INHIBITION OF TUMOR-NECROSIS-FACTOR (TNF-ALPHA)-MEDIATED APOPTOSIS BYHEPATITIS-C VIRUS CORE PROTEIN

Hepatitis C virus (HCV) putative core protein has displayed many intri guing biological properties, Since tumor necrosis factor (TNF) plays a n important role in controlling viral infection, in this study the eff ect of the core protein was investigated on the TNF-alpha induced apop tosis of human breast carcinoma cells (MCF7). RCV core protein when ex pressed inhibited TNF-alpha-induced apoptotic cell death unlike the co ntrol MCF7 cells, as determined by cell viability and DNA fragmentatio n analysis. Additionally, HCV core protein blocked the TNF-induced pro teolytic cleavage of the death substrate poly(ADP-ribose) polymerase f rom its native 116-kDa protein to the characteristic 85-kDa polypeptid e, Results from this study suggest that the HCV core protein plays a r ole in the inhibition of TNF-alpha-mediated cell death. Thus, the abil ity of core protein to inhibit the TNF-mediated apoptotic signaling pa thway may provide a selective advantage for HCV replication, allowing for evasion of host antiviral defense mechanisms.