The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2

Virus Res. 2013 Mar;172(1-2):24-34. doi: 10.1016/j.virusres.2012.12.005. Epub 2012 Dec 12.

Abstract

Most viruses encode proteins that modulate cell-death signaling by the host. For hepatitis C virus (HCV) infection, apoptosis and other forms of cell-death have been observed in vitro and in vivo but the detailed understanding of this intricate viral-host interplay is unclear. This study examined the role played by the HCV p7 protein in the induction of cell-death. By measuring caspase-3/7 activation and cleavage of endogenous PARP, two hallmarks of apoptosis, the overexpression of p7 protein was shown to induce apoptosis in Huh7.5 cells. Furthermore, p7-induced apoptosis is caspase-dependent and involves both the intrinsic and extrinsic pathways. Similar to the M2 protein of influenza A virus, p7-induced apoptosis is independent of its ion channel activity. Coimmunoprecipitation experiments further showed that both M2 and p7 interact with the essential autophagy protein Beclin-1. However, only the M2 protein could cause an increase in the level of LC3-II, which is an indicator of autophagic activity. Thus, although the p7 protein is functionally similar to the well-characterized M2 protein, they differ in their activation of autophagic cell-death. Taken together, these results shed more light on the relationship between the HCV p7 ion channel protein and cell-death induction in host cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism
  • Beclin-1
  • Caspase 3 / biosynthesis
  • Cell Death / drug effects*
  • Hepacivirus / pathogenicity*
  • Hepatocytes / physiology
  • Hepatocytes / virology
  • Humans
  • Influenza A virus / pathogenicity
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / biosynthesis
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / biosynthesis
  • Protein Binding
  • Up-Regulation
  • Viral Matrix Proteins / metabolism
  • Viral Proteins / metabolism*
  • Virulence Factors / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • M2 protein, Influenza A virus
  • MAP1LC3A protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Viral Matrix Proteins
  • Viral Proteins
  • Virulence Factors
  • p7 protein, Hepatitis C virus
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Caspase 3