期刊
HEPATOLOGY
卷 51, 期 1, 页码 43-53出版社
WILEY
DOI: 10.1002/hep.23278
关键词
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资金
- Inserm, France, the European Union [LSHM-CT-2004-503359, ERC-2008-AdG-233130-HEPCENT]
- Agence Nationale de la Recherche [ANR-05-CEXC-008]
- Agence Nationale de la Recherche sur le SIDA et les Hepatites Virales [ANRS-06221, 2008/354]
- FRM-BNP Paribas Foundation, Paris, France
- University of Strasbourg, France
- Else-Kroner-Fresenius Foundation, Bad Homburg, Germany [P17/07//A83/06]
- MRC [MC_U130184143] Funding Source: UKRI
- Medical Research Council [MC_U130184143] Funding Source: researchfish
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI070769] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R21DK079293] Funding Source: NIH RePORTER
Chronic hepatitis C virus (HCV) infection is a major cause of liver disease worldwide. Restriction of HCV infection to human hepatocytes suggests that liver-specific host factors play a role in the viral life cycle. Using a yeast-two-hybrid system, we identified apolipoprotein E (apoE) as a liver-derived host factor specifically interacting with HCV nonstructural. protein 5A (NS5A) but not with other viral proteins. The relevance of apoE-NS5A interaction for viral infection was confirmed by co-immunoprecipitation and co-localization studies of apoE and NS5A in an infectious HCV cell culture model system. Silencing apoE expression resulted in marked inhibition of infectious particle production without affecting viral entry and replication. Analysis of particle production in liver-derived cells with silenced apoE expression showed impairment of infectious particle assembly and release. The functional relevance of the apoE-NS5A interaction for production of viral particles was supported by loss or decrease of apoE-NS5A binding in assembly-defective viral mutants. Conclusion: These results suggest that recruitment of apoE by NS5A is important for viral assembly and release of infectious viral particles. These findings have important implications for understanding the HCV life cycle and the development of novel antiviral strategies targeting HCV-lipoprotein interaction. (HEPATOLOGY 2010;51:43-53.)
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