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Published on: April 17, 2017
Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus
Gisa Gerold1, Felix Meissner2, Janina Bruening3
1Insitute 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.
Researchers identified serum response factor binding protein 1 (SRFBP1) as a key host factor enabling Hepatitis C virus (HCV) entry into liver cells. This discovery highlights SRFBP1
Area of Science:
- Virology
- Cell Biology
- Proteomics
Background:
- Hepatitis C virus (HCV) entry into hepatocytes involves host proteins, notably CD81.
- The precise role of CD81 in HCV entry and its subsequent protein interactions are not well understood.
Purpose of the Study:
- To identify host proteins interacting with CD81 following HCV binding.
- To characterize the function of these interacting proteins in HCV entry.
Main Methods:
- Development of a quantitative proteomics protocol to detect CD81-HCV interactions.
- RNA interference (RNAi) screening to assess the role of identified binding partners in infection.
- Detailed characterization of serum response factor binding protein 1 (SRFBP1) function.
Main Results:
- Identified 26 dynamic binding partners of CD81 triggered by HCV.
- Six identified proteins were confirmed to promote HCV infection via RNAi.
- SRFBP1 was recruited to CD81 during HCV uptake and supports infection across all seven HCV genotypes.
- SRFBP1 facilitates entry of HCV but not other viruses like vesicular stomatitis virus or human coronavirus.
Conclusions:
- SRFBP1 is an HCV-specific, pan-genotypic host entry factor.
- Quantitative proteomics is effective for studying pathogen entry mechanisms.
- Host protein-protein interactions are crucial for HCV invasion.
