📄 Genome-wide screen reveals valosin-containing protein requirement for coronavirus exit from endosomes

© 2015, American Society for Microbiology. 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.

keywords 🔗 severe acute (1373) 🔗 bronchitis virus (233) 🔗 public health (392) 🔗 viral proteins (89) 🔗 poorly understood (52) 🔗 infectious bronchitis (235) 🔗 respiratory syndrome (2004) 🔗 acute respiratory (1734)

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