Hepatitis C virus core protein potentiates TNF-α-induced NF-κB activation through TRAF2-IKKβ-dependent pathway

Previous work has implicated that the core protein of hepatitis C virus (HCV) may play a modulatory effect on NF-κB activation induced by TNF-α. However, it is unclear how HCV core protein modulates TNF-α-induced NK-κB activation. Here we show that overexpression of HCV core protein potentiates NF-κB activation induced by TNF-α. Expression of dominant negative form of TRAF2 inhibits the synergistic effects of HCV core protein on NF-κB activation, suggesting that HCV core protein potentiates NF-κB activation through TRAF2. Moreover, we demonstrate that HCV core protein potentiates TRAF2-mediated NF-κB activation via IKKβ. In addition, HCV core protein associates with TNF-R1-TRADD-TRAF2 signaling complex, resulting in synergistically activation of NF-κB induced by TNF-α. Thus, these observations indicate that HCV core protein may play an important role in the regulation of the cellular inflammatory and immune responses through NF-κB.