title: The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2.
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.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore.
authors.forename: Jude Juventus
authors.initials: JJ
authors.lastname: Aweya
authors.forename: Tze Minn
authors.initials: TM
authors.lastname: Mak
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
authors.forename: Yee-Joo
authors.initials: YJ
authors.lastname: Tan
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000071186:Beclin-1; D053148:Caspase 3 / Q000096:biosynthesis; D016923:Cell Death / Q000187:drug effects*; D016174:Hepacivirus / Q000472:pathogenicity*; D022781:Hepatocytes / Q000502:physiology / Q000821:virology; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D011485:Protein Binding; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D053148:Caspase 3; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D037521:Virulence Factors; C491997:BECN1 protein, human; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C477012:MAP1LC3A protein, human; C088369:p7 protein, Hepatitis C virus; C499320:PARP1 protein, human