Comparative mutational analyses of influenza A viruses
Identifieur interne : 000768 ( Pmc/Corpus ); précédent : 000767; suivant : 000769Comparative mutational analyses of influenza A viruses
Auteurs : Peter Pak-Hang Cheung ; Igor B. Rogozin ; Ka-Tim Choy ; Hoi Yee Ng ; Joseph Sriyal Malik Peiris ; Hui-Ling YenSource :
- RNA [ 1355-8382 ] ; 2015.
Abstract
The error-prone RNA-dependent RNA polymerase (RdRP) and external selective pressures are the driving forces for RNA viral diversity. When confounded by selective pressures, it is difficult to assess if influenza A viruses (IAV) that have a wide host range possess comparable or distinct spontaneous mutational frequency in their RdRPs. We used in-depth bioinformatics analyses to assess the spontaneous mutational frequencies of two RdRPs derived from human seasonal (A/Wuhan/359/95; Wuhan) and H5N1 (A/Vietnam/1203/04; VN1203) viruses using the mini-genome system with a common firefly luciferase reporter serving as the template. High-fidelity reverse transcriptase was applied to generate high-quality mutational spectra which allowed us to assess and compare the mutational frequencies and mutable motifs along a target sequence of the two RdRPs of two different subtypes. We observed correlated mutational spectra (τ correlation
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DOI: 10.1261/rna.045369.114
PubMed: 25404565
PubMed Central: 4274636
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PMC:4274636Le document en format XML
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<author><name sortKey="Cheung, Peter Pak Hang" sort="Cheung, Peter Pak Hang" uniqKey="Cheung P" first="Peter Pak-Hang" last="Cheung">Peter Pak-Hang Cheung</name>
<affiliation><nlm:aff id="af1">School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong</nlm:aff>
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<author><name sortKey="Rogozin, Igor B" sort="Rogozin, Igor B" uniqKey="Rogozin I" first="Igor B." last="Rogozin">Igor B. Rogozin</name>
<affiliation><nlm:aff id="af2">National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894-6075, USA</nlm:aff>
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<author><name sortKey="Choy, Ka Tim" sort="Choy, Ka Tim" uniqKey="Choy K" first="Ka-Tim" last="Choy">Ka-Tim Choy</name>
<affiliation><nlm:aff id="af1">School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong</nlm:aff>
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<author><name sortKey="Ng, Hoi Yee" sort="Ng, Hoi Yee" uniqKey="Ng H" first="Hoi Yee" last="Ng">Hoi Yee Ng</name>
<affiliation><nlm:aff id="af1">School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong</nlm:aff>
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<author><name sortKey="Peiris, Joseph Sriyal Malik" sort="Peiris, Joseph Sriyal Malik" uniqKey="Peiris J" first="Joseph Sriyal Malik" last="Peiris">Joseph Sriyal Malik Peiris</name>
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<author><name sortKey="Yen, Hui Ling" sort="Yen, Hui Ling" uniqKey="Yen H" first="Hui-Ling" last="Yen">Hui-Ling Yen</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Comparative mutational analyses of influenza A viruses</title>
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<author><name sortKey="Choy, Ka Tim" sort="Choy, Ka Tim" uniqKey="Choy K" first="Ka-Tim" last="Choy">Ka-Tim Choy</name>
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<author><name sortKey="Ng, Hoi Yee" sort="Ng, Hoi Yee" uniqKey="Ng H" first="Hoi Yee" last="Ng">Hoi Yee Ng</name>
<affiliation><nlm:aff id="af1">School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong</nlm:aff>
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<author><name sortKey="Peiris, Joseph Sriyal Malik" sort="Peiris, Joseph Sriyal Malik" uniqKey="Peiris J" first="Joseph Sriyal Malik" last="Peiris">Joseph Sriyal Malik Peiris</name>
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<author><name sortKey="Yen, Hui Ling" sort="Yen, Hui Ling" uniqKey="Yen H" first="Hui-Ling" last="Yen">Hui-Ling Yen</name>
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<series><title level="j">RNA</title>
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<front><div type="abstract" xml:lang="en"><p>The error-prone RNA-dependent RNA polymerase (RdRP) and external selective pressures are the driving forces for RNA viral diversity. When confounded by selective pressures, it is difficult to assess if influenza A viruses (IAV) that have a wide host range possess comparable or distinct spontaneous mutational frequency in their RdRPs. We used in-depth bioinformatics analyses to assess the spontaneous mutational frequencies of two RdRPs derived from human seasonal (A/Wuhan/359/95; Wuhan) and H5N1 (A/Vietnam/1203/04; VN1203) viruses using the mini-genome system with a common firefly luciferase reporter serving as the template. High-fidelity reverse transcriptase was applied to generate high-quality mutational spectra which allowed us to assess and compare the mutational frequencies and mutable motifs along a target sequence of the two RdRPs of two different subtypes. We observed correlated mutational spectra (τ correlation <italic>P</italic>
< 0.0001), comparable mutational frequencies (H3N2:5.8 ± 0.9; H5N1:6.0 ± 0.5), and discovered a highly mutable motif “(A)AAG” for both Wuhan and VN1203 RdRPs. Results were then confirmed with two recombinant A/Puerto Rico/8/34 (PR8) viruses that possess RdRP derived from Wuhan or VN1203 (RG-PR8×Wuhan<sup>PB2, PB1, PA, NP</sup>
and RG-PR8×VN1203<sup>PB2, PB1, PA, NP</sup>
). Applying novel bioinformatics analysis on influenza mutational spectra, we provide a platform for a comprehensive analysis of the spontaneous mutation spectra for an RNA virus.</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">RNA</journal-id>
<journal-id journal-id-type="iso-abbrev">RNA</journal-id>
<journal-id journal-id-type="publisher-id">RNA</journal-id>
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<issn pub-type="ppub">1355-8382</issn>
<issn pub-type="epub">1469-9001</issn>
<publisher><publisher-name>Cold Spring Harbor Laboratory Press</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25404565</article-id>
<article-id pub-id-type="pmc">4274636</article-id>
<article-id pub-id-type="medline">9509184</article-id>
<article-id pub-id-type="publisher-id">RA</article-id>
<article-id pub-id-type="doi">10.1261/rna.045369.114</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Articles</subject>
</subj-group>
</article-categories>
<title-group><article-title>Comparative mutational analyses of influenza A viruses</article-title>
<alt-title alt-title-type="left-running">Cheung et al.</alt-title>
<alt-title alt-title-type="right-running">Influenza A virus mutational analysis</alt-title>
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<contrib-group><contrib contrib-type="author"><name><surname>Cheung</surname>
<given-names>Peter Pak-Hang</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
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<contrib contrib-type="author"><name><surname>Rogozin</surname>
<given-names>Igor B.</given-names>
</name>
<xref ref-type="aff" rid="af2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Choy</surname>
<given-names>Ka-Tim</given-names>
</name>
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</contrib>
<contrib contrib-type="author"><name><surname>Ng</surname>
<given-names>Hoi Yee</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Peiris</surname>
<given-names>Joseph Sriyal Malik</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Yen</surname>
<given-names>Hui-Ling</given-names>
</name>
<xref ref-type="aff" rid="af1">1</xref>
</contrib>
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<aff id="af1"><label>1</label>
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong</aff>
<aff id="af2"><label>2</label>
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894-6075, USA</aff>
<author-notes><corresp>Corresponding authors: <email>hyen@hku.hk</email>
, <email>malik@hkucc.hku.hk</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>1</month>
<year>2015</year>
</pub-date>
<volume>21</volume>
<issue>1</issue>
<fpage>36</fpage>
<lpage>47</lpage>
<history><date date-type="received"><day>19</day>
<month>3</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>1</day>
<month>10</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement><ext-link ext-link-type="uri" xlink:href="http://www.rnajournal.org/site/misc/terms.xhtml">© 2014 Cheung et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society</ext-link>
</copyright-statement>
<copyright-year>2014</copyright-year>
<license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/"><license-p>This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see <ext-link ext-link-type="uri" xlink:href="http://rnajournal.cshlp.org/site/misc/terms.xhtml">http://rnajournal.cshlp.org/site/misc/terms.xhtml</ext-link>
). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>
.</license-p>
</license>
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<self-uri content-type="pdf" xlink:href="36.pdf"></self-uri>
<abstract><p>The error-prone RNA-dependent RNA polymerase (RdRP) and external selective pressures are the driving forces for RNA viral diversity. When confounded by selective pressures, it is difficult to assess if influenza A viruses (IAV) that have a wide host range possess comparable or distinct spontaneous mutational frequency in their RdRPs. We used in-depth bioinformatics analyses to assess the spontaneous mutational frequencies of two RdRPs derived from human seasonal (A/Wuhan/359/95; Wuhan) and H5N1 (A/Vietnam/1203/04; VN1203) viruses using the mini-genome system with a common firefly luciferase reporter serving as the template. High-fidelity reverse transcriptase was applied to generate high-quality mutational spectra which allowed us to assess and compare the mutational frequencies and mutable motifs along a target sequence of the two RdRPs of two different subtypes. We observed correlated mutational spectra (τ correlation <italic>P</italic>
< 0.0001), comparable mutational frequencies (H3N2:5.8 ± 0.9; H5N1:6.0 ± 0.5), and discovered a highly mutable motif “(A)AAG” for both Wuhan and VN1203 RdRPs. Results were then confirmed with two recombinant A/Puerto Rico/8/34 (PR8) viruses that possess RdRP derived from Wuhan or VN1203 (RG-PR8×Wuhan<sup>PB2, PB1, PA, NP</sup>
and RG-PR8×VN1203<sup>PB2, PB1, PA, NP</sup>
). Applying novel bioinformatics analysis on influenza mutational spectra, we provide a platform for a comprehensive analysis of the spontaneous mutation spectra for an RNA virus.</p>
</abstract>
<kwd-group><kwd>H5N1</kwd>
<kwd>bioinformatics</kwd>
<kwd>influenza A virus</kwd>
<kwd>mutational spectra</kwd>
<kwd>polymerase fidelity</kwd>
</kwd-group>
<funding-group><award-group id="award1"><funding-source id="GS1">NIAID</funding-source>
<award-id>NIAID contract HHSN272201400006C</award-id>
</award-group>
<award-group id="award2"><funding-source id="GS2">University Grants Committee</funding-source>
<award-id>AoE/M-12/06</award-id>
</award-group>
<award-group id="award3"><funding-source id="GS3">US Department Health and Human Services</funding-source>
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