Golgi protein 73 facilitates the interaction of hepatitis C virus NS5A with apolipoprotein E to promote viral particle secretion

Biochem Biophys Res Commun. 2016 Oct 28;479(4):683-689. doi: 10.1016/j.bbrc.2016.09.152. Epub 2016 Sep 30.

Abstract

Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver diseases and hepatocellular carcinoma (HCC). Golgi protein 73 (GP73), a resident Golgi membrane protein, is a novel serum biomarker for the diagnosis of liver diseases and HCC. Although previous studies have demonstrated that HCV upregulates GP73 expression and GP73 promotes HCV secretion through its interaction with apolipoprotein E (ApoE), the exact mechanism underlying GP73 regulates HCV secretion remains unclear. In this study, we demonstrated that GP73 mediates the interaction of ApoE with HCV NS5A protein to promote HCV secretion. We revealed that GP73 is colocalized with HCV replication complex in infected-Huh7.5.1 cells. Further studies demonstrated that GP73 interacted with both NS5A and ApoE proteins. Furthermore, knockdown of GP73 significantly reduced the binding of NS5A with ApoE, and the production of virus particles in culture supernatant. Taken together, our studies revealed that GP73 promotes HCV secretion by directly mediating the interaction of ApoE with HCV replication complex through binding with HCV NS5A.

Keywords: ApoE; Apolipoprotein E; GP73; Golgi protein 73; HCC; HCV; HCV particle assembly and secretion; Hepatitis C virus; Hepatocellular carcinoma; NS5A; Nonstructural protein 5A.

MeSH terms

  • Apolipoproteins E / metabolism*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / virology
  • HEK293 Cells
  • HeLa Cells
  • Hepacivirus / physiology*
  • Hepatitis C / metabolism
  • Hepatitis C / virology
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / virology
  • Membrane Proteins / metabolism*
  • Viral Nonstructural Proteins / metabolism*
  • Virion / physiology*
  • Virus Assembly
  • Virus Release*

Substances

  • ApoE protein, human
  • Apolipoproteins E
  • GOLM1 protein, human
  • Membrane Proteins
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus