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Determining the Mutation Bias of Favipiravir in Influenza Virus Using Next-Generation Sequencing

Identifieur interne : 000080 ( Pmc/Checkpoint ); précédent : 000079; suivant : 000081

Determining the Mutation Bias of Favipiravir in Influenza Virus Using Next-Generation Sequencing

Auteurs : Daniel H. Goldhill [Royaume-Uni] ; Pinky Langat [Royaume-Uni] ; Hongyao Xie [Royaume-Uni] ; Monica Galiano [Royaume-Uni] ; Shahjahan Miah [Royaume-Uni] ; Paul Kellam [Royaume-Uni] ; Maria Zambon [Royaume-Uni] ; Angie Lackenby [Royaume-Uni] ; Wendy S. Barclay [Royaume-Uni]

Source :

RBID : PMC:6321902

Abstract

New antiviral drugs are needed as a first line of defense in the event of a novel influenza pandemic. Favipiravir is a broad-spectrum antiviral which is effective against influenza. The exact mechanism of how favipiravir works to inhibit influenza is still unclear. We used next-generation sequencing (NGS) to demonstrate that favipiravir causes mutations in influenza RNA. The greater depth of NGS sequence information over traditional sequencing methods allowed us to precisely determine the bias of particular mutations caused by favipiravir. NGS can also be used in a standard diagnostic pipeline to show that favipiravir is acting on the virus by revealing the mutation bias pattern typical to the drug. Our work will aid in testing whether viruses are resistant to favipiravir and may help demonstrate the effect of favipiravir on viruses in a clinical setting. This will be important if favipiravir is used during a future influenza pandemic.


Url:
DOI: 10.1128/JVI.01217-18
PubMed: 30381482
PubMed Central: 6321902


Affiliations:


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PMC:6321902

Le document en format XML

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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">J Virol</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Virol</journal-id>
<journal-id journal-id-type="hwp">jvi</journal-id>
<journal-id journal-id-type="pmc">jvi</journal-id>
<journal-id journal-id-type="publisher-id">JVI</journal-id>
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<journal-title>Journal of Virology</journal-title>
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<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher>
<publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
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<article-meta>
<article-id pub-id-type="pmid">30381482</article-id>
<article-id pub-id-type="pmc">6321902</article-id>
<article-id pub-id-type="publisher-id">01217-18</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01217-18</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Vaccines and Antiviral Agents</subject>
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<title-group>
<article-title>Determining the Mutation Bias of Favipiravir in Influenza Virus Using Next-Generation Sequencing</article-title>
<alt-title alt-title-type="running-head">Mutation Bias of Favipiravir in Flu Using NGS</alt-title>
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<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0003-4597-5963</contrib-id>
<name>
<surname>Goldhill</surname>
<given-names>Daniel H.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Langat</surname>
<given-names>Pinky</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Xie</surname>
<given-names>Hongyao</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Galiano</surname>
<given-names>Monica</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Miah</surname>
<given-names>Shahjahan</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kellam</surname>
<given-names>Paul</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zambon</surname>
<given-names>Maria</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lackenby</surname>
<given-names>Angie</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Barclay</surname>
<given-names>Wendy S.</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<aff id="aff1">
<label>a</label>
<addr-line>Public Health England, London, United Kingdom</addr-line>
</aff>
<aff id="aff2">
<label>b</label>
<addr-line>Department of Virology, Faculty of Medicine, Imperial College, London, United Kingdom</addr-line>
</aff>
</contrib-group>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>García-Sastre</surname>
<given-names>Adolfo</given-names>
</name>
<role>Editor</role>
<aff>Icahn School of Medicine at Mount Sinai</aff>
</contrib>
</contrib-group>
<author-notes>
<corresp id="cor1">Address correspondence to Wendy S. Barclay,
<email>w.barclay@imperial.ac.uk</email>
.</corresp>
<fn fn-type="other">
<p>
<bold>Citation</bold>
Goldhill DH, Langat P, Xie H, Galiano M, Miah S, Kellam P, Zambon M, Lackenby A, Barclay WS. 2019. Determining the mutation bias of favipiravir in influenza virus using next-generation sequencing. J Virol 93:e01217-18.
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/JVI.01217-18">https://doi.org/10.1128/JVI.01217-18</ext-link>
.</p>
</fn>
</author-notes>
<pub-date pub-type="epreprint">
<day>31</day>
<month>10</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="epub">
<day>4</day>
<month>1</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection">
<day>15</day>
<month>1</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>4</day>
<month>1</month>
<year>2019</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>93</volume>
<issue>2</issue>
<elocation-id>e01217-18</elocation-id>
<history>
<date date-type="received">
<day>12</day>
<month>7</month>
<year>2018</year>
</date>
<date date-type="accepted">
<day>21</day>
<month>10</month>
<year>2018</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2019 Goldhill et al.</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Goldhill et al.</copyright-holder>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open-access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>
.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="JVI.01217-18.pdf"></self-uri>
<abstract abstract-type="precis">
<p>New antiviral drugs are needed as a first line of defense in the event of a novel influenza pandemic. Favipiravir is a broad-spectrum antiviral which is effective against influenza. The exact mechanism of how favipiravir works to inhibit influenza is still unclear. We used next-generation sequencing (NGS) to demonstrate that favipiravir causes mutations in influenza RNA. The greater depth of NGS sequence information over traditional sequencing methods allowed us to precisely determine the bias of particular mutations caused by favipiravir. NGS can also be used in a standard diagnostic pipeline to show that favipiravir is acting on the virus by revealing the mutation bias pattern typical to the drug. Our work will aid in testing whether viruses are resistant to favipiravir and may help demonstrate the effect of favipiravir on viruses in a clinical setting. This will be important if favipiravir is used during a future influenza pandemic.</p>
</abstract>
<abstract>
<title>ABSTRACT</title>
<p>Favipiravir is a broad-spectrum antiviral drug that may be used to treat influenza. Previous research has identified that favipiravir likely acts as a mutagen, but the precise mutation bias that favipiravir induces in influenza virus RNAs has not been described. Here, we use next-generation sequencing (NGS) with barcoding of individual RNA molecules to accurately and quantitatively detect favipiravir-induced mutations and to sample orders of magnitude more mutations than would be possible through Sanger sequencing. We demonstrate that favipiravir causes mutations and show that favipiravir primarily acts as a guanine analogue and secondarily as an adenine analogue resulting in the accumulation of transition mutations. We also use a standard NGS pipeline to show that the mutagenic effect of favipiravir can be measured by whole-genome sequencing of virus.</p>
<p>
<bold>IMPORTANCE</bold>
New antiviral drugs are needed as a first line of defense in the event of a novel influenza pandemic. Favipiravir is a broad-spectrum antiviral which is effective against influenza. The exact mechanism of how favipiravir works to inhibit influenza is still unclear. We used next-generation sequencing (NGS) to demonstrate that favipiravir causes mutations in influenza RNA. The greater depth of NGS sequence information over traditional sequencing methods allowed us to precisely determine the bias of particular mutations caused by favipiravir. NGS can also be used in a standard diagnostic pipeline to show that favipiravir is acting on the virus by revealing the mutation bias pattern typical to the drug. Our work will aid in testing whether viruses are resistant to favipiravir and may help demonstrate the effect of favipiravir on viruses in a clinical setting. This will be important if favipiravir is used during a future influenza pandemic.</p>
</abstract>
<kwd-group>
<title>KEYWORDS</title>
<kwd>favipiravir</kwd>
<kwd>mutation bias</kwd>
<kwd>next-generation sequencing</kwd>
<kwd>Primer ID</kwd>
<kwd>influenza</kwd>
</kwd-group>
<funding-group>
<award-group id="award1">
<funding-source>
<institution-wrap>
<institution>Wellcome Trust</institution>
</institution-wrap>
</funding-source>
<award-id>200187/Z/15/Z</award-id>
<principal-award-recipient>
<name>
<surname>Barclay</surname>
<given-names>Wendy S.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award2">
<funding-source>
<institution-wrap>
<institution>HPRU in Respiratory Infections</institution>
</institution-wrap>
</funding-source>
<principal-award-recipient>
<name>
<surname>Goldhill</surname>
<given-names>Daniel H.</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<counts>
<fig-count count="7"></fig-count>
<table-count count="0"></table-count>
<equation-count count="0"></equation-count>
<ref-count count="50"></ref-count>
<page-count count="13"></page-count>
<word-count count="8599"></word-count>
</counts>
<custom-meta-group>
<custom-meta>
<meta-name>cover-date</meta-name>
<meta-value>January 2019</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>Royaume-Uni</li>
</country>
<region>
<li>Angleterre</li>
<li>Grand Londres</li>
</region>
<settlement>
<li>Londres</li>
</settlement>
</list>
<tree>
<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Goldhill, Daniel H" sort="Goldhill, Daniel H" uniqKey="Goldhill D" first="Daniel H." last="Goldhill">Daniel H. Goldhill</name>
</region>
<name sortKey="Barclay, Wendy S" sort="Barclay, Wendy S" uniqKey="Barclay W" first="Wendy S." last="Barclay">Wendy S. Barclay</name>
<name sortKey="Galiano, Monica" sort="Galiano, Monica" uniqKey="Galiano M" first="Monica" last="Galiano">Monica Galiano</name>
<name sortKey="Goldhill, Daniel H" sort="Goldhill, Daniel H" uniqKey="Goldhill D" first="Daniel H." last="Goldhill">Daniel H. Goldhill</name>
<name sortKey="Kellam, Paul" sort="Kellam, Paul" uniqKey="Kellam P" first="Paul" last="Kellam">Paul Kellam</name>
<name sortKey="Lackenby, Angie" sort="Lackenby, Angie" uniqKey="Lackenby A" first="Angie" last="Lackenby">Angie Lackenby</name>
<name sortKey="Langat, Pinky" sort="Langat, Pinky" uniqKey="Langat P" first="Pinky" last="Langat">Pinky Langat</name>
<name sortKey="Miah, Shahjahan" sort="Miah, Shahjahan" uniqKey="Miah S" first="Shahjahan" last="Miah">Shahjahan Miah</name>
<name sortKey="Xie, Hongyao" sort="Xie, Hongyao" uniqKey="Xie H" first="Hongyao" last="Xie">Hongyao Xie</name>
<name sortKey="Zambon, Maria" sort="Zambon, Maria" uniqKey="Zambon M" first="Maria" last="Zambon">Maria Zambon</name>
</country>
</tree>
</affiliations>
</record>

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