Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes
Identifieur interne : 002B17 ( Ncbi/Merge ); précédent : 002B16; suivant : 002B18Genome-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.
Descripteurs français
- KwdFr :
- Adenosine triphosphatases (génétique), Adenosine triphosphatases (métabolisme), Animaux, Annotation de séquence moléculaire, Cellules Vero, Endosomes (virologie), Humains, Infections à coronavirus (transmission), Libération de particules virales (physiologie), Lignée cellulaire, Petit ARN interférent (génétique), Protéines du cycle cellulaire (génétique), Protéines du cycle cellulaire (métabolisme), Technique d'immunofluorescence, Technique de Western, Virus de la bronchite infectieuse (physiologie), Étude d'association pangénomique.
- MESH :
- génétique : Adenosine triphosphatases, Petit ARN interférent, Protéines du cycle cellulaire.
- métabolisme : Adenosine triphosphatases, Protéines du cycle cellulaire.
- physiologie : Libération de particules virales, Virus de la bronchite infectieuse.
- virologie : Endosomes.
- transmission : Animaux, Annotation de séquence moléculaire, Cellules Vero, Humains, Infections à coronavirus, Lignée cellulaire, Technique d'immunofluorescence, Technique de Western, Étude d'association pangénomique.
English descriptors
- KwdEn :
- Adenosine Triphosphatases (genetics), Adenosine Triphosphatases (metabolism), Animals, Blotting, Western, Cell Cycle Proteins (genetics), Cell Cycle Proteins (metabolism), Cell Line, Chlorocebus aethiops, Coronavirus Infections (transmission), Endosomes (virology), Fluorescent Antibody Technique, Genome-Wide Association Study, Humans, Infectious bronchitis virus (physiology), Molecular Sequence Annotation, RNA, Small Interfering (genetics), Valosin Containing Protein, Vero Cells, Virus Release (physiology).
- MESH :
- chemical , genetics : Adenosine Triphosphatases, Cell Cycle Proteins, RNA, Small Interfering.
- chemical , metabolism : Adenosine Triphosphatases, Cell Cycle Proteins.
- physiology : Infectious bronchitis virus, Virus Release.
- transmission : Coronavirus Infections.
- virology : Endosomes.
- Animals, Blotting, Western, Cell Line, Chlorocebus aethiops, Fluorescent Antibody Technique, Genome-Wide Association Study, Humans, Molecular Sequence Annotation, Valosin Containing Protein, Vero Cells.
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
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<term>Annotation de séquence moléculaire</term>
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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>
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<author><name sortKey="Wong, Hui Hui" sort="Wong, Hui Hui" uniqKey="Wong H" first="Hui Hui" last="Wong">Hui Hui Wong</name>
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<affiliation wicri:level="4"><nlm:aff id="aff2">Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore</nlm:aff>
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<wicri:regionArea>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</wicri:regionArea>
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</author>
<author><name sortKey="Kumar, Pankaj" sort="Kumar, Pankaj" uniqKey="Kumar P" first="Pankaj" last="Kumar">Pankaj Kumar</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Molecular and Cell Biology/A*STAR, Singapore, Singapore</nlm:aff>
<country xml:lang="fr">Singapour</country>
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<wicri:noRegion>Singapore</wicri:noRegion>
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</author>
<author><name sortKey="Tay, Felicia Pei Ling" sort="Tay, Felicia Pei Ling" uniqKey="Tay F" first="Felicia Pei Ling" last="Tay">Felicia Pei Ling Tay</name>
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<author><name sortKey="Moreau, Dimitri" sort="Moreau, Dimitri" uniqKey="Moreau D" first="Dimitri" last="Moreau">Dimitri Moreau</name>
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</author>
<author><name sortKey="Liu, Ding Xiang" sort="Liu, Ding Xiang" uniqKey="Liu D" first="Ding Xiang" last="Liu">Ding Xiang Liu</name>
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<wicri:noRegion>Singapore</wicri:noRegion>
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<affiliation wicri:level="1"><nlm:aff id="aff3">School of Biological Sciences, Nanyang Technological University, Singapore, Singapore</nlm:aff>
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</author>
<author><name sortKey="Bard, Frederic" sort="Bard, Frederic" uniqKey="Bard F" first="Frédéric" last="Bard">Frédéric Bard</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Institute of Molecular and Cell Biology/A*STAR, Singapore, Singapore</nlm:aff>
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<wicri:noRegion>Singapore</wicri:noRegion>
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<affiliation wicri:level="4"><nlm:aff id="aff2">Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore</nlm:aff>
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<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
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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>
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<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes.</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes.</title>
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<author><name sortKey="Kumar, Pankaj" sort="Kumar, Pankaj" uniqKey="Kumar P" first="Pankaj" last="Kumar">Pankaj Kumar</name>
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<term>Cell Cycle Proteins (genetics)</term>
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<term>Infections à coronavirus (transmission)</term>
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<front><div type="abstract" xml:lang="en">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.</div>
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