title: 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.affiliation: Gladstone Institutes, 1650 Owens Street, San Francisco, CA 94158, USA.|University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Holly R
authors.initials: HR
authors.lastname: Ramage
authors.affiliation: Gladstone Institutes, 1650 Owens Street, San Francisco, CA 94158, USA.|University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: G Renuka
authors.initials: GR
authors.lastname: Kumar
authors.affiliation: University of California, San Francisco, San Francisco, CA 94158, USA.|QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Verschueren
authors.affiliation: Gladstone Institutes, 1650 Owens Street, San Francisco, CA 94158, USA.|University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Johnson
authors.affiliation: University of California, San Francisco, San Francisco, CA 94158, USA.|QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
authors.forename: John
authors.initials: J
authors.lastname: Von Dollen
authors.affiliation: University of California, San Francisco, San Francisco, CA 94158, USA.|QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
authors.forename: Tasha
authors.initials: T
authors.lastname: Johnson
authors.affiliation: University of California, San Francisco, San Francisco, CA 94158, USA.|QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
authors.forename: Billy
authors.initials: B
authors.lastname: Newton
authors.affiliation: University of California, San Francisco, San Francisco, CA 94158, USA.|QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Shah
authors.affiliation: Thermo Fisher Scientific, 355 River Oaks Pkwy, San Jose, CA 95134, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Horner
authors.affiliation: Gladstone Institutes, 1650 Owens Street, San Francisco, CA 94158, USA.|University of California, San Francisco, San Francisco, CA 94158, USA.|QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.affiliation: Gladstone Institutes, 1650 Owens Street, San Francisco, CA 94158, USA.|University of California, San Francisco, San Francisco, CA 94158, USA.|Liver Center, University of California, San Francisco, CA 94143, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Ott
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000378:metabolism* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D059365:Nonsense Mediated mRNA Decay; D060066:Protein Interaction Maps; D021381:Protein Transport; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D033921:Vesicular Transport Proteins / Q000378:metabolism; D014758:Viral Core Proteins / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; C455041:NS4A cofactor peptide, Hepatitis C virus; C080107:NS4B protein, flavivirus; D020543:Proteome; C114051:VAPA protein, human; C496748:VAPB protein, human; D033921:Vesicular Transport Proteins; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins