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

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.

• Authors: Holly R Ramage, G Renuka Kumar, Erik Verschueren, Jeffrey R Johnson, John Von Dollen, Tasha Johnson, Billy Newton, Priya Shah, Julie Horner, Nevan J Krogan, Melanie Ott
• Journal: Molecular cell (Mol Cell) Vol. 57 Issue 2 Pg. 329-340 (Jan 22 2015) ISSN: 1097-4164 [Electronic] United States
• PMID: 25616068 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Carrier Proteins
• Intracellular Signaling Peptides and Proteins
• Mitochondrial Proteins
• NS4A cofactor peptide, Hepatitis C virus
• NS4B protein, flavivirus
• Proteome
• VAPA protein, human
• VAPB protein, human
• Vesicular Transport Proteins
• Viral Core Proteins
• Viral Nonstructural Proteins

Topics

• Carrier Proteins (metabolism)
• Cell Line, Tumor
• Hepacivirus (physiology)
• Hepatitis C (metabolism, virology)
• Host-Pathogen Interactions
• Humans
• Intracellular Signaling Peptides and Proteins
• Mitochondria (metabolism)
• Mitochondrial Proteins (metabolism)
• Nonsense Mediated mRNA Decay
• Protein Interaction Maps
• Protein Transport
• Proteome (metabolism)
• Proteomics
• Vesicular Transport Proteins (metabolism)
• Viral Core Proteins (metabolism)
• Viral Nonstructural Proteins (metabolism)