Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor Binding
Identifieur interne : 000F04 ( PascalFrancis/Checkpoint ); précédent : 000F03; suivant : 000F05Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor Binding
Auteurs : Salin Chutinimitkul [Pays-Bas] ; Sander Herfst [Pays-Bas] ; John Steel [États-Unis] ; Anice C. Lowen [États-Unis] ; JIANQIANG YE [États-Unis] ; Debby Van Riel [Pays-Bas] ; Eefje J. A. Schrauwen [Pays-Bas] ; Theo M. Bestebroer [Pays-Bas] ; Björn Koel [Pays-Bas] ; David F. Burke [Royaume-Uni] ; Kyle H. Sutherland-Cash [Royaume-Uni] ; Chris S. Whittleston [Royaume-Uni] ; Colin A. Russell [Royaume-Uni, États-Unis] ; David J. Wales [Royaume-Uni] ; Derek J. Smith [Pays-Bas, Royaume-Uni, États-Unis] ; Marcel Jonges [Pays-Bas] ; Adam Meijer [Pays-Bas] ; Marion Koopmans [Pays-Bas] ; Guus F. Rimmelzwaan [Pays-Bas] ; Thijs Kuiken [Pays-Bas] ; Albert D. M. E. Osterhaus [Pays-Bas] ; Adolfo Garcia-Sastre [États-Unis] ; Daniel R. Perez [États-Unis] ; Ron A. M. Fouchier [Pays-Bas]Source :
- Journal of virology [ 0022-538X ] ; 2010.
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- Pascal (Inist)
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Abstract
The clinical impact of the 2009 pandemic influenza A(H1N1) virus (pdmH1N1) has been relatively low. However, amino acid substitution D222G in the hemagglutinin of pdmH1N1 has been associated with cases of severe disease and fatalities. D222G was introduced in a prototype pdmH1N1 by reverse genetics, and the effect on virus receptor binding, replication, antigenic properties, and pathogenesis and transmission in animal models was investigated. pdmH1N1 with D222G caused ocular disease in mice without further indications of enhanced virulence in mice and ferrets. pdmH1N1 with D222G retained transmissibility via aerosols or respiratory droplets in ferrets and guinea pigs. The virus displayed changes in attachment to human respiratory tissues in vitro, in particular increased binding to macrophages and type II pneumocytes in the alveoli and to tracheal and bronchial submucosal glands. Virus attachment studies further indicated that pdmH1N1 with D222G acquired dual receptor specificity for complex α2,3- and α2,6-linked sialic acids. Molecular dynamics modeling of the hemagglutinin structure provided an explanation for the retention of α2,6 binding. Altered receptor specificity of the virus with D222G thus affected interaction with cells of the human lower respiratory tract, possibly explaining the observed association with enhanced disease in humans.
Affiliations:
- Pays-Bas, Royaume-Uni, États-Unis
- Angleterre, Angleterre de l'Est, Hollande-Méridionale, Maryland, État de New York
- Cambridge, College Park (Maryland), Rotterdam
- Université de Cambridge, Université du Maryland
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Lowen</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Microbiology, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Jianqiang Ye" sort="Jianqiang Ye" uniqKey="Jianqiang Ye" last="Jianqiang Ye">JIANQIANG YE</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Veterinary Medicine, University of Maryland</s1><s2>College Park, Maryland</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Schrauwen, Eefje J A" sort="Schrauwen, Eefje J A" uniqKey="Schrauwen E" first="Eefje J. A." last="Schrauwen">Eefje J. A. Schrauwen</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Koel, Bjorn" sort="Koel, Bjorn" uniqKey="Koel B" first="Björn" last="Koel">Björn Koel</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Burke, David F" sort="Burke, David F" uniqKey="Burke D" first="David F." last="Burke">David F. Burke</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Zoology, University of Cambridge, Downing Street</s1><s2>Cambridge CB2 3EJ</s2><s3>GBR</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 3EJ</wicri:noRegion><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Sutherland Cash, Kyle H" sort="Sutherland Cash, Kyle H" uniqKey="Sutherland Cash K" first="Kyle H." last="Sutherland-Cash">Kyle H. Sutherland-Cash</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>University Chemical Laboratories, University of Cambridge, Lensfield Road</s1><s2>Cambridge CB2 1EW</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 1EW</wicri:noRegion></affiliation></author><author><name sortKey="Whittleston, Chris S" sort="Whittleston, Chris S" uniqKey="Whittleston C" first="Chris S." last="Whittleston">Chris S. Whittleston</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>University Chemical Laboratories, University of Cambridge, Lensfield Road</s1><s2>Cambridge CB2 1EW</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 1EW</wicri:noRegion></affiliation></author><author><name sortKey="Russell, Colin A" sort="Russell, Colin A" uniqKey="Russell C" first="Colin A." last="Russell">Colin A. Russell</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Zoology, University of Cambridge, Downing Street</s1><s2>Cambridge CB2 3EJ</s2><s3>GBR</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 3EJ</wicri:noRegion><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="09"><s1>Fogarty International Center, National Institutes of Health</s1><s2>Bethesda, Maryland</s2><s3>USA</s3><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Wales, David J" sort="Wales, David J" uniqKey="Wales D" first="David J." last="Wales">David J. Wales</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>University Chemical Laboratories, University of Cambridge, Lensfield Road</s1><s2>Cambridge CB2 1EW</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 1EW</wicri:noRegion></affiliation></author><author><name sortKey="Smith, Derek J" sort="Smith, Derek J" uniqKey="Smith D" first="Derek J." last="Smith">Derek J. Smith</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Zoology, University of Cambridge, Downing Street</s1><s2>Cambridge CB2 3EJ</s2><s3>GBR</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 3EJ</wicri:noRegion><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="09"><s1>Fogarty International Center, National Institutes of Health</s1><s2>Bethesda, Maryland</s2><s3>USA</s3><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Jonges, Marcel" sort="Jonges, Marcel" uniqKey="Jonges M" first="Marcel" last="Jonges">Marcel Jonges</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</s1><s3>NLD</s3><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</wicri:noRegion></affiliation></author><author><name sortKey="Meijer, Adam" sort="Meijer, Adam" uniqKey="Meijer A" first="Adam" last="Meijer">Adam Meijer</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</s1><s3>NLD</s3><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</wicri:noRegion></affiliation></author><author><name sortKey="Koopmans, Marion" sort="Koopmans, Marion" uniqKey="Koopmans M" first="Marion" last="Koopmans">Marion Koopmans</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</s1><s3>NLD</s3><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</wicri:noRegion></affiliation></author><author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="Garcia-Sastre">Adolfo Garcia-Sastre</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Microbiology, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="07"><s1>Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>22 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="08"><s1>Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>22 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Perez, Daniel R" sort="Perez, Daniel R" uniqKey="Perez D" first="Daniel R." last="Perez">Daniel R. Perez</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Veterinary Medicine, University of Maryland</s1><s2>College Park, Maryland</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">10-0511467</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 10-0511467 INIST</idno><idno type="RBID">Pascal:10-0511467</idno><idno type="wicri:Area/PascalFrancis/Corpus">001042</idno><idno type="wicri:Area/PascalFrancis/Curation">000E28</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000F04</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000F04</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor Binding</title><author><name sortKey="Chutinimitkul, Salin" sort="Chutinimitkul, Salin" uniqKey="Chutinimitkul S" first="Salin" last="Chutinimitkul">Salin Chutinimitkul</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Herfst, Sander" sort="Herfst, Sander" uniqKey="Herfst S" first="Sander" last="Herfst">Sander Herfst</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Steel, John" sort="Steel, John" uniqKey="Steel J" first="John" last="Steel">John Steel</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Microbiology, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Lowen, Anice C" sort="Lowen, Anice C" uniqKey="Lowen A" first="Anice C." last="Lowen">Anice C. Lowen</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Microbiology, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Jianqiang Ye" sort="Jianqiang Ye" uniqKey="Jianqiang Ye" last="Jianqiang Ye">JIANQIANG YE</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Veterinary Medicine, University of Maryland</s1><s2>College Park, Maryland</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Schrauwen, Eefje J A" sort="Schrauwen, Eefje J A" uniqKey="Schrauwen E" first="Eefje J. A." last="Schrauwen">Eefje J. A. Schrauwen</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Koel, Bjorn" sort="Koel, Bjorn" uniqKey="Koel B" first="Björn" last="Koel">Björn Koel</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Burke, David F" sort="Burke, David F" uniqKey="Burke D" first="David F." last="Burke">David F. Burke</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Zoology, University of Cambridge, Downing Street</s1><s2>Cambridge CB2 3EJ</s2><s3>GBR</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 3EJ</wicri:noRegion><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Sutherland Cash, Kyle H" sort="Sutherland Cash, Kyle H" uniqKey="Sutherland Cash K" first="Kyle H." last="Sutherland-Cash">Kyle H. Sutherland-Cash</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>University Chemical Laboratories, University of Cambridge, Lensfield Road</s1><s2>Cambridge CB2 1EW</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 1EW</wicri:noRegion></affiliation></author><author><name sortKey="Whittleston, Chris S" sort="Whittleston, Chris S" uniqKey="Whittleston C" first="Chris S." last="Whittleston">Chris S. Whittleston</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>University Chemical Laboratories, University of Cambridge, Lensfield Road</s1><s2>Cambridge CB2 1EW</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 1EW</wicri:noRegion></affiliation></author><author><name sortKey="Russell, Colin A" sort="Russell, Colin A" uniqKey="Russell C" first="Colin A." last="Russell">Colin A. Russell</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Zoology, University of Cambridge, Downing Street</s1><s2>Cambridge CB2 3EJ</s2><s3>GBR</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 3EJ</wicri:noRegion><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="09"><s1>Fogarty International Center, National Institutes of Health</s1><s2>Bethesda, Maryland</s2><s3>USA</s3><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Wales, David J" sort="Wales, David J" uniqKey="Wales D" first="David J." last="Wales">David J. Wales</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>University Chemical Laboratories, University of Cambridge, Lensfield Road</s1><s2>Cambridge CB2 1EW</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 1EW</wicri:noRegion></affiliation></author><author><name sortKey="Smith, Derek J" sort="Smith, Derek J" uniqKey="Smith D" first="Derek J." last="Smith">Derek J. Smith</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Zoology, University of Cambridge, Downing Street</s1><s2>Cambridge CB2 3EJ</s2><s3>GBR</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cambridge CB2 3EJ</wicri:noRegion><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="09"><s1>Fogarty International Center, National Institutes of Health</s1><s2>Bethesda, Maryland</s2><s3>USA</s3><sZ>13 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Jonges, Marcel" sort="Jonges, Marcel" uniqKey="Jonges M" first="Marcel" last="Jonges">Marcel Jonges</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</s1><s3>NLD</s3><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</wicri:noRegion></affiliation></author><author><name sortKey="Meijer, Adam" sort="Meijer, Adam" uniqKey="Meijer A" first="Adam" last="Meijer">Adam Meijer</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</s1><s3>NLD</s3><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</wicri:noRegion></affiliation></author><author><name sortKey="Koopmans, Marion" sort="Koopmans, Marion" uniqKey="Koopmans M" first="Marion" last="Koopmans">Marion Koopmans</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</s1><s3>NLD</s3><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</wicri:noRegion></affiliation></author><author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="Garcia-Sastre">Adolfo Garcia-Sastre</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Microbiology, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="07"><s1>Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>22 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="08"><s1>Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>22 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Perez, Daniel R" sort="Perez, Daniel R" uniqKey="Perez D" first="Daniel R." last="Perez">Daniel R. Perez</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Veterinary Medicine, University of Maryland</s1><s2>College Park, Maryland</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region><settlement type="city">College Park (Maryland)</settlement></placeName><orgName type="university">Université du Maryland</orgName></affiliation></author><author><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></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="2010">2010</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>Virulence</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Virus grippal A</term><term>Virulence</term><term>Hémagglutinine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The clinical impact of the 2009 pandemic influenza A(H1N1) virus (pdmH1N1) has been relatively low. However, amino acid substitution D222G in the hemagglutinin of pdmH1N1 has been associated with cases of severe disease and fatalities. D222G was introduced in a prototype pdmH1N1 by reverse genetics, and the effect on virus receptor binding, replication, antigenic properties, and pathogenesis and transmission in animal models was investigated. pdmH1N1 with D222G caused ocular disease in mice without further indications of enhanced virulence in mice and ferrets. pdmH1N1 with D222G retained transmissibility via aerosols or respiratory droplets in ferrets and guinea pigs. The virus displayed changes in attachment to human respiratory tissues in vitro, in particular increased binding to macrophages and type II pneumocytes in the alveoli and to tracheal and bronchial submucosal glands. Virus attachment studies further indicated that pdmH1N1 with D222G acquired dual receptor specificity for complex α2,3- and α2,6-linked sialic acids. Molecular dynamics modeling of the hemagglutinin structure provided an explanation for the retention of α2,6 binding. Altered receptor specificity of the virus with D222G thus affected interaction with cells of the human lower respiratory tract, possibly explaining the observed association with enhanced disease in humans.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0022-538X</s0></fA01><fA03 i2="1"><s0>J. virol.</s0></fA03><fA05><s2>84</s2></fA05><fA06><s2>22</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor Binding</s1></fA08><fA11 i1="01" i2="1"><s1>CHUTINIMITKUL (Salin)</s1></fA11><fA11 i1="02" i2="1"><s1>HERFST (Sander)</s1></fA11><fA11 i1="03" i2="1"><s1>STEEL (John)</s1></fA11><fA11 i1="04" i2="1"><s1>LOWEN (Anice C.)</s1></fA11><fA11 i1="05" i2="1"><s1>JIANQIANG YE</s1></fA11><fA11 i1="06" i2="1"><s1>VAN RIEL (Debby)</s1></fA11><fA11 i1="07" i2="1"><s1>SCHRAUWEN (Eefje J. A.)</s1></fA11><fA11 i1="08" i2="1"><s1>BESTEBROER (Theo M.)</s1></fA11><fA11 i1="09" i2="1"><s1>KOEL (Björn)</s1></fA11><fA11 i1="10" i2="1"><s1>BURKE (David F.)</s1></fA11><fA11 i1="11" i2="1"><s1>SUTHERLAND-CASH (Kyle H.)</s1></fA11><fA11 i1="12" i2="1"><s1>WHITTLESTON (Chris S.)</s1></fA11><fA11 i1="13" i2="1"><s1>RUSSELL (Colin A.)</s1></fA11><fA11 i1="14" i2="1"><s1>WALES (David J.)</s1></fA11><fA11 i1="15" i2="1"><s1>SMITH (Derek J.)</s1></fA11><fA11 i1="16" i2="1"><s1>JONGES (Marcel)</s1></fA11><fA11 i1="17" i2="1"><s1>MEIJER (Adam)</s1></fA11><fA11 i1="18" i2="1"><s1>KOOPMANS (Marion)</s1></fA11><fA11 i1="19" i2="1"><s1>RIMMELZWAAN (Guus F.)</s1></fA11><fA11 i1="20" i2="1"><s1>KUIKEN (Thijs)</s1></fA11><fA11 i1="21" i2="1"><s1>OSTERHAUS (Albert D. M. E.)</s1></fA11><fA11 i1="22" i2="1"><s1>GARCIA-SASTRE (Adolfo)</s1></fA11><fA11 i1="23" i2="1"><s1>PEREZ (Daniel R.)</s1></fA11><fA11 i1="24" i2="1"><s1>FOUCHIER (Ron A. M.)</s1></fA11><fA14 i1="01"><s1>National Influenza Center and Department of Virology, Erasmus Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>15 aut.</sZ><sZ>19 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ><sZ>24 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Microbiology, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>22 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Veterinary Medicine, University of Maryland</s1><s2>College Park, Maryland</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>23 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Zoology, University of Cambridge, Downing Street</s1><s2>Cambridge CB2 3EJ</s2><s3>GBR</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>15 aut.</sZ></fA14><fA14 i1="05"><s1>University Chemical Laboratories, University of Cambridge, Lensfield Road</s1><s2>Cambridge CB2 1EW</s2><s3>GBR</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>14 aut.</sZ></fA14><fA14 i1="06"><s1>National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven</s1><s3>NLD</s3><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ></fA14><fA14 i1="07"><s1>Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>22 aut.</sZ></fA14><fA14 i1="08"><s1>Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine</s1><s2>New York, New York</s2><s3>USA</s3><sZ>22 aut.</sZ></fA14><fA14 i1="09"><s1>Fogarty International Center, National Institutes of Health</s1><s2>Bethesda, Maryland</s2><s3>USA</s3><sZ>13 aut.</sZ><sZ>15 aut.</sZ></fA14><fA20><s1>11802-11813</s1></fA20><fA21><s1>2010</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>13592</s2><s5>354000191376530190</s5></fA43><fA44><s0>0000</s0><s1>© 2010 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>56 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>10-0511467</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Journal of virology</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>The clinical impact of the 2009 pandemic influenza A(H1N1) virus (pdmH1N1) has been relatively low. However, amino acid substitution D222G in the hemagglutinin of pdmH1N1 has been associated with cases of severe disease and fatalities. D222G was introduced in a prototype pdmH1N1 by reverse genetics, and the effect on virus receptor binding, replication, antigenic properties, and pathogenesis and transmission in animal models was investigated. pdmH1N1 with D222G caused ocular disease in mice without further indications of enhanced virulence in mice and ferrets. pdmH1N1 with D222G retained transmissibility via aerosols or respiratory droplets in ferrets and guinea pigs. The virus displayed changes in attachment to human respiratory tissues in vitro, in particular increased binding to macrophages and type II pneumocytes in the alveoli and to tracheal and bronchial submucosal glands. Virus attachment studies further indicated that pdmH1N1 with D222G acquired dual receptor specificity for complex α2,3- and α2,6-linked sialic acids. Molecular dynamics modeling of the hemagglutinin structure provided an explanation for the retention of α2,6 binding. Altered receptor specificity of the virus with D222G thus affected interaction with cells of the human lower respiratory tract, possibly explaining the observed association with enhanced disease in humans.</s0></fC01><fC02 i1="01" i2="X"><s0>002A05C10</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Virus grippal A</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Influenza A virus</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Influenza A virus</s0><s2>NW</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Virulence</s0><s5>05</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Virulence</s0><s5>05</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Virulencia</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Hémagglutinine</s0><s5>06</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Hemagglutinin</s0><s5>06</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Hemoaglutinina</s0><s5>06</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Influenzavirus A</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Influenzavirus A</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Influenzavirus A</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Virus</s0><s2>NW</s2></fC07><fN21><s1>347</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist><affiliations><list><country><li>Pays-Bas</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Angleterre de l'Est</li><li>Hollande-Méridionale</li><li>Maryland</li><li>État de New York</li></region><settlement><li>Cambridge</li><li>College Park (Maryland)</li><li>Rotterdam</li></settlement><orgName><li>Université de Cambridge</li><li>Université du Maryland</li></orgName></list><tree><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Chutinimitkul, Salin" sort="Chutinimitkul, Salin" uniqKey="Chutinimitkul S" first="Salin" last="Chutinimitkul">Salin Chutinimitkul</name></region><name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name><name sortKey="Herfst, Sander" sort="Herfst, Sander" uniqKey="Herfst S" first="Sander" last="Herfst">Sander Herfst</name><name sortKey="Jonges, Marcel" sort="Jonges, Marcel" uniqKey="Jonges M" first="Marcel" last="Jonges">Marcel Jonges</name><name sortKey="Koel, Bjorn" sort="Koel, Bjorn" uniqKey="Koel B" first="Björn" last="Koel">Björn Koel</name><name sortKey="Koopmans, Marion" sort="Koopmans, Marion" uniqKey="Koopmans M" first="Marion" last="Koopmans">Marion Koopmans</name><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name><name sortKey="Meijer, Adam" sort="Meijer, Adam" uniqKey="Meijer A" first="Adam" last="Meijer">Adam Meijer</name><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name><name sortKey="Schrauwen, Eefje J A" sort="Schrauwen, Eefje J A" uniqKey="Schrauwen E" first="Eefje J. A." last="Schrauwen">Eefje J. A. Schrauwen</name><name sortKey="Smith, Derek J" sort="Smith, Derek J" uniqKey="Smith D" first="Derek J." last="Smith">Derek J. Smith</name><name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name></country><country name="États-Unis"><region name="État de New York"><name sortKey="Steel, John" sort="Steel, John" uniqKey="Steel J" first="John" last="Steel">John Steel</name></region><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="Garcia-Sastre">Adolfo Garcia-Sastre</name><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="Garcia-Sastre">Adolfo Garcia-Sastre</name><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="Garcia-Sastre">Adolfo Garcia-Sastre</name><name sortKey="Jianqiang Ye" sort="Jianqiang Ye" uniqKey="Jianqiang Ye" last="Jianqiang Ye">JIANQIANG YE</name><name sortKey="Lowen, Anice C" sort="Lowen, Anice C" uniqKey="Lowen A" first="Anice C." last="Lowen">Anice C. Lowen</name><name sortKey="Perez, Daniel R" sort="Perez, Daniel R" uniqKey="Perez D" first="Daniel R." last="Perez">Daniel R. Perez</name><name sortKey="Russell, Colin A" sort="Russell, Colin A" uniqKey="Russell C" first="Colin A." last="Russell">Colin A. Russell</name><name sortKey="Smith, Derek J" sort="Smith, Derek J" uniqKey="Smith D" first="Derek J." last="Smith">Derek J. Smith</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Burke, David F" sort="Burke, David F" uniqKey="Burke D" first="David F." last="Burke">David F. Burke</name></region><name sortKey="Russell, Colin A" sort="Russell, Colin A" uniqKey="Russell C" first="Colin A." last="Russell">Colin A. Russell</name><name sortKey="Smith, Derek J" sort="Smith, Derek J" uniqKey="Smith D" first="Derek J." last="Smith">Derek J. Smith</name><name sortKey="Sutherland Cash, Kyle H" sort="Sutherland Cash, Kyle H" uniqKey="Sutherland Cash K" first="Kyle H." last="Sutherland-Cash">Kyle H. Sutherland-Cash</name><name sortKey="Wales, David J" sort="Wales, David J" uniqKey="Wales D" first="David J." last="Wales">David J. Wales</name><name sortKey="Whittleston, Chris S" sort="Whittleston, Chris S" uniqKey="Whittleston C" first="Chris S." last="Whittleston">Chris S. Whittleston</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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