Phospholipid scramblase 1 mediates hepatitis C virus entry into host cells

FEBS Lett. 2011 Sep 2;585(17):2647-52. doi: 10.1016/j.febslet.2011.07.019. Epub 2011 Jul 28.

Abstract

Hepatitis C virus (HCV) infects human hepatocytes through several host factors. However, other prerequisite factors for viral entry remain to be identified. Using a yeast two-hybrid screen, we found that human phospholipid scramblase 1 interacts with HCV envelope proteins E1 and E2. These physical interactions were confirmed by co-immunoprecipitation and GST pull-down assays. Knocking down the expression of PLSCR1 inhibited the entry of HCV pseudoparticles. Moreover, PLSCR1 was required for the initial attachment of HCV onto hepatoma cells, where it specifically interacted with entry factor OCLN. We show that PLSCR1 is a novel attachment factor for HCV entry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Cell Line, Tumor
  • Claudin-1
  • Hepacivirus / metabolism*
  • Hepacivirus / physiology
  • Humans
  • Immunoprecipitation
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Occludin
  • Phospholipid Transfer Proteins / genetics
  • Phospholipid Transfer Proteins / metabolism*
  • Polymerase Chain Reaction
  • Protein Binding
  • RNA Interference
  • Scavenger Receptors, Class B / genetics
  • Scavenger Receptors, Class B / metabolism
  • Tetraspanin 28
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism

Substances

  • Antigens, CD
  • CD81 protein, human
  • CLDN1 protein, human
  • Claudin-1
  • E1 protein, Hepatitis C virus
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • PLSCR1 protein, human
  • Phospholipid Transfer Proteins
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • Tetraspanin 28
  • Viral Envelope Proteins
  • glycoprotein E2, Hepatitis C virus