Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor Binding
Identifieur interne : 001042 ( PascalFrancis/Corpus ); précédent : 001041; suivant : 001043Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor Binding
Auteurs : Salin Chutinimitkul ; Sander Herfst ; John Steel ; Anice C. Lowen ; JIANQIANG YE ; Debby Van Riel ; Eefje J. A. Schrauwen ; Theo M. Bestebroer ; Björn Koel ; David F. Burke ; Kyle H. Sutherland-Cash ; Chris S. Whittleston ; Colin A. Russell ; David J. Wales ; Derek J. Smith ; Marcel Jonges ; Adam Meijer ; Marion Koopmans ; Guus F. Rimmelzwaan ; Thijs Kuiken ; Albert D. M. E. Osterhaus ; Adolfo Garcia-Sastre ; Daniel R. Perez ; Ron A. M. FouchierSource :
- Journal of virology [ 0022-538X ] ; 2010.
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- Pascal (Inist)
English descriptors
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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.
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| NO : | PASCAL 10-0511467 INIST |
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| ET : | Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor Binding |
| AU : | CHUTINIMITKUL (Salin); HERFST (Sander); STEEL (John); LOWEN (Anice C.); JIANQIANG YE; VAN RIEL (Debby); SCHRAUWEN (Eefje J. A.); BESTEBROER (Theo M.); KOEL (Björn); BURKE (David F.); SUTHERLAND-CASH (Kyle H.); WHITTLESTON (Chris S.); RUSSELL (Colin A.); WALES (David J.); SMITH (Derek J.); JONGES (Marcel); MEIJER (Adam); KOOPMANS (Marion); RIMMELZWAAN (Guus F.); KUIKEN (Thijs); OSTERHAUS (Albert D. M. E.); GARCIA-SASTRE (Adolfo); PEREZ (Daniel R.); FOUCHIER (Ron A. M.) |
| AF : | National Influenza Center and Department of Virology, Erasmus Medical Center/Rotterdam/Pays-Bas (1 aut., 2 aut., 6 aut., 7 aut., 8 aut., 9 aut., 15 aut., 19 aut., 20 aut., 21 aut., 24 aut.); Department of Microbiology, Mount Sinai School of Medicine/New York, New York/Etats-Unis (3 aut., 4 aut., 22 aut.); Department of Veterinary Medicine, University of Maryland/College Park, Maryland/Etats-Unis (5 aut., 23 aut.); Department of Zoology, University of Cambridge, Downing Street/Cambridge CB2 3EJ/Royaume-Uni (10 aut., 13 aut., 15 aut.); University Chemical Laboratories, University of Cambridge, Lensfield Road/Cambridge CB2 1EW/Royaume-Uni (11 aut., 12 aut., 14 aut.); National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven/Pays-Bas (16 aut., 17 aut., 18 aut.); Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine/New York, New York/Etats-Unis (22 aut.); Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine/New York, New York/Etats-Unis (22 aut.); Fogarty International Center, National Institutes of Health/Bethesda, Maryland/Etats-Unis (13 aut., 15 aut.) |
| DT : | Publication en série; Niveau analytique |
| SO : | Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2010; Vol. 84; No. 22; Pp. 11802-11813; Bibl. 56 ref. |
| LA : | Anglais |
| EA : | 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. |
| CC : | 002A05C10 |
| FD : | Virus grippal A; Virulence; Hémagglutinine |
| FG : | Influenzavirus A; Orthomyxoviridae; Virus |
| ED : | Influenza A virus; Virulence; Hemagglutinin |
| EG : | Influenzavirus A; Orthomyxoviridae; Virus |
| SD : | Influenza A virus; Virulencia; Hemoaglutinina |
| LO : | INIST-13592.354000191376530190 |
| ID : | 10-0511467 |
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Smith</name><affiliation><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></affiliation><affiliation><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></affiliation><affiliation><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></affiliation></author><author><name sortKey="Jonges, Marcel" sort="Jonges, Marcel" uniqKey="Jonges M" first="Marcel" last="Jonges">Marcel Jonges</name><affiliation><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></affiliation></author><author><name sortKey="Meijer, Adam" sort="Meijer, Adam" uniqKey="Meijer A" first="Adam" last="Meijer">Adam Meijer</name><affiliation><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></affiliation></author><author><name sortKey="Koopmans, Marion" sort="Koopmans, Marion" uniqKey="Koopmans M" first="Marion" last="Koopmans">Marion Koopmans</name><affiliation><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></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><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></affiliation></author><author><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name><affiliation><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></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><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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></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><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></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></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><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></affiliation></author><author><name sortKey="Herfst, Sander" sort="Herfst, Sander" uniqKey="Herfst S" first="Sander" last="Herfst">Sander Herfst</name><affiliation><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></affiliation></author><author><name sortKey="Steel, John" sort="Steel, John" uniqKey="Steel J" first="John" last="Steel">John Steel</name><affiliation><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></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><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></affiliation></author><author><name sortKey="Jianqiang Ye" sort="Jianqiang Ye" uniqKey="Jianqiang Ye" last="Jianqiang Ye">JIANQIANG YE</name><affiliation><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></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><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></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><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></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><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></affiliation></author><author><name sortKey="Koel, Bjorn" sort="Koel, Bjorn" uniqKey="Koel B" first="Björn" last="Koel">Björn Koel</name><affiliation><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></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><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></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><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></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><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></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><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></affiliation><affiliation><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></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><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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></affiliation></author><author><name sortKey="Jonges, Marcel" sort="Jonges, Marcel" uniqKey="Jonges M" first="Marcel" last="Jonges">Marcel Jonges</name><affiliation><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></affiliation></author><author><name sortKey="Meijer, Adam" sort="Meijer, Adam" uniqKey="Meijer A" first="Adam" last="Meijer">Adam Meijer</name><affiliation><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></affiliation></author><author><name sortKey="Koopmans, Marion" sort="Koopmans, Marion" uniqKey="Koopmans M" first="Marion" last="Koopmans">Marion Koopmans</name><affiliation><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></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><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></affiliation></author><author><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name><affiliation><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></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><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></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><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></affiliation><affiliation><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></affiliation><affiliation><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></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><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></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><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></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><server><NO>PASCAL 10-0511467 INIST</NO><ET>Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor Binding</ET><AU>CHUTINIMITKUL (Salin); HERFST (Sander); STEEL (John); LOWEN (Anice C.); JIANQIANG YE; VAN RIEL (Debby); SCHRAUWEN (Eefje J. A.); BESTEBROER (Theo M.); KOEL (Björn); BURKE (David F.); SUTHERLAND-CASH (Kyle H.); WHITTLESTON (Chris S.); RUSSELL (Colin A.); WALES (David J.); SMITH (Derek J.); JONGES (Marcel); MEIJER (Adam); KOOPMANS (Marion); RIMMELZWAAN (Guus F.); KUIKEN (Thijs); OSTERHAUS (Albert D. M. E.); GARCIA-SASTRE (Adolfo); PEREZ (Daniel R.); FOUCHIER (Ron A. M.)</AU><AF>National Influenza Center and Department of Virology, Erasmus Medical Center/Rotterdam/Pays-Bas (1 aut., 2 aut., 6 aut., 7 aut., 8 aut., 9 aut., 15 aut., 19 aut., 20 aut., 21 aut., 24 aut.); Department of Microbiology, Mount Sinai School of Medicine/New York, New York/Etats-Unis (3 aut., 4 aut., 22 aut.); Department of Veterinary Medicine, University of Maryland/College Park, Maryland/Etats-Unis (5 aut., 23 aut.); Department of Zoology, University of Cambridge, Downing Street/Cambridge CB2 3EJ/Royaume-Uni (10 aut., 13 aut., 15 aut.); University Chemical Laboratories, University of Cambridge, Lensfield Road/Cambridge CB2 1EW/Royaume-Uni (11 aut., 12 aut., 14 aut.); National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening Bilthoven/Pays-Bas (16 aut., 17 aut., 18 aut.); Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine/New York, New York/Etats-Unis (22 aut.); Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine/New York, New York/Etats-Unis (22 aut.); Fogarty International Center, National Institutes of Health/Bethesda, Maryland/Etats-Unis (13 aut., 15 aut.)</AF><DT>Publication en série; Niveau analytique</DT><SO>Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2010; Vol. 84; No. 22; Pp. 11802-11813; Bibl. 56 ref.</SO><LA>Anglais</LA><EA>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.</EA><CC>002A05C10</CC><FD>Virus grippal A; Virulence; Hémagglutinine</FD><FG>Influenzavirus A; Orthomyxoviridae; Virus</FG><ED>Influenza A virus; Virulence; Hemagglutinin</ED><EG>Influenzavirus A; Orthomyxoviridae; Virus</EG><SD>Influenza A virus; Virulencia; Hemoaglutinina</SD><LO>INIST-13592.354000191376530190</LO><ID>10-0511467</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
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