Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Rep. 2015 Aug 4;12(5):864-78. doi: 10.1016/j.celrep.2015.06.063. Epub 2015 Jul 23.

Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry.

Author information

1
Insitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30165 Hannover, Germany; Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, the Rockefeller University, New York, NY 10065, USA. Electronic address: gisa.gerold@twincore.de.
2
Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, 82152 Martinsried, Germany.
3
Insitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30165 Hannover, Germany.
4
Inserm Unit 1110, Université de Strasbourg, Strasbourg 67000, France.
5
Department of General, Visceral and Transplant Surgery, Hannover Medical School, 30165 Hannover, Germany.
6
Institute for Medical Informatics and Biometry (IMB), Medical School, University of Technology Dresden, 01307 Dresden, Germany.
7
Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
8
Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, the Rockefeller University, New York, NY 10065, USA.
9
Insitute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30165 Hannover, Germany. Electronic address: thomas.pietschmann@twincore.de.

Abstract

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.

Comment in

PMID:
26212323
PMCID:
PMC4836839
DOI:
10.1016/j.celrep.2015.06.063
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center