Strain-specific antiviral activity of iminosugars against human influenza A viruses
Identifieur interne : 000665 ( Main/Exploration ); précédent : 000664; suivant : 000666Strain-specific antiviral activity of iminosugars against human influenza A viruses
Auteurs : S. Hussain [Royaume-Uni] ; J. L. Miller [Royaume-Uni] ; D. J. Harvey [Royaume-Uni] ; Y. Gu [Royaume-Uni] ; P. B. Rosenthal [Royaume-Uni] ; N. Zitzmann [Royaume-Uni] ; J. W. Mccauley [Royaume-Uni]Source :
- Journal of Antimicrobial Chemotherapy [ 0305-7453 ] ; 2014.
Abstract
Drugs that target host cell processes can be employed to complement drugs that specifically target viruses, and iminosugar compounds that inhibit host α-glucosidases have been reported to show antiviral activity against multiple viruses. Here the effect and mechanism of two iminosugar α-glucosidase inhibitors,
The viruses examined were a recently circulating seasonal influenza A(H3N2) virus strain A/Brisbane/10/2007, an older H3N2 strain A/Udorn/307/72, and A/Lviv/N6/2009, a strain representative of the currently circulating pandemic influenza A(H1N1)pdm09 virus.
The inhibitors had the strongest effect on Brisbane/10 and
Url:
DOI: 10.1093/jac/dku349
PubMed: 25223974
PubMed Central: 4267503
Affiliations:
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Hussain</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Division of Virology</addr-line>,<institution>Medical Research Council National Institute for Medical Research</institution>,<addr-line>Mill Hill, London NW7 1AA</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Division of Physical Biochemistry</addr-line>,<institution>Medical Research Council National Institute for Medical Research</institution>,<addr-line>Mill Hill, London NW7 1AA</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Miller, J L" sort="Miller, J L" uniqKey="Miller J" first="J. L." last="Miller">J. L. Miller</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Oxford Glycobiology Institute, Department of Biochemistry</addr-line>,<institution>University of Oxford</institution>,<addr-line>South Parks Road, Oxford OX1 3QU</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Harvey, D J" sort="Harvey, D J" uniqKey="Harvey D" first="D. J." last="Harvey">D. J. Harvey</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Oxford Glycobiology Institute, Department of Biochemistry</addr-line>,<institution>University of Oxford</institution>,<addr-line>South Parks Road, Oxford OX1 3QU</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Biological Sciences, Gibbet Hill Campus</addr-line>,<institution>University of Warwick</institution>,<addr-line>Coventry CV4 7AL</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gu, Y" sort="Gu, Y" uniqKey="Gu Y" first="Y." last="Gu">Y. Gu</name><affiliation wicri:level="1"><nlm:aff id="af5"><addr-line>Confocal Imaging and Analysis Laboratory</addr-line>,<institution>Medical Research Council National Institute for Medical Research</institution>,<addr-line>Mill Hill, London NW7 1AA</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rosenthal, P B" sort="Rosenthal, P B" uniqKey="Rosenthal P" first="P. B." last="Rosenthal">P. B. Rosenthal</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Division of Physical Biochemistry</addr-line>,<institution>Medical Research Council National Institute for Medical Research</institution>,<addr-line>Mill Hill, London NW7 1AA</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zitzmann, N" sort="Zitzmann, N" uniqKey="Zitzmann N" first="N." last="Zitzmann">N. Zitzmann</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Oxford Glycobiology Institute, Department of Biochemistry</addr-line>,<institution>University of Oxford</institution>,<addr-line>South Parks Road, Oxford OX1 3QU</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mccauley, J W" sort="Mccauley, J W" uniqKey="Mccauley J" first="J. W." last="Mccauley">J. W. Mccauley</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Division of Virology</addr-line>,<institution>Medical Research Council National Institute for Medical Research</institution>,<addr-line>Mill Hill, London NW7 1AA</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25223974</idno><idno type="pmc">4267503</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267503</idno><idno type="RBID">PMC:4267503</idno><idno type="doi">10.1093/jac/dku349</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000997</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000997</idno><idno type="wicri:Area/Pmc/Curation">000997</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000997</idno><idno type="wicri:Area/Pmc/Checkpoint">000452</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000452</idno><idno type="wicri:Area/Ncbi/Merge">000A85</idno><idno type="wicri:Area/Ncbi/Curation">000A85</idno><idno type="wicri:Area/Ncbi/Checkpoint">000A85</idno><idno type="wicri:doubleKey">0305-7453:2014:Hussain S:strain:specific:antiviral</idno><idno type="wicri:Area/Main/Merge">000666</idno><idno type="wicri:Area/Main/Curation">000665</idno><idno type="wicri:Area/Main/Exploration">000665</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Strain-specific antiviral activity of iminosugars against human influenza A viruses</title><author><name sortKey="Hussain, S" sort="Hussain, S" uniqKey="Hussain S" first="S." last="Hussain">S. Hussain</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Division of Virology</addr-line>,<institution>Medical Research Council National Institute for Medical Research</institution>,<addr-line>Mill Hill, London NW7 1AA</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Division of Physical Biochemistry</addr-line>,<institution>Medical Research Council National Institute for Medical Research</institution>,<addr-line>Mill Hill, London NW7 1AA</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Miller, J L" sort="Miller, J L" uniqKey="Miller J" first="J. L." last="Miller">J. L. Miller</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Oxford Glycobiology Institute, Department of Biochemistry</addr-line>,<institution>University of Oxford</institution>,<addr-line>South Parks Road, Oxford OX1 3QU</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Harvey, D J" sort="Harvey, D J" uniqKey="Harvey D" first="D. J." last="Harvey">D. J. Harvey</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Oxford Glycobiology Institute, Department of Biochemistry</addr-line>,<institution>University of Oxford</institution>,<addr-line>South Parks Road, Oxford OX1 3QU</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Biological Sciences, Gibbet Hill Campus</addr-line>,<institution>University of Warwick</institution>,<addr-line>Coventry CV4 7AL</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gu, Y" sort="Gu, Y" uniqKey="Gu Y" first="Y." last="Gu">Y. Gu</name><affiliation wicri:level="1"><nlm:aff id="af5"><addr-line>Confocal Imaging and Analysis Laboratory</addr-line>,<institution>Medical Research Council National Institute for Medical Research</institution>,<addr-line>Mill Hill, London NW7 1AA</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rosenthal, P B" sort="Rosenthal, P B" uniqKey="Rosenthal P" first="P. B." last="Rosenthal">P. B. Rosenthal</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Division of Physical Biochemistry</addr-line>,<institution>Medical Research Council National Institute for Medical Research</institution>,<addr-line>Mill Hill, London NW7 1AA</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zitzmann, N" sort="Zitzmann, N" uniqKey="Zitzmann N" first="N." last="Zitzmann">N. Zitzmann</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Oxford Glycobiology Institute, Department of Biochemistry</addr-line>,<institution>University of Oxford</institution>,<addr-line>South Parks Road, Oxford OX1 3QU</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mccauley, J W" sort="Mccauley, J W" uniqKey="Mccauley J" first="J. W." last="Mccauley">J. W. Mccauley</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Division of Virology</addr-line>,<institution>Medical Research Council National Institute for Medical Research</institution>,<addr-line>Mill Hill, London NW7 1AA</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Antimicrobial Chemotherapy</title><idno type="ISSN">0305-7453</idno><idno type="eISSN">1460-2091</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objectives</title><p>Drugs that target host cell processes can be employed to complement drugs that specifically target viruses, and iminosugar compounds that inhibit host α-glucosidases have been reported to show antiviral activity against multiple viruses. Here the effect and mechanism of two iminosugar α-glucosidase inhibitors, <italic>N</italic>-butyl-deoxynojirimycin (<italic>N</italic>B-DNJ) and <italic>N</italic>-nonyl-deoxynojirimycin (<italic>N</italic>N-DNJ), on human influenza A viruses was examined.</p></sec><sec><title>Methods</title><p>The viruses examined were a recently circulating seasonal influenza A(H3N2) virus strain A/Brisbane/10/2007, an older H3N2 strain A/Udorn/307/72, and A/Lviv/N6/2009, a strain representative of the currently circulating pandemic influenza A(H1N1)pdm09 virus.</p></sec><sec><title>Results</title><p>The inhibitors had the strongest effect on Brisbane/10 and <italic>N</italic>N-DNJ was more potent than <italic>N</italic>B-DNJ. Both compounds showed antiviral activity in cell culture against three human influenza A viruses in a strain-specific manner. Consistent with its action as an α-glucosidase inhibitor, <italic>N</italic>N-DNJ treatment resulted in an altered glycan processing of influenza haemagglutinin (HA) and neuraminidase (NA), confirmed by MS. <italic>N</italic>N-DNJ treatment was found to reduce the cell surface expression of the H3 subtype HA. The level of sialidase activity of NA was reduced in infected cells, but the addition of exogenous sialidase to the cells did not complement the <italic>N</italic>N-DNJ-mediated inhibition of virus replication. Using reassortant viruses, the drug susceptibility profile was determined to correlate with the origin of the HA.</p></sec><sec><title>Conclusions</title><p><italic>N</italic>N-DNJ inhibits influenza A virus replication in a strain-specific manner that is dependent on the HA.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Johnson, N" uniqKey="Johnson N">N Johnson</name></author><author><name sortKey="Mueller, J" uniqKey="Mueller J">J Mueller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dawood, Fs" uniqKey="Dawood F">FS Dawood</name></author><author><name sortKey="Iuliano, Ad" uniqKey="Iuliano A">AD Iuliano</name></author><author><name sortKey="Reed, C" uniqKey="Reed C">C Reed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Skehel, Jj" uniqKey="Skehel J">JJ Skehel</name></author><author><name sortKey="Wiley, Dc" uniqKey="Wiley D">DC 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Hussain</name></noRegion><name sortKey="Gu, Y" sort="Gu, Y" uniqKey="Gu Y" first="Y." last="Gu">Y. Gu</name><name sortKey="Harvey, D J" sort="Harvey, D J" uniqKey="Harvey D" first="D. J." last="Harvey">D. J. Harvey</name><name sortKey="Harvey, D J" sort="Harvey, D J" uniqKey="Harvey D" first="D. J." last="Harvey">D. J. Harvey</name><name sortKey="Hussain, S" sort="Hussain, S" uniqKey="Hussain S" first="S." last="Hussain">S. Hussain</name><name sortKey="Mccauley, J W" sort="Mccauley, J W" uniqKey="Mccauley J" first="J. W." last="Mccauley">J. W. Mccauley</name><name sortKey="Miller, J L" sort="Miller, J L" uniqKey="Miller J" first="J. L." last="Miller">J. L. Miller</name><name sortKey="Rosenthal, P B" sort="Rosenthal, P B" uniqKey="Rosenthal P" first="P. B." last="Rosenthal">P. B. Rosenthal</name><name sortKey="Zitzmann, N" sort="Zitzmann, N" uniqKey="Zitzmann N" first="N." last="Zitzmann">N. 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