Hepatitis C virus NS5A protein protects against TNF-α mediated apoptotic cell death

• Published in: Virus research 2000-04, Vol.67 (2), p.173-178
• Main Authors: Ghosh, Asish K, Majumder, Mainak, Steele, Robert, Meyer, Keith, Ray, Ranjit, Ray, Ratna B
• Format: Article
• Language: English
• Subjects: Apoptosis; Blotting, Western; Caspase 3; Caspases - analysis; Caspases - metabolism; Cell Death - drug effects; Cell Line; Dose-Response Relationship, Drug; Hepacivirus - chemistry; Hepatitis C virus; HepG2 cells; Humans; Microscopy, Confocal; NS5A protein; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Proteins - analysis; Proteins - metabolism; Recombinant Proteins - biosynthesis; Time Factors; TNF-α; Transfection; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - pharmacology; Viral Nonstructural Proteins - biosynthesis; Viral Nonstructural Proteins - pharmacology; Viral Nonstructural Proteins - physiology
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/S0168-1702(00)00141-6

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-α induced apoptotic cell death. HepG2 cells expressing NS5A exhibited an inhibitory role in relation to TNF-α 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-α induced cells. Together, these results suggest that HCV NS5A protein protects against TNF-α mediated apoptotic cell death.