Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus
Identifieur interne : 000A97 ( Pmc/Checkpoint ); précédent : 000A96; suivant : 000A98Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus
Auteurs : Claudia Pappas [États-Unis] ; Patricia V. Aguilar ; Christopher F. Basler ; Alicia Sol Rzano ; Hui Zeng [États-Unis] ; Lucy A. Perrone [États-Unis] ; Peter Palese ; Adolfo García-Sastre [États-Unis] ; Jacqueline M. Katz [États-Unis] ; Terrence M. Tumpey [États-Unis]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2008.
Abstract
The 1918 influenza pandemic was exceptionally severe, resulting in the death of up to 50 million people worldwide. Here, we show which virus genes contributed to the replication and virulence of the 1918 influenza virus. Recombinant viruses, in which genes of the 1918 virus were replaced with genes from a contemporary human H1N1 influenza virus, A/Texas/36/91 (Tx/91), were generated. The exchange of most 1918 influenza virus genes with seasonal influenza H1N1 virus genes did not alter the virulence of the 1918 virus; however, substitution of the hemagglutinin (HA), neuraminidase (NA), or polymerase subunit PB1 genes significantly affected the ability of this virus to cause severe disease in mice. The 1918 virus virulence observed in mice correlated with the ability of 1918 recombinant viruses to replicate efficiently in human airway cells. In a second series of experiments, eight 1918 1:7 recombinants were generated, in which each Tx/91 virus gene was individually replaced by a corresponding gene from 1918 virus. Replication capacity of the individual 1:7 reassortant viruses was assessed in mouse lungs and human airway cells. Increased virus titers were observed among 1:7 viruses containing individual 1918 HA, NA, and PB1 genes. In addition, the 1918 PB1:Tx/91 (1:7) virus showed a distinctly larger plaque size phenotype than the small plaque phenotype of the 1918 PA:Tx/91 and 1918 PB2:Tx/91 1:7 reassortants. These results highlight the importance of the 1918 HA, NA, and PB1 genes for optimal virus replication and virulence of this pandemic strain.
Url:
DOI: 10.1073/pnas.0711815105
PubMed: 18287069
PubMed Central: 2268585
Affiliations:
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PMC:2268585Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>The 1918 influenza pandemic was exceptionally severe, resulting in the death of up to 50 million people worldwide. Here, we show which virus genes contributed to the replication and virulence of the 1918 influenza virus. Recombinant viruses, in which genes of the 1918 virus were replaced with genes from a contemporary human H1N1 influenza virus, A/Texas/36/91 (Tx/91), were generated. The exchange of most 1918 influenza virus genes with seasonal influenza H1N1 virus genes did not alter the virulence of the 1918 virus; however, substitution of the hemagglutinin (HA), neuraminidase (NA), or polymerase subunit PB1 genes significantly affected the ability of this virus to cause severe disease in mice. The 1918 virus virulence observed in mice correlated with the ability of 1918 recombinant viruses to replicate efficiently in human airway cells. In a second series of experiments, eight 1918 1:7 recombinants were generated, in which each Tx/91 virus gene was individually replaced by a corresponding gene from 1918 virus. Replication capacity of the individual 1:7 reassortant viruses was assessed in mouse lungs and human airway cells. Increased virus titers were observed among 1:7 viruses containing individual 1918 HA, NA, and PB1 genes. In addition, the 1918 PB1:Tx/91 (1:7) virus showed a distinctly larger plaque size phenotype than the small plaque phenotype of the 1918 PA:Tx/91 and 1918 PB2:Tx/91 1:7 reassortants. These results highlight the importance of the 1918 HA, NA, and PB1 genes for optimal virus replication and virulence of this pandemic strain.</p>
</div>
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<title-group><article-title>Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Pappas</surname>
<given-names>Claudia</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
<xref ref-type="aff" rid="aff2"><sup>†</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Aguilar</surname>
<given-names>Patricia V.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>†</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Basler</surname>
<given-names>Christopher F.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>†</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Solórzano</surname>
<given-names>Alicia</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>†</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zeng</surname>
<given-names>Hui</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Perrone</surname>
<given-names>Lucy A.</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Palese</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>†</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>‡</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>§</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>García-Sastre</surname>
<given-names>Adolfo</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>†</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Katz</surname>
<given-names>Jacqueline M.</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tumpey</surname>
<given-names>Terrence M.</given-names>
</name>
<xref ref-type="aff" rid="aff1">*</xref>
<xref ref-type="corresp" rid="cor1"><sup>§</sup>
</xref>
</contrib>
<aff id="aff1">*Influenza Division, Mailstop G-16, National Center for Immunization and Respiratory Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road Northeast, Atlanta, GA 30333; and</aff>
<aff id="aff2">Departments of<sup>†</sup>
Microbiology and</aff>
<aff id="aff3"><sup>‡</sup>
Medicine and</aff>
<aff id="aff4"><sup>¶</sup>
Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029</aff>
</contrib-group>
<author-notes><corresp id="cor1"><sup>§</sup>
To whom correspondence may be addressed. E-mail: <email>peter.palese@mssm.edu</email>
or <email>tft9@cdc.gov</email>
</corresp>
<fn fn-type="con"><p>Contributed by Peter Palese, December 17, 2007</p>
</fn>
<fn fn-type="con"><p>Author contributions: C.P., C.F.B., H.Z., P.P., J.M.K., and T.M.T. designed research; C.P., H.Z., L.A.P., and T.M.T. performed research; C.P., P.V.A., C.F.B., A.S., P.P., and A.G.-S. contributed new reagents/analytic tools; C.P., C.F.B., and T.M.T. analyzed data; and C.P., H.Z., J.M.K., and T.M.T. wrote the paper.</p>
</fn>
<fn fn-type="conflict"><p>The authors declare no conflict of interest.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>26</day>
<month>2</month>
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<lpage>3069</lpage>
<history><date date-type="received"><day>4</day>
<month>12</month>
<year>2007</year>
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<permissions><copyright-statement>© 2008 by The National Academy of Sciences of the USA</copyright-statement>
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<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpq00808003064.pdf"></self-uri>
<abstract><p>The 1918 influenza pandemic was exceptionally severe, resulting in the death of up to 50 million people worldwide. Here, we show which virus genes contributed to the replication and virulence of the 1918 influenza virus. Recombinant viruses, in which genes of the 1918 virus were replaced with genes from a contemporary human H1N1 influenza virus, A/Texas/36/91 (Tx/91), were generated. The exchange of most 1918 influenza virus genes with seasonal influenza H1N1 virus genes did not alter the virulence of the 1918 virus; however, substitution of the hemagglutinin (HA), neuraminidase (NA), or polymerase subunit PB1 genes significantly affected the ability of this virus to cause severe disease in mice. The 1918 virus virulence observed in mice correlated with the ability of 1918 recombinant viruses to replicate efficiently in human airway cells. In a second series of experiments, eight 1918 1:7 recombinants were generated, in which each Tx/91 virus gene was individually replaced by a corresponding gene from 1918 virus. Replication capacity of the individual 1:7 reassortant viruses was assessed in mouse lungs and human airway cells. Increased virus titers were observed among 1:7 viruses containing individual 1918 HA, NA, and PB1 genes. In addition, the 1918 PB1:Tx/91 (1:7) virus showed a distinctly larger plaque size phenotype than the small plaque phenotype of the 1918 PA:Tx/91 and 1918 PB2:Tx/91 1:7 reassortants. These results highlight the importance of the 1918 HA, NA, and PB1 genes for optimal virus replication and virulence of this pandemic strain.</p>
</abstract>
<kwd-group><kwd>human airway cells</kwd>
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<tree><noCountry><name sortKey="Aguilar, Patricia V" sort="Aguilar, Patricia V" uniqKey="Aguilar P" first="Patricia V." last="Aguilar">Patricia V. Aguilar</name>
<name sortKey="Basler, Christopher F" sort="Basler, Christopher F" uniqKey="Basler C" first="Christopher F." last="Basler">Christopher F. Basler</name>
<name sortKey="Palese, Peter" sort="Palese, Peter" uniqKey="Palese P" first="Peter" last="Palese">Peter Palese</name>
<name sortKey="Sol Rzano, Alicia" sort="Sol Rzano, Alicia" uniqKey="Sol Rzano A" first="Alicia" last="Sol Rzano">Alicia Sol Rzano</name>
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<country name="États-Unis"><region name="Géorgie (États-Unis)"><name sortKey="Pappas, Claudia" sort="Pappas, Claudia" uniqKey="Pappas C" first="Claudia" last="Pappas">Claudia Pappas</name>
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<name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name>
<name sortKey="Katz, Jacqueline M" sort="Katz, Jacqueline M" uniqKey="Katz J" first="Jacqueline M." last="Katz">Jacqueline M. Katz</name>
<name sortKey="Perrone, Lucy A" sort="Perrone, Lucy A" uniqKey="Perrone L" first="Lucy A." last="Perrone">Lucy A. Perrone</name>
<name sortKey="Tumpey, Terrence M" sort="Tumpey, Terrence M" uniqKey="Tumpey T" first="Terrence M." last="Tumpey">Terrence M. Tumpey</name>
<name sortKey="Zeng, Hui" sort="Zeng, Hui" uniqKey="Zeng H" first="Hui" last="Zeng">Hui Zeng</name>
</country>
</tree>
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