Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry
Open accessAbstract
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.
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In HCV-infected hepatoma cells, CD81 interacts with serum response factor binding protein 1, which is critical for HCV cell penetration and is a specific entry factor for all seven HCV genotypes.
“Serum response factor binding protein 1 was identified as a CD81 interaction, and shown to have a critical role in the cell penetration by HCV. This protein was further demonstrated to be a specific virus entry factor for HCV, functioning for all seven HCV genotypes.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [32]
A more precise comparison of the bait and control IPs can be provided by relative quantification using metabolic labeling with stable isotopes.
“Alternatively, a more precise comparison of the bait and control IPs can be provided by relative quantification using metabolic labeling with stable isotopes [31,32]”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [32]
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Lum, K. K., & Cristea, I. M. (2016) · Expert Review of Proteomics · doi:10.1586/14789450.2016.1147353 · Cited by 113 · see citing works
- Authors
- Gerold, G., Meissner, F., Bruening, J., Welsch, K., Perin, P. M., Baumert, T. F., Vondran, F. W., Kaderali, L., Marcotrigiano, J., Khan, A. G., Mann, M., Rice, C. M., & Pietschmann, T.
- Affiliations
- Helmholtz Centre for Infection Research (DE)
- Max Planck Institute of Biochemistry (DE)
- Inserm (FR)
- Medizinische Hochschule Hannover (DE)
- Technische Universität Dresden (DE)
- Rutgers, The State University of New Jersey (US)
- Rockefeller University (US)
- Corresponding author
- Gerold, Gisa
- Pietschmann, Thomas
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 12
- Issue
- 5
- Pages
- 864-878
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4836839
- OpenAlex
- W1727851421
- Cited by
- 60
- References
- 57
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 3 · 2016: 12 · 2015: 2
- FWCI
- 5.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Greenberg Medical Research Institute
- Starr Foundation
- Deutsche Forschungsgemeinschaft (SFB 900, GE 2145/3-1)
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI072613)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Virus Research Studies
- Keywords
- hepatitis C virus, viral entry, CD81, host factors, host-virus interaction, protein-protein interaction, hepatocytes, HCV genotypes, quantitative proteomics, RNA interference
- MeSH terms
- Humans, Transcription Factors, Hepacivirus, Proteomics, Cell Line, Tumor, Virus Internalization
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