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Biochim Biophys Acta. 2015 Oct;1854(10 Pt B):1657-62. doi: 10.1016/j.bbapap.2015.04.011. Epub 2015 Apr 18.

Host cell kinases and the hepatitis C virus life cycle.

Author information

1
Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France.
2
Department of Microbiology, School of Biomedical Sciences, Monash University, Victoria, Australia.
3
Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Electronic address: thomas.baumert@unistra.fr.

Abstract

Hepatitis C virus (HCV) infection relies on virus-host interactions with human hepatocytes, a context in which host cell kinases play critical roles in every step of the HCV life cycle. During viral entry, cellular kinases, including EGFR, EphA2 and PKA, regulate the localization of host HCV entry factors and induce receptor complex assembly. Following virion internalization, viral genomes replicate on endoplasmic reticulum-derived membranous webs. The formation of membranous webs depends on interactions between the HCV NS5a protein and PI4KIIIα. The phosphorylation status of NS5a, regulated by PI4KIIIα, CKI and other kinases, also acts as a molecular switch to virion assembly, which takes place on lipid droplets. The formation of lipid droplets is enhanced by HCV activation of IKKα. In view of the multiple crucial steps in the viral life cycle that are mediated by host cell kinases, these enzymes also represent complementary targets for antiviral therapy. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.

KEYWORDS:

Hepatitis C virus; Host cell kinases; Virus–host interactions

PMID:
25896387
DOI:
10.1016/j.bbapap.2015.04.011
[Indexed for MEDLINE]

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