Budding Capability of the Influenza Virus Neuraminidase Can Be Modulated by Tetherin▿
Identifieur interne : 000850 ( Pmc/Checkpoint ); précédent : 000849; suivant : 000851Budding Capability of the Influenza Virus Neuraminidase Can Be Modulated by Tetherin▿
Auteurs : Mark A. Yondola ; Fiona Fernandes ; Alan Belicha-Villanueva ; Melissa Uccelini ; Qinshan Gao ; Carol Carter ; Peter PaleseSource :
- Journal of Virology [ 0022-538X ] ; 2011.
Abstract
We have determined that, in addition to its receptor-destroying activity, the influenza virus neuraminidase is capable of efficiently forming virus-like particles (VLPs) when expressed individually from plasmid DNA. This observation applies to both human subtypes of neuraminidase, N1 and N2. However, it is not found with every strain of influenza virus. Through gain-of-function and loss-of-function analyses, a critical determinant within the neuraminidase ectodomain was identified that contributes to VLP formation but is not sufficient to accomplish release of plasmid-derived VLPs. This sequence lies on the plasma membrane-proximal side of the neuraminidase globular head. Most importantly, we demonstrate that the antiviral restriction factor tetherin plays a role in determining the strain-specific limitations of release competency. If tetherin is counteracted by small interfering RNA knockdown or expression of the HIV anti-tetherin factor vpu, budding and release capability is bestowed upon an otherwise budding-deficient neuraminidase. These data suggest that budding-competent neuraminidase proteins possess an as-yet-unidentified means of counteracting the antiviral restriction factor tetherin and identify a novel way in which the influenza virus neuraminidase can contribute to virus release.
Url:
DOI: 10.1128/JVI.02188-10
PubMed: 21209114
PubMed Central: 3067929
Affiliations:
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<series><title level="j">Journal of Virology</title>
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<front><div type="abstract" xml:lang="en"><p>We have determined that, in addition to its receptor-destroying activity, the influenza virus neuraminidase is capable of efficiently forming virus-like particles (VLPs) when expressed individually from plasmid DNA. This observation applies to both human subtypes of neuraminidase, N1 and N2. However, it is not found with every strain of influenza virus. Through gain-of-function and loss-of-function analyses, a critical determinant within the neuraminidase ectodomain was identified that contributes to VLP formation but is not sufficient to accomplish release of plasmid-derived VLPs. This sequence lies on the plasma membrane-proximal side of the neuraminidase globular head. Most importantly, we demonstrate that the antiviral restriction factor tetherin plays a role in determining the strain-specific limitations of release competency. If tetherin is counteracted by small interfering RNA knockdown or expression of the HIV anti-tetherin factor vpu, budding and release capability is bestowed upon an otherwise budding-deficient neuraminidase. These data suggest that budding-competent neuraminidase proteins possess an as-yet-unidentified means of counteracting the antiviral restriction factor tetherin and identify a novel way in which the influenza virus neuraminidase can contribute to virus release.</p>
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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>
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<article-id pub-id-type="pmc">3067929</article-id>
<article-id pub-id-type="publisher-id">2188-10</article-id>
<article-id pub-id-type="doi">10.1128/JVI.02188-10</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Virus-Cell Interactions</subject>
</subj-group>
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<title-group><article-title>Budding Capability of the Influenza Virus Neuraminidase Can Be Modulated by Tetherin<xref ref-type="fn" rid="fn1">▿</xref>
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</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Yondola</surname>
<given-names>Mark A.</given-names>
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<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
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<contrib contrib-type="author"><name><surname>Fernandes</surname>
<given-names>Fiona</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
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<contrib contrib-type="author"><name><surname>Belicha-Villanueva</surname>
<given-names>Alan</given-names>
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<contrib contrib-type="author"><name><surname>Uccelini</surname>
<given-names>Melissa</given-names>
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<xref ref-type="aff" rid="aff1">1</xref>
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<contrib contrib-type="author"><name><surname>Gao</surname>
<given-names>Qinshan</given-names>
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<xref ref-type="aff" rid="aff1">1</xref>
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<contrib contrib-type="author"><name><surname>Carter</surname>
<given-names>Carol</given-names>
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<contrib contrib-type="author"><name><surname>Palese</surname>
<given-names>Peter</given-names>
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<aff id="aff1">Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Department of Microbiology, Annenberg Bldg. 16-20, New York, New York 10128,<label>1</label>
Stony Brook University, Life Sciences Bldg., Stony Brook, New York 11794<label>2</label>
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<author-notes><corresp id="cor1"><label>*</label>
Corresponding author. Mailing address: Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Department of Microbiology, Annenberg Bldg. 16-20, New York, NY 10128. Phone: (212) 241-7094. Fax: (212) 534-1684. E-mail: <email>mark.yondola@mssm.edu</email>
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<pub-date pub-type="ppub"><month>3</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>5</day>
<month>1</month>
<year>2011</year>
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<volume>85</volume>
<issue>6</issue>
<fpage>2480</fpage>
<lpage>2491</lpage>
<history><date date-type="received"><day>18</day>
<month>10</month>
<year>2010</year>
</date>
<date date-type="accepted"><day>28</day>
<month>12</month>
<year>2010</year>
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<permissions><copyright-statement>Copyright © 2011, American Society for Microbiology</copyright-statement>
<copyright-year>2011</copyright-year>
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<abstract><p>We have determined that, in addition to its receptor-destroying activity, the influenza virus neuraminidase is capable of efficiently forming virus-like particles (VLPs) when expressed individually from plasmid DNA. This observation applies to both human subtypes of neuraminidase, N1 and N2. However, it is not found with every strain of influenza virus. Through gain-of-function and loss-of-function analyses, a critical determinant within the neuraminidase ectodomain was identified that contributes to VLP formation but is not sufficient to accomplish release of plasmid-derived VLPs. This sequence lies on the plasma membrane-proximal side of the neuraminidase globular head. Most importantly, we demonstrate that the antiviral restriction factor tetherin plays a role in determining the strain-specific limitations of release competency. If tetherin is counteracted by small interfering RNA knockdown or expression of the HIV anti-tetherin factor vpu, budding and release capability is bestowed upon an otherwise budding-deficient neuraminidase. These data suggest that budding-competent neuraminidase proteins possess an as-yet-unidentified means of counteracting the antiviral restriction factor tetherin and identify a novel way in which the influenza virus neuraminidase can contribute to virus release.</p>
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<tree><noCountry><name sortKey="Belicha Villanueva, Alan" sort="Belicha Villanueva, Alan" uniqKey="Belicha Villanueva A" first="Alan" last="Belicha-Villanueva">Alan Belicha-Villanueva</name>
<name sortKey="Carter, Carol" sort="Carter, Carol" uniqKey="Carter C" first="Carol" last="Carter">Carol Carter</name>
<name sortKey="Fernandes, Fiona" sort="Fernandes, Fiona" uniqKey="Fernandes F" first="Fiona" last="Fernandes">Fiona Fernandes</name>
<name sortKey="Gao, Qinshan" sort="Gao, Qinshan" uniqKey="Gao Q" first="Qinshan" last="Gao">Qinshan Gao</name>
<name sortKey="Palese, Peter" sort="Palese, Peter" uniqKey="Palese P" first="Peter" last="Palese">Peter Palese</name>
<name sortKey="Uccelini, Melissa" sort="Uccelini, Melissa" uniqKey="Uccelini M" first="Melissa" last="Uccelini">Melissa Uccelini</name>
<name sortKey="Yondola, Mark A" sort="Yondola, Mark A" uniqKey="Yondola M" first="Mark A." last="Yondola">Mark A. Yondola</name>
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