Apolipoprotein E interacts with hepatitis C virus nonstructural protein 5A and determines assembly of infectious particles.

Wagane Benga 1, 2 Sophie Krieger 1, 2 Maria Dimitrova 1, 2 Mirjam Zeisel 1, 2 Marie Parnot 1, 2 Joachim Lupberger 1, 2 Eberhard Hildt 3 Guangxiang Luo 4 John Mclauchlan 5 Thomas Baumert 1, 2, 6, * Catherine Schuster 1, 2, *
* Auteur correspondant
1 Interaction virus-hôte et maladies du foie
2 Institut de Virologie
3 Molekulare Medizinische Virologie
4 Department of Microbiology, Immunology and Molecular Genetics
5 Virology Unit
6 Service d'Hépato-gastroentérologie
Abstract : 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.
Keywords : infection liver lipid metabolism virus-host interactions treatment
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Article dans une revue
Hepatology, Wiley-Blackwell, 2010, 51 (1), pp.43-53. 〈10.1002/hep.23278〉
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http://www.hal.inserm.fr/inserm-00705655
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Soumis le : vendredi 8 juin 2012 - 09:52:25
Dernière modification le : jeudi 21 décembre 2017 - 01:04:22
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Wagane Benga, Sophie Krieger, Maria Dimitrova, Mirjam Zeisel, Marie Parnot, et al.. Apolipoprotein E interacts with hepatitis C virus nonstructural protein 5A and determines assembly of infectious particles.. Hepatology, Wiley-Blackwell, 2010, 51 (1), pp.43-53. 〈10.1002/hep.23278〉. 〈inserm-00705655〉

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