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Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice

Identifieur interne : 000C18 ( Pmc/Curation ); précédent : 000C17; suivant : 000C19

Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice

Auteurs : Masato Hatta [États-Unis] ; Yasuko Hatta [États-Unis] ; Jin Hyun Kim [États-Unis] ; Shinji Watanabe [États-Unis] ; Kyoko Shinya [Japon] ; Tung Nguyen [Viêt Nam] ; Phuong Song Lien [Viêt Nam] ; Quynh Mai Le [Viêt Nam] ; Yoshihiro Kawaoka [États-Unis, Japon]

Source :

RBID : PMC:2000968

Abstract

Highly pathogenic avian H5N1 influenza A viruses have spread throughout Asia, Europe, and Africa, raising serious worldwide concern about their pandemic potential. Although more than 250 people have been infected with these viruses, with a consequent high rate of mortality, the molecular mechanisms responsible for the efficient transmission of H5N1 viruses among humans remain elusive. We used a mouse model to examine the role of the amino acid at position 627 of the PB2 viral protein in efficient replication of H5N1 viruses in the mammalian respiratory tract. Viruses possessing Lys at position 627 of PB2 replicated efficiently in lungs and nasal turbinates, as well as in cells, even at the lower temperature of 33 °C. Those viruses possessing Glu at this position replicated less well in nasal turbinates than in lungs, and less well in cells at the lower temperature. These results suggest that Lys at PB2–627 confers to avian H5N1 viruses the advantage of efficient growth in the upper and lower respiratory tracts of mammals. Therefore, efficient viral growth in the upper respiratory tract may provide a platform for the adaptation of avian H5N1 influenza viruses to humans and for efficient person-to-person virus transmission, in the context of changes in other viral properties including specificity for human (sialic acid α-2,6-galactose containing) receptors.


Url:
DOI: 10.1371/journal.ppat.0030133
PubMed: 17922570
PubMed Central: 2000968

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PMC:2000968

Le document en format XML

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<p>Highly pathogenic avian H5N1 influenza A viruses have spread throughout Asia, Europe, and Africa, raising serious worldwide concern about their pandemic potential. Although more than 250 people have been infected with these viruses, with a consequent high rate of mortality, the molecular mechanisms responsible for the efficient transmission of H5N1 viruses among humans remain elusive. We used a mouse model to examine the role of the amino acid at position 627 of the PB2 viral protein in efficient replication of H5N1 viruses in the mammalian respiratory tract. Viruses possessing Lys at position 627 of PB2 replicated efficiently in lungs and nasal turbinates, as well as in cells, even at the lower temperature of 33 °C. Those viruses possessing Glu at this position replicated less well in nasal turbinates than in lungs, and less well in cells at the lower temperature. These results suggest that Lys at PB2–627 confers to avian H5N1 viruses the advantage of efficient growth in the upper and lower respiratory tracts of mammals. Therefore, efficient viral growth in the upper respiratory tract may provide a platform for the adaptation of avian H5N1 influenza viruses to humans and for efficient person-to-person virus transmission, in the context of changes in other viral properties including specificity for human (sialic acid α-2,6-galactose containing) receptors.</p>
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<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">PLoS Pathog</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS Pathog</journal-id>
<journal-id journal-id-type="publisher-id">ppat</journal-id>
<journal-id journal-id-type="publisher-id">plpa</journal-id>
<journal-id journal-id-type="pmc">plospath</journal-id>
<journal-title-group>
<journal-title>PLoS Pathogens</journal-title>
</journal-title-group>
<issn pub-type="ppub">1553-7366</issn>
<issn pub-type="epub">1553-7374</issn>
<publisher>
<publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">17922570</article-id>
<article-id pub-id-type="pmc">2000968</article-id>
<article-id pub-id-type="doi">10.1371/journal.ppat.0030133</article-id>
<article-id pub-id-type="publisher-id">07-PLPA-RA-0307R2</article-id>
<article-id pub-id-type="sici">plpa-03-10-01</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline">
<subject>Virology</subject>
</subj-group>
<subj-group subj-group-type="System Taxonomy">
<subject>Viruses</subject>
<subject>Mus (mouse)</subject>
<subject>In Vitro</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice</article-title>
<alt-title alt-title-type="running-head">Influenza Virus in Respiratory Tract</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Hatta</surname>
<given-names>Masato</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Hatta</surname>
<given-names>Yasuko</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Jin Hyun</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Watanabe</surname>
<given-names>Shinji</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Shinya</surname>
<given-names>Kyoko</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nguyen</surname>
<given-names>Tung</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lien</surname>
<given-names>Phuong Song</given-names>
</name>
<xref ref-type="aff" rid="aff4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Le</surname>
<given-names>Quynh Mai</given-names>
</name>
<xref ref-type="aff" rid="aff5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kawaoka</surname>
<given-names>Yoshihiro</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff6">6</xref>
<xref ref-type="aff" rid="aff7">7</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>1</label>
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America</aff>
<aff id="aff2">
<label>2</label>
The Avian Zoonosis Research Centre, Tottori University, Tottori, Japan</aff>
<aff id="aff3">
<label>3</label>
National Centre for Veterinary Diagnostics, Hanoi, Vietnam</aff>
<aff id="aff4">
<label>4</label>
Vietnam Veterinary Association, Hanoi, Vietnam</aff>
<aff id="aff5">
<label>5</label>
National Institute of Hygiene and Epidemiology, Hanoi, Vietnam</aff>
<aff id="aff6">
<label>6</label>
Institute of Medical Science, University of Tokyo, Tokyo, Japan</aff>
<aff id="aff7">
<label>7</label>
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Holmes</surname>
<given-names>Edward C</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">The Pennsylvania State University, United States of America</aff>
<author-notes>
<corresp id="cor1">* To whom correspondence should be addressed. E-mail:
<email>kawaokay@svm.vetmed.wisc.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>10</month>
<year>2007</year>
</pub-date>
<pub-date pub-type="epub">
<day>5</day>
<month>10</month>
<year>2007</year>
</pub-date>
<volume>3</volume>
<issue>10</issue>
<elocation-id>e133</elocation-id>
<history>
<date date-type="received">
<day>17</day>
<month>5</month>
<year>2007</year>
</date>
<date date-type="accepted">
<day>26</day>
<month>7</month>
<year>2007</year>
</date>
</history>
<permissions>
<copyright-statement> © 2007 Hatta et al.</copyright-statement>
<copyright-year>2007</copyright-year>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p>
</license>
</permissions>
<abstract>
<p>Highly pathogenic avian H5N1 influenza A viruses have spread throughout Asia, Europe, and Africa, raising serious worldwide concern about their pandemic potential. Although more than 250 people have been infected with these viruses, with a consequent high rate of mortality, the molecular mechanisms responsible for the efficient transmission of H5N1 viruses among humans remain elusive. We used a mouse model to examine the role of the amino acid at position 627 of the PB2 viral protein in efficient replication of H5N1 viruses in the mammalian respiratory tract. Viruses possessing Lys at position 627 of PB2 replicated efficiently in lungs and nasal turbinates, as well as in cells, even at the lower temperature of 33 °C. Those viruses possessing Glu at this position replicated less well in nasal turbinates than in lungs, and less well in cells at the lower temperature. These results suggest that Lys at PB2–627 confers to avian H5N1 viruses the advantage of efficient growth in the upper and lower respiratory tracts of mammals. Therefore, efficient viral growth in the upper respiratory tract may provide a platform for the adaptation of avian H5N1 influenza viruses to humans and for efficient person-to-person virus transmission, in the context of changes in other viral properties including specificity for human (sialic acid α-2,6-galactose containing) receptors.</p>
</abstract>
<abstract abstract-type="summary">
<title>Author Summary</title>
<sec id="st1">
<title></title>
<p>Highly pathogenic avian H5N1 influenza A viruses have spread around the world since 2003, raising serious worldwide concern about their pandemic potential. Although efficient human-to-human transmission of this virus has not yet occurred, the potential of these viruses to acquire the ability is evident. The receptor specificity of the haemmaglutinin (HA) protein is considered a main factor affecting efficient transmission of H5N1 viruses. Yet, some H5N1 viruses isolated from humans that possess human receptor specificity have still failed to spread efficiently among humans. Therefore, amino acid substitutions in viral proteins other than the receptor-binding HA protein must be necessary for efficient growth and person-to-person transmission of avian H5N1 influenza virus. In our study, we defined the contribution of the amino acid at position 627 of the PB2 to efficient replication of H5N1 influenza viruses in the upper respiratory tracts of mice as a mammalian model. Because efficient viral growth in the upper respiratory tract of humans can facilitate virus excretion by coughing and sneezing, a mutation of PB2 amino acid 627, which contributes to efficient growth at this site in a mammal, may be prerequisite for efficient human-to-human transmission.</p>
</sec>
</abstract>
<counts>
<page-count count="6"></page-count>
</counts>
<custom-meta-group>
<custom-meta>
<meta-name>citation</meta-name>
<meta-value>Hatta M, Hatta Y, Kim JH, Watanabe S, Shinya K, et al. (2007) Growth of H5N1 influenza A viruses in the upper respiratory tracts of mice. PLoS Pathog 3(10): e133. doi:
<ext-link ext-link-type="doi" xlink:href="10.1371/journal.ppat.0030133">10.1371/journal.ppat.0030133</ext-link>
</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>

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