</namePart><affiliation>Guangdong Province Center for Disease Control and Prevention, Guangzhou, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Weijun</namePart><namePart type="family">Huang</namePart><affiliation>Department of Medical Genetics and Center for Genome Research, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Xun</namePart><namePart type="family">Zhu</namePart><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Zhenjian</namePart><namePart type="family">He</namePart><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Liping</namePart><namePart type="family">Liu</namePart><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jun</namePart><namePart type="family">Li</namePart><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jie</namePart><namePart type="family">Yuan</namePart><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jueheng</namePart><namePart type="family">Wu</namePart><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Xiaoping</namePart><namePart type="family">Tang</namePart><affiliation>The 8th People’s Hospital of Guangzhou, 627 Dongfengdong Road, 510060, Guangzhou, Guangdong, China</affiliation><affiliation>E-mail: xtang@21cn.com</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Mengfeng</namePart><namePart type="family">Li</namePart><affiliation>Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, Guangzhou, China</affiliation><affiliation>Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, 510080, Guangzhou, Guangdong, China</affiliation><affiliation>E-mail: limf@mail.sysu.edu.cn</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="OriginalPaper" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Springer US; http://www.springer-ny.com</publisher><place><placeTerm type="text">Boston</placeTerm></place><dateCreated encoding="w3cdtf">2010-03-04</dateCreated><dateIssued encoding="w3cdtf">2010-12-01</dateIssued><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract lang="en">Abstract: The 2009 flu pandemic is caused by a new strain of influenza A (H1N1) virus, A/H1N1/09. With its high transmissibility, this novel virus has caused a pandemic and infected over 600,000 people globally. By comparing the hemaglutinin (HA) gene and protein sequences among over 700 A/H1N1/09 isolates, mutations in the receptor-binding sites and antigenic epitope regions were identified. Among these mutations, T220 and E/G239 were found to be strongly positively selected over the course of spreading of the A/H1N1/09 virus worldwide. Interestingly, both sites are located in the highly variable epitope regions of HA1, and residue 239 also plays an important role in the receptor-binding process. Further analyses demonstrated that the percentage of T220 mutants among all isolates increased rapidly during the evolution, and that an E/G239 mutation could decrease the binding affinity of the virus with its cellular receptor. Thus, due to a potential functional importance of residues 220 and 239, mutations at these sites, as well as the significant of positive selection on these sites deserves more attention, while new vaccines and therapeutic drugs are developed against this novel virus.</abstract><subject lang="en"><genre>Keywords</genre><topic>H1N1 influenza virus</topic><topic>Hemaglutinin</topic><topic>Mutation</topic><topic>Positive selection</topic></subject><subject><genre>Abbreviations</genre><topic>IAV : Influenza A virus</topic><topic>WHO : World Health Organization</topic><topic>HA : Hemagglutinin</topic><topic>NP : Nucleoprotein</topic><topic>NS : Nonstructural protein</topic><topic>NA : Neuraminidase</topic><topic>M : Matrix protein</topic><topic>CFR : Case fatality ratios</topic><topic>RBS : Receptor-binding sites</topic><topic>PDB : Protein data bank</topic><topic>S : Serine</topic><topic>T : Threonine</topic><topic>D : Aspartic acid</topic><topic>G : Glycine</topic><topic>E : Glutamic acid</topic><topic>MOE : Molecular operating environment</topic></subject><relatedItem type="host"><titleInfo><title>Virus Genes</title></titleInfo><titleInfo type="abbreviated"><title>Virus Genes</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>Springer</publisher><dateIssued encoding="w3cdtf">2010-10-23</dateIssued><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><subject><genre>Biomedicine</genre><topic>Plant Sciences</topic><topic>Virology</topic><topic>Medical Microbiology</topic></subject><identifier type="ISSN">0920-8569</identifier><identifier type="eISSN">1572-994X</identifier><identifier type="JournalID">11262</identifier><identifier type="IssueArticleCount">19</identifier><identifier type="VolumeIssueCount">3</identifier><part><date>2010</date><detail type="volume"><number>41</number><caption>vol.</caption></detail><detail type="issue"><number>3</number><caption>no.</caption></detail><extent unit="pages"><start>329</start><end>340</end></extent></part><recordInfo><recordOrigin>Springer Science+Business Media, LLC, 2010</recordOrigin></recordInfo></relatedItem><identifier type="istex">E30A5250570A10A25DAEFF205FA4C70C8309B061</identifier><identifier type="ark">ark:/67375/VQC-0F66MVDD-P</identifier><identifier type="DOI">10.1007/s11262-010-0526-z</identifier><identifier type="ArticleID">526</identifier><identifier type="ArticleID">s11262-010-0526-z</identifier><accessCondition type="use and reproduction" contentType="copyright">Springer Science+Business Media, LLC, 2010</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</recordContentSource><recordOrigin>Springer Science+Business Media, LLC, 2010</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-0F66MVDD-P/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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