Hepatitis B virus core protein interacts with CD59 to promote complement-mediated liver inflammation during chronic hepatitis B virus infection

FEBS Lett. 2013 Oct 11;587(20):3314-20. doi: 10.1016/j.febslet.2013.08.044. Epub 2013 Sep 10.

Abstract

The inflammatory response mediated by the immune system is the major cause of hepatitis B virus (HBV)-associated liver injury. Here, we identified CD59, as a novel HBc-interacting protein in hepatocytes by tandem affinity purification (TAP) screening. The expression of CD59 was markedly down-regulated in HBc-transfected HepG2 or HepG2.215 cells, which resulted in an upshift of hepatocyte sensitivity to membrane attack complex (MAC)-induced cell lysis. These results were consistent with the accumulation of MACs in the liver of HBV-infected patients. Additional analyses using laser confocal microscopy, quantitative PCR and flow cytometry revealed that CD59 was specifically translocated to the nucleus upon binding to HBc, which induced the down-regulation of CD59 on both the mRNA and protein levels.

Keywords: CD59; Complement; HBV; HBc; Inflammation; MAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • CD59 Antigens / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Hep G2 Cells
  • Hepatitis B virus / genetics
  • Hepatitis B virus / metabolism*
  • Hepatitis B virus / pathogenicity*
  • Hepatitis, Chronic / genetics
  • Hepatitis, Chronic / metabolism*
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Microscopy, Confocal
  • Viral Structural Proteins / genetics
  • Viral Structural Proteins / metabolism*

Substances

  • CD59 Antigens
  • Viral Structural Proteins