Hepatitis C virus core protein potentiates TNF-alpha-induced NF-kappa B activation through TRAF2-IKK beta-dependent pathway

Previous work has implicated that the core protein of hepatitis C virus (HC V) may play a modulatory effect on NF-kappaB activation induced by TNF-alph a. However, it is unclear how HCV core protein modulates TNF-alpha -induced NK-kappaB activation. Here we show that overexpression of HCV core protein potentiates NF-KB activation induced by TNF-alpha. Expression of dominant negative form of TRAF2 inhibits the synergistic effects of HCV core protein on NF-kappaB activation, suggesting that HCV core protein potentiates NF-k appaB activation through TRAF2. Moreover, we demonstrate that HCV core prot ein potentiates TRAF2-mediated NF-kappaB activation via IKK beta. In additi on, HCV core protein associates with TNF-R1-TRADD-TRAF2 signaling complex, resulting in synergistically activation of NF-kappaB induced by TNF-alpha. Thus, these observations indicate that HCV core protein may play an importa nt role in the regulation of the cellular inflammatory and immune responses through NF-kappaB. (C) 2001 Academic Press.