Host cell kinases and the hepatitis C virus life cycle

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Hepacivirus / genetics*
  • Hepacivirus / pathogenicity
  • Hepatitis C / genetics*
  • Hepatitis C / virology
  • Hepatocytes / enzymology
  • Hepatocytes / virology
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Life Cycle Stages / genetics
  • Minor Histocompatibility Antigens
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Receptor, EphA2 / genetics
  • Viral Nonstructural Proteins / genetics
  • Virus Assembly / genetics
  • Virus Internalization

Substances

  • Minor Histocompatibility Antigens
  • NS-5 protein, hepatitis C virus
  • Viral Nonstructural Proteins
  • Phosphotransferases (Alcohol Group Acceptor)
  • phosphatidylinositol phosphate 4-kinase
  • EGFR protein, human
  • ErbB Receptors
  • Receptor, EphA2