HCV functional genomics: Protein interactions with NS3 and their role in viral replication

Abstract

The hepatitis C virus nonstructural protein 3 (NS3) is both a protease as well as helicase. NS3 has been implicated to play important roles in the propagation and replication of HCV. Yeast-two hybrid screens for NS3 interacting viral and host proteins, found NS3 to interact with itself and a host protein, LMP7. NS3-NS3 dimerization was found to be important for optimal helicase activity. The binding of NS3 to LMP7, an interferon gamma inducible beta subunit of the proteasome was found to down regulate proteasome activity. This might be a possible route by which the virus evades host immune defenses as proteasomes are involved in the generation of viral antigens for presentation to cytotoxic T cells.