Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes
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 replic...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2015
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| Online Access: | https://hdl.handle.net/10356/80970 http://hdl.handle.net/10220/38942 |
| _version_ | 1811680879175532544 |
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| author | Wong, Hui Hui Kumar, Pankaj Tay, Felicia Pei Ling Moreau, Dimitri Liu, Ding Xiang Bard, Frédéric |
| author2 | Perlman, S. |
| author_facet | Perlman, S. Wong, Hui Hui Kumar, Pankaj Tay, Felicia Pei Ling Moreau, Dimitri Liu, Ding Xiang Bard, Frédéric |
| author_sort | Wong, Hui Hui |
| collection | NTU |
| description | 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.
IMPORTANCE 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. |
| first_indexed | 2024-10-01T03:32:03Z |
| format | Journal Article |
| id | ntu-10356/80970 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:32:03Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/809702023-02-28T16:56:20Z Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes Wong, Hui Hui Kumar, Pankaj Tay, Felicia Pei Ling Moreau, Dimitri Liu, Ding Xiang Bard, Frédéric Perlman, S. School of Biological Sciences 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. IMPORTANCE 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. Published version 2015-12-03T07:19:09Z 2019-12-06T14:18:36Z 2015-12-03T07:19:09Z 2019-12-06T14:18:36Z 2015 Journal Article Wong, H. H., Kumar, P., Tay, F. P. L., Moreau, D., Liu, D. X., & Bard, F. (2015). Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes. Journal of Virology, 89(21), 11116-11128. 0022-538X https://hdl.handle.net/10356/80970 http://hdl.handle.net/10220/38942 10.1128/JVI.01360-15 26311884 en Journal of Virology © 2015 American Society for Microbiology. This paper was published in Journal of Virology and is made available as an electronic reprint (preprint) with permission of American Society for Microbiology. The published version is available at: [http://dx.doi.org/10.1128/JVI.01360-15]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. 13 p. application/pdf |
| spellingShingle | Wong, Hui Hui Kumar, Pankaj Tay, Felicia Pei Ling Moreau, Dimitri Liu, Ding Xiang Bard, Frédéric Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes |
| title | Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes |
| title_full | Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes |
| title_fullStr | Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes |
| title_full_unstemmed | Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes |
| title_short | Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes |
| title_sort | genome wide screen reveals valosin containing protein requirement for coronavirus exit from endosomes |
| url | https://hdl.handle.net/10356/80970 http://hdl.handle.net/10220/38942 |
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