Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes
Identifieur interne : 000802 ( Pmc/Checkpoint ); précédent : 000801; suivant : 000803Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes
Auteurs : Hui Hui Wong [Singapour] ; Pankaj Kumar [Singapour] ; Felicia Pei Ling Tay [Singapour] ; Dimitri Moreau [Singapour] ; Ding Xiang Liu [Singapour] ; Frédéric Bard [Singapour]Source :
- Journal of Virology [ 0022-538X ] ; 2015.
Abstract
Coronaviruses are RNA viruses with a large zoonotic reservoir and propensity for host switching, representing a real threat for public health, as evidenced by severe acute respiratory syndrome (SARS) and the emerging Middle East respiratory syndrome (MERS). Cellular factors required for their replication are poorly understood. Using genome-wide small interfering RNA (siRNA) screening, we identified 83 novel genes supporting infectious bronchitis virus (IBV) replication in human cells. Thirty of these hits can be placed in a network of interactions with viral proteins and are involved in RNA splicing, membrane trafficking, and ubiquitin conjugation. In addition, our screen reveals an unexpected role for valosin-containing protein (VCP/p97) in early steps of infection. Loss of VCP inhibits a previously uncharacterized degradation of the nucleocapsid N protein. This inhibition derives from virus accumulation in early endosomes, suggesting a role for VCP in the maturation of virus-loaded endosomes. The several host factors identified in this study may provide avenues for targeted therapeutics.
Url:
DOI: 10.1128/JVI.01360-15
PubMed: 26311884
PubMed Central: 4621105
Affiliations:
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<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>Coronaviruses are RNA viruses with a large zoonotic reservoir and propensity for host switching, representing a real threat for public health, as evidenced by severe acute respiratory syndrome (SARS) and the emerging Middle East respiratory syndrome (MERS). Cellular factors required for their replication are poorly understood. Using genome-wide small interfering RNA (siRNA) screening, we identified 83 novel genes supporting infectious bronchitis virus (IBV) replication in human cells. Thirty of these hits can be placed in a network of interactions with viral proteins and are involved in RNA splicing, membrane trafficking, and ubiquitin conjugation. In addition, our screen reveals an unexpected role for valosin-containing protein (VCP/p97) in early steps of infection. Loss of VCP inhibits a previously uncharacterized degradation of the nucleocapsid N protein. This inhibition derives from virus accumulation in early endosomes, suggesting a role for VCP in the maturation of virus-loaded endosomes. The several host factors identified in this study may provide avenues for targeted therapeutics.</p>
<p><bold>IMPORTANCE</bold>
Coronaviruses are RNA viruses representing a real threat for public health, as evidenced by SARS and the emerging MERS. However, cellular factors required for their replication are poorly understood. Using genome-wide siRNA screening, we identified novel genes supporting infectious bronchitis virus (IBV) replication in human cells. The several host factors identified in this study may provide directions for future research on targeted therapeutics.</p>
</div>
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<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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<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-id pub-id-type="pmc">4621105</article-id>
<article-id pub-id-type="publisher-id">01360-15</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01360-15</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Virus-Cell Interactions</subject>
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</article-categories>
<title-group><article-title>Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes</article-title>
<alt-title alt-title-type="running-head">Host Factors Implicated in Coronavirus Infection</alt-title>
<alt-title alt-title-type="short-authors">Wong et al.</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Wong</surname>
<given-names>Hui Hui</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>Kumar</surname>
<given-names>Pankaj</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tay</surname>
<given-names>Felicia Pei Ling</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moreau</surname>
<given-names>Dimitri</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Liu</surname>
<given-names>Ding Xiang</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Bard</surname>
<given-names>Frédéric</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<aff id="aff1"><label>a</label>
Institute of Molecular and Cell Biology/A*STAR, Singapore, Singapore</aff>
<aff id="aff2"><label>b</label>
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore</aff>
<aff id="aff3"><label>c</label>
School of Biological Sciences, Nanyang Technological University, Singapore, Singapore</aff>
</contrib-group>
<contrib-group><contrib contrib-type="editor"><name><surname>Perlman</surname>
<given-names>S.</given-names>
</name>
<role>Editor</role>
</contrib>
</contrib-group>
<author-notes><corresp id="cor1">Address correspondence to Ding Xiang Liu, <email>dxliu@ntu.edu.sg</email>
, or Frédéric Bard, <email>fbard@imcb.a-star.edu.sg</email>
.</corresp>
<fn fn-type="other"><p><bold>Citation</bold>
Wong HH, Kumar P, Tay FPL, Moreau D, Liu DX, Bard F. 2015. Genome-wide screen reveals valosin-containing protein requirement for coronavirus exit from endosomes. J Virol 89:11116–11128. doi:<ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1128/JVI.01360-15">10.1128/JVI.01360-15</ext-link>
.</p>
</fn>
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<pub-date pub-type="epub"><day>26</day>
<month>8</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="collection"><day>1</day>
<month>11</month>
<year>2015</year>
</pub-date>
<volume>89</volume>
<issue>21</issue>
<fpage>11116</fpage>
<lpage>11128</lpage>
<history><date date-type="received"><day>9</day>
<month>6</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>22</day>
<month>8</month>
<year>2015</year>
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<permissions><copyright-statement>Copyright © 2015, American Society for Microbiology. All Rights Reserved.</copyright-statement>
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<self-uri content-type="pdf" xlink:href="zjv02115011116.pdf"></self-uri>
<abstract><title>ABSTRACT</title>
<p>Coronaviruses are RNA viruses with a large zoonotic reservoir and propensity for host switching, representing a real threat for public health, as evidenced by severe acute respiratory syndrome (SARS) and the emerging Middle East respiratory syndrome (MERS). Cellular factors required for their replication are poorly understood. Using genome-wide small interfering RNA (siRNA) screening, we identified 83 novel genes supporting infectious bronchitis virus (IBV) replication in human cells. Thirty of these hits can be placed in a network of interactions with viral proteins and are involved in RNA splicing, membrane trafficking, and ubiquitin conjugation. In addition, our screen reveals an unexpected role for valosin-containing protein (VCP/p97) in early steps of infection. Loss of VCP inhibits a previously uncharacterized degradation of the nucleocapsid N protein. This inhibition derives from virus accumulation in early endosomes, suggesting a role for VCP in the maturation of virus-loaded endosomes. The several host factors identified in this study may provide avenues for targeted therapeutics.</p>
<p><bold>IMPORTANCE</bold>
Coronaviruses are RNA viruses representing a real threat for public health, as evidenced by SARS and the emerging MERS. However, cellular factors required for their replication are poorly understood. Using genome-wide siRNA screening, we identified novel genes supporting infectious bronchitis virus (IBV) replication in human cells. The several host factors identified in this study may provide directions for future research on targeted therapeutics.</p>
</abstract>
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