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Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry
(Gisa Gerold)
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2015 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 12, no 5, p. 864-878, article id S2211-1247(15)00689-0Article in journal (Refereed) Published
Abstract [en]

Hepatitis C virus (HCV) enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized, and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection, as indicated by RNAi. We further characterized serum response factor binding protein 1 (SRFBP1), which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV-specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion.

Place, publisher, year, edition, pages
2015. Vol. 12, no 5, p. 864-878, article id S2211-1247(15)00689-0
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Immunology in the medical area
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URN: urn:nbn:se:umu:diva-148142DOI: 10.1016/j.celrep.2015.06.063ISI: 000358999800014PubMedID: 26212323OAI: oai:DiVA.org:umu-148142DiVA, id: diva2:1210734
Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2018-10-16Bibliographically approved

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