PandemieGrippaleV1, Main, Exploration, bibRecord, 002037

Key Molecular Factors in Hemagglutinin and PB2 Contribute to Efficient Transmission of the 2009 H1N1 Pandemic Influenza Virus

Identifieur interne : 002037 ( Main/Exploration ); précédent : 002036; suivant : 002038

Key Molecular Factors in Hemagglutinin and PB2 Contribute to Efficient Transmission of the 2009 H1N1 Pandemic Influenza Virus

Source :

Journal of virology [ 0022-538X ] ; 2012.

RBID : Pascal:12-0360835

Descripteurs français

Pascal (Inist)
- Virus grippal A, Hémagglutinine, Transmission.

English descriptors

KwdEn :
- Hemagglutinin, Influenza A virus, Transmission.

Abstract

Animal influenza viruses pose a clear threat to public health. Transmissibility among humans is a prerequisite for a novel influenza virus to cause a human pandemic. A novel reassortant swine influenza virus acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. However, the molecular aspects of influenza virus transmission remain poorly understood. Here, we show that an amino acid in hemagglutinin (HA) is important for the 2009 H1N1 influenza pandemic virus (2009/H 1N1 ) to bind to human virus receptors and confer respiratory droplet transmissibility in mammals. We found that the change from glutamine (Q) to arginine (R) at position 226 of HA, which causes a switch in receptor-binding preference from human α-2,6 to avian α-2,3 sialic acid, resulted in a virus incapable of respiratory droplet transmission in guinea pigs and reduced the virus's ability to replicate in the lungs of ferrets. The change from alanine (A) to threonine (T) at position 271 of PB2 also abolished the virus's respiratory droplet transmission in guinea pigs, and this mutation, together with the HA Q226R mutation, abolished the virus's respiratory droplet transmission in ferrets. Furthermore, we found that amino acid 271A of PB2 plays a key role in virus acquisition of the mutation at position 226 of HA that confers human receptor recognition. Our results highlight the importance of both the PB2 and HA genes on the adaptation and transmission of influenza viruses in humans and provide important insights for monitoring and evaluating the pandemic potential of field influenza viruses.

Affiliations:

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Le document en format XML

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<author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Key Molecular Factors in Hemagglutinin and PB2 Contribute to Efficient Transmission of the 2009 H1N1 Pandemic Influenza Virus</title>
<author><name sortKey="Ying Zhang" sort="Ying Zhang" uniqKey="Ying Zhang" last="Ying Zhang">YING ZHANG</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences</s1>
<s2>Harbin</s2>
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<author><name sortKey="Qianyi Zhang" sort="Qianyi Zhang" uniqKey="Qianyi Zhang" last="Qianyi Zhang">QIANYI ZHANG</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences</s1>
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<author><name sortKey="Yuwei Gao" sort="Yuwei Gao" uniqKey="Yuwei Gao" last="Yuwei Gao">YUWEI GAO</name>
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<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>The 11th Institute, Academy of Military Medical Sciences</s1>
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<author><name sortKey="Yuelong Shu" sort="Yuelong Shu" uniqKey="Yuelong Shu" last="Yuelong Shu">YUELONG SHU</name>
<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>National Institute for Viral Disease Control and Prevention, China CDC</s1>
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<placeName><settlement type="city">Pékin</settlement>
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<author><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name>
<affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Division of Virology, Department of Microbiology and Immunology; International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo</s1>
<s2>Tokyo</s2>
<s3>JPN</s3>
<sZ>10 aut.</sZ>
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<country>Japon</country>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
<orgName type="university">Université de Tokyo</orgName>
<placeName><settlement type="city">Madison (Wisconsin)</settlement>
<region type="state">Wisconsin</region>
</placeName>
<orgName type="university" n="3">Université du Wisconsin à Madison</orgName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison</s1>
<s2>Madison, Wisconsin</s2>
<s3>USA</s3>
<sZ>10 aut.</sZ>
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<country>États-Unis</country>
<placeName><region type="state">Wisconsin</region>
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<placeName><settlement type="city">Madison (Wisconsin)</settlement>
<region type="state">Wisconsin</region>
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<orgName type="university" n="3">Université du Wisconsin à Madison</orgName>
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<affiliation wicri:level="1"><inist:fA14 i1="07"><s1>ERATO Infection-Induced Host Responses Project</s1>
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<country>Japon</country>
<wicri:noRegion>ERATO Infection-Induced Host Responses Project</wicri:noRegion>
<placeName><settlement type="city">Tokyo</settlement>
<region type="province">Région de Kantō</region>
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</author>
<author><name sortKey="Zhigao Bu" sort="Zhigao Bu" uniqKey="Zhigao Bu" last="Zhigao Bu">ZHIGAO BU</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences</s1>
<s2>Harbin</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Harbin</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hualan Chen" sort="Hualan Chen" uniqKey="Hualan Chen" last="Hualan Chen">HUALAN CHEN</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences</s1>
<s2>Harbin</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Harbin</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>College of Veterinary Medicine, Gansu Agricultural University</s1>
<s2>Lanzhou</s2>
<s3>CHN</s3>
<sZ>2 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Lanzhou</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Hemagglutinin</term>
<term>Influenza A virus</term>
<term>Transmission</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Virus grippal A</term>
<term>Hémagglutinine</term>
<term>Transmission</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Animal influenza viruses pose a clear threat to public health. Transmissibility among humans is a prerequisite for a novel influenza virus to cause a human pandemic. A novel reassortant swine influenza virus acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. However, the molecular aspects of influenza virus transmission remain poorly understood. Here, we show that an amino acid in hemagglutinin (HA) is important for the 2009 H1N1 influenza pandemic virus (2009/H 1N1 ) to bind to human virus receptors and confer respiratory droplet transmissibility in mammals. We found that the change from glutamine (Q) to arginine (R) at position 226 of HA, which causes a switch in receptor-binding preference from human α-2,6 to avian α-2,3 sialic acid, resulted in a virus incapable of respiratory droplet transmission in guinea pigs and reduced the virus's ability to replicate in the lungs of ferrets. The change from alanine (A) to threonine (T) at position 271 of PB2 also abolished the virus's respiratory droplet transmission in guinea pigs, and this mutation, together with the HA Q226R mutation, abolished the virus's respiratory droplet transmission in ferrets. Furthermore, we found that amino acid 271A of PB2 plays a key role in virus acquisition of the mutation at position 226 of HA that confers human receptor recognition. Our results highlight the importance of both the PB2 and HA genes on the adaptation and transmission of influenza viruses in humans and provide important insights for monitoring and evaluating the pandemic potential of field influenza viruses.</div>
</front>
</TEI>
<affiliations><list><country><li>Japon</li>
<li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Dongbei</li>
<li>Jilin</li>
<li>Région de Kantō</li>
<li>Wisconsin</li>
</region>
<settlement><li>Changchun</li>
<li>Madison (Wisconsin)</li>
<li>Pékin</li>
<li>Tokyo</li>
</settlement>
<orgName><li>Université de Tokyo</li>
<li>Université du Wisconsin à Madison</li>
</orgName>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Ying Zhang" sort="Ying Zhang" uniqKey="Ying Zhang" last="Ying Zhang">YING ZHANG</name>
</noRegion>
<name sortKey="Hualan Chen" sort="Hualan Chen" uniqKey="Hualan Chen" last="Hualan Chen">HUALAN CHEN</name>
<name sortKey="Hualan Chen" sort="Hualan Chen" uniqKey="Hualan Chen" last="Hualan Chen">HUALAN CHEN</name>
<name sortKey="Huihui Kong" sort="Huihui Kong" uniqKey="Huihui Kong" last="Huihui Kong">HUIHUI KONG</name>
<name sortKey="Qianyi Zhang" sort="Qianyi Zhang" uniqKey="Qianyi Zhang" last="Qianyi Zhang">QIANYI ZHANG</name>
<name sortKey="Qianyi Zhang" sort="Qianyi Zhang" uniqKey="Qianyi Zhang" last="Qianyi Zhang">QIANYI ZHANG</name>
<name sortKey="Xianzhu Xia" sort="Xianzhu Xia" uniqKey="Xianzhu Xia" last="Xianzhu Xia">XIANZHU XIA</name>
<name sortKey="Xijun He" sort="Xijun He" uniqKey="Xijun He" last="Xijun He">XIJUN HE</name>
<name sortKey="Yongping Jiang" sort="Yongping Jiang" uniqKey="Yongping Jiang" last="Yongping Jiang">YONGPING JIANG</name>
<name sortKey="Yuelong Shu" sort="Yuelong Shu" uniqKey="Yuelong Shu" last="Yuelong Shu">YUELONG SHU</name>
<name sortKey="Yuntao Guan" sort="Yuntao Guan" uniqKey="Yuntao Guan" last="Yuntao Guan">YUNTAO GUAN</name>
<name sortKey="Yuwei Gao" sort="Yuwei Gao" uniqKey="Yuwei Gao" last="Yuwei Gao">YUWEI GAO</name>
<name sortKey="Zhigao Bu" sort="Zhigao Bu" uniqKey="Zhigao Bu" last="Zhigao Bu">ZHIGAO BU</name>
</country>
<country name="Japon"><region name="Région de Kantō"><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name>
</region>
<name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name>
</country>
<country name="États-Unis"><region name="Wisconsin"><name sortKey="Kawaoka, Yoshihiro" sort="Kawaoka, Yoshihiro" uniqKey="Kawaoka Y" first="Yoshihiro" last="Kawaoka">Yoshihiro Kawaoka</name>
</region>
</country>
</tree>
</affiliations>
</record>

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Key Molecular Factors in Hemagglutinin and PB2 Contribute to Efficient Transmission of the 2009 H1N1 Pandemic Influenza Virus

Key Molecular Factors in Hemagglutinin and PB2 Contribute to Efficient Transmission of the 2009 H1N1 Pandemic Influenza Virus

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