Apolipoprotein E on hepatitis C virion facilitates infection through interaction with low-density lipoprotein receptor

David M. Owen, Hua Huang, Jin Ye, Michael Gale

Research output: Contribution to journalArticle

167 Scopus citations

Abstract

Hepatitis C virus (HCV) infection is a major cause of liver disease. HCV associates with host apolipoproteins and enters hepatocytes through complex processes involving some combination of CD81, claudin-1, occludin, and scavenger receptor BI. Here we show that infectious HCV resembles very low density lipoprotein (VLDL) and that entry involves co-receptor function of the low-density lipoprotein receptor (LDL-R). Blocking experiments demonstrate that β-VLDL itself or anti-apolipoprotein E (apoE) antibody can block HCV entry. Knockdown of the LDL-R by treatment with 25-hydroxycholesterol or siRNA ablated ligand uptake and reduced HCV infection of cells, whereas infection was rescued upon cell ectopic LDL-R expression. Analyses of gradient-fractionated HCV demonstrate that apoE is associated with HCV virions exhibiting peak infectivity and dependence upon the LDL-R for cell entry. Our results define the LDL-R as a cooperative HCV co-receptor that supports viral entry and infectivity through interaction with apoE ligand present in an infectious HCV/lipoprotein complex comprising the virion. Disruption of HCV/LDL-R interactions by altering lipoprotein metabolism may therefore represent a focus for future therapy.

Original languageEnglish (US)
Pages (from-to)99-108
Number of pages10
JournalVirology
Volume394
Issue number1
DOIs
StatePublished - Nov 10 2009

Keywords

  • ApoB
  • ApoE
  • Entry
  • HCV
  • Hepatitis
  • LDL-R
  • Lipoprotein
  • Receptor

ASJC Scopus subject areas

  • Virology

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