title: Hepatitis C virus NS5A protein protects against TNF-alpha mediated apoptotic cell death.
abstract: Hepatitis C virus (HCV) often causes a prolonged and persistent infection which may lead to hepatocellular carcinoma. We have previously reported that the nonstructural 5A (NS5A) protein of HCV promotes cell growth [Ghosh, A.K., Steele, R., Meyer, K., Ray, R., Ray, R.B., 1999. Hepatitis C virus NS5A protein modulates cell cycle regulatory genes and promotes cell growth. J. Gen. Virol. 80, 1179-1183]. In this study, we investigated the role of HCV NS5A (genotype 1a, strain H) in TNF-alpha induced apoptotic cell death. HepG2 cells expressing NS5A exhibited an inhibitory role in relation to TNF-alpha mediated apoptotic cell death. The NS5A protein blocked the activation of caspase-3 and inhibited proteolytic cleavage of the death substrate poly (ADP-ribose) polymerase in TNF-alpha induced cells. Together, these results suggest that HCV NS5A protein protects against TNF-alpha mediated apoptotic cell death.
authors.affiliation: Department of Pathology, Saint Louis University, St. Louis, MO 63104, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: M
authors.initials: M
authors.lastname: Majumder
authors.forename: R
authors.initials: R
authors.lastname: Steele
authors.forename: K
authors.initials: K
authors.lastname: Meyer
authors.forename: R
authors.initials: R
authors.lastname: Ray
authors.forename: R B
authors.initials: RB
authors.lastname: Ray
mesh_terms: D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000737:chemistry*; D006801:Humans; D018613:Microscopy, Confocal; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D053148:Caspase 3; D020169:Caspases; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D017361:Viral Nonstructural Proteins; C499320:PARP1 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C505407:CASP3 protein, human