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Mol Cell. 2015 Jan 22;57(2):329-340. doi: 10.1016/j.molcel.2014.12.028.

A combined proteomics/genomics approach links hepatitis C virus infection with nonsense-mediated mRNA decay.

Author information

1
Gladstone Institutes, 1650 Owens Street, San Francisco, CA 94158, USA.
2
University of California, San Francisco, San Francisco, CA 94158, USA.
3
QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
4
Thermo Fisher Scientific, 355 River Oaks Pkwy, San Jose, CA 95134, USA.
5
Liver Center, University of California, San Francisco, CA 94143, USA.
#
Contributed equally

Abstract

Hepatitis C virus (HCV) is a leading cause of liver disease, but insight into virus-host interactions remains limited. We systematically used affinity purification/mass spectrometry to define the host interactions of all ten HCV proteins in hepatoma cells. We combined these studies with RNAi knockdown of corresponding genes using a two-step scoring approach to generate a map of 139 high-confidence HCV-host protein-protein interactions. We found mitochondrial proteins highly involved in HCV infection and characterized an interaction between the viral core protein and host protein within bgcn homolog (WIBG). Expression of core prevents WIBG from binding its regular interaction partners Y14 and Magoh, two known mediators of the nonsense-mediated mRNA decay pathway. We discovered that this surveillance pathway is disrupted in HCV-infected cells, causing potentially harmful transcripts to accumulate. Our study provides a comprehensive view of HCV-host interactions and uncovers mechanisms for how HCV perturbs host functions during infection.

PMID:
25616068
PMCID:
PMC4305532
DOI:
10.1016/j.molcel.2014.12.028
[Indexed for MEDLINE]
Free PMC Article

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