In Vitro Assessment of Attachment Pattern and Replication Efficiency of H5N1 Influenza A Viruses with Altered Receptor Specificity▿
Identifieur interne : 000519 ( Ncbi/Merge ); précédent : 000518; suivant : 000520In Vitro Assessment of Attachment Pattern and Replication Efficiency of H5N1 Influenza A Viruses with Altered Receptor Specificity▿
Auteurs : Salin Chutinimitkul [Pays-Bas] ; Debby Van Riel [Pays-Bas] ; Vincent J. Munster [Pays-Bas] ; Judith M. A. Van Den Brand [Pays-Bas] ; Guus F. Rimmelzwaan [Pays-Bas] ; Thijs Kuiken [Pays-Bas] ; Albert D. M. E. Osterhaus [Pays-Bas] ; Ron A. M. Fouchier [Pays-Bas] ; Emmie De Wit [Pays-Bas]Source :
- Journal of Virology [ 0022-538X ] ; 2010.
Abstract
The continuous circulation of the highly pathogenic avian influenza (HPAI) H5N1 virus has been a cause of great concern. The possibility of this virus acquiring specificity for the human influenza A virus receptor, α2,6-linked sialic acids (SA), and being able to transmit efficiently among humans is a constant threat to human health. Different studies have described amino acid substitutions in hemagglutinin (HA) of clinical HPAI H5N1 isolates or that were introduced experimentally that resulted in an increased, but not exclusive, binding of these virus strains to α2,6-linked SA. We introduced all previously described amino acid substitutions and combinations thereof into a single genetic background, influenza virus A/Indonesia/5/05 HA, and tested the receptor specificity of these 27 mutant viruses. The attachment pattern to ferret and human tissues of the upper and lower respiratory tract of viruses with α2,6-linked SA receptor preference was then determined and compared to the attachment pattern of a human influenza A virus (H3N2). At least three mutant viruses showed an attachment pattern to the human respiratory tract similar to that of the human H3N2 virus. Next, the replication efficiencies of these mutant viruses and the effects of three different neuraminidases on virus replication were determined. These data show that influenza virus A/Indonesia/5/05 potentially requires only a single amino acid substitution to acquire human receptor specificity, while at the same time remaining replication competent, thus suggesting that the pandemic threat posed by HPAI H5N1 is far from diminished.
Url:
DOI: 10.1128/JVI.02737-09
PubMed: 20392847
PubMed Central: 2903244
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PMC:2903244Le document en format XML
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Assessment of Attachment Pattern and Replication Efficiency of H5N1 Influenza A Viruses with Altered Receptor Specificity<xref ref-type="fn" rid="fn2">▿</xref>
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Assessment of Attachment Pattern and Replication Efficiency of H5N1 Influenza A Viruses with Altered Receptor Specificity<xref ref-type="fn" rid="fn2">▿</xref>
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<front><div type="abstract" xml:lang="en"><p>The continuous circulation of the highly pathogenic avian influenza (HPAI) H5N1 virus has been a cause of great concern. The possibility of this virus acquiring specificity for the human influenza A virus receptor, α2,6-linked sialic acids (SA), and being able to transmit efficiently among humans is a constant threat to human health. Different studies have described amino acid substitutions in hemagglutinin (HA) of clinical HPAI H5N1 isolates or that were introduced experimentally that resulted in an increased, but not exclusive, binding of these virus strains to α2,6-linked SA. We introduced all previously described amino acid substitutions and combinations thereof into a single genetic background, influenza virus A/Indonesia/5/05 HA, and tested the receptor specificity of these 27 mutant viruses. The attachment pattern to ferret and human tissues of the upper and lower respiratory tract of viruses with α2,6-linked SA receptor preference was then determined and compared to the attachment pattern of a human influenza A virus (H3N2). At least three mutant viruses showed an attachment pattern to the human respiratory tract similar to that of the human H3N2 virus. Next, the replication efficiencies of these mutant viruses and the effects of three different neuraminidases on virus replication were determined. These data show that influenza virus A/Indonesia/5/05 potentially requires only a single amino acid substitution to acquire human receptor specificity, while at the same time remaining replication competent, thus suggesting that the pandemic threat posed by HPAI H5N1 is far from diminished.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id>
<journal-id journal-id-type="publisher-id">jvirol</journal-id>
<journal-title-group><journal-title>Journal of Virology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher><publisher-name>American Society for Microbiology (ASM)</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">20392847</article-id>
<article-id pub-id-type="pmc">2903244</article-id>
<article-id pub-id-type="publisher-id">2737-09</article-id>
<article-id pub-id-type="doi">10.1128/JVI.02737-09</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject>
</subj-group>
</article-categories>
<title-group><article-title><italic>In Vitro</italic>
Assessment of Attachment Pattern and Replication Efficiency of H5N1 Influenza A Viruses with Altered Receptor Specificity<xref ref-type="fn" rid="fn2">▿</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Chutinimitkul</surname>
<given-names>Salin</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>van Riel</surname>
<given-names>Debby</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Munster</surname>
<given-names>Vincent J.</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
<xref ref-type="fn" rid="fn1">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van den Brand</surname>
<given-names>Judith M. A.</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rimmelzwaan</surname>
<given-names>Guus F.</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kuiken</surname>
<given-names>Thijs</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Osterhaus</surname>
<given-names>Albert D. M. E.</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fouchier</surname>
<given-names>Ron A. M.</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>de Wit</surname>
<given-names>Emmie</given-names>
</name>
<xref ref-type="aff" rid="aff0"></xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
</contrib-group>
<aff id="aff0">Department of Virology and National Influenza Center, Erasmus MC, P.O. Box 2040, 3000CA Rotterdam, Netherlands</aff>
<author-notes><corresp id="cor1"><label>*</label>
Corresponding author. Mailing address: Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840. Phone: (406) 375-7490. Fax: (406) 375-9620. E-mail: <email>emmie.dewit@nih.gov</email>
</corresp>
<fn id="fn1"><label>†</label>
<p>Present address: Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>7</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="epub"><day>14</day>
<month>4</month>
<year>2010</year>
</pub-date>
<volume>84</volume>
<issue>13</issue>
<fpage>6825</fpage>
<lpage>6833</lpage>
<history><date date-type="received"><day>30</day>
<month>12</month>
<year>2009</year>
</date>
<date date-type="accepted"><day>6</day>
<month>4</month>
<year>2010</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2010, American Society for Microbiology</copyright-statement>
<copyright-year>2010</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:href="zjv01310006825.pdf"></self-uri>
<abstract><p>The continuous circulation of the highly pathogenic avian influenza (HPAI) H5N1 virus has been a cause of great concern. The possibility of this virus acquiring specificity for the human influenza A virus receptor, α2,6-linked sialic acids (SA), and being able to transmit efficiently among humans is a constant threat to human health. Different studies have described amino acid substitutions in hemagglutinin (HA) of clinical HPAI H5N1 isolates or that were introduced experimentally that resulted in an increased, but not exclusive, binding of these virus strains to α2,6-linked SA. We introduced all previously described amino acid substitutions and combinations thereof into a single genetic background, influenza virus A/Indonesia/5/05 HA, and tested the receptor specificity of these 27 mutant viruses. The attachment pattern to ferret and human tissues of the upper and lower respiratory tract of viruses with α2,6-linked SA receptor preference was then determined and compared to the attachment pattern of a human influenza A virus (H3N2). At least three mutant viruses showed an attachment pattern to the human respiratory tract similar to that of the human H3N2 virus. Next, the replication efficiencies of these mutant viruses and the effects of three different neuraminidases on virus replication were determined. These data show that influenza virus A/Indonesia/5/05 potentially requires only a single amino acid substitution to acquire human receptor specificity, while at the same time remaining replication competent, thus suggesting that the pandemic threat posed by HPAI H5N1 is far from diminished.</p>
</abstract>
</article-meta>
</front>
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<name sortKey="De Wit, Emmie" sort="De Wit, Emmie" uniqKey="De Wit E" first="Emmie" last="De Wit">Emmie De Wit</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="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name>
<name sortKey="Munster, Vincent J" sort="Munster, Vincent J" uniqKey="Munster V" first="Vincent J." last="Munster">Vincent J. Munster</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="Van Den Brand, Judith M A" sort="Van Den Brand, Judith M A" uniqKey="Van Den Brand J" first="Judith M. A." last="Van Den Brand">Judith M. A. Van Den Brand</name>
<name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name>
</country>
</tree>
</affiliations>
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