HCV NS4B

The hepatitis C virus (HCV) non-structural 4B (NS4B) protein is a 27kDa hydrophobic protein which for many years was characterized mainly as a protein of unknown function. Recently, however, information about the protein and its involvement in mediating various viral activities and effects on host cells is beginning to accumulate. NS4B has been implicated in modulation of NS5B's RNA dependent RNA polymerase activity and various host signal transduction pathways, a possible role in HCV carcinogenesis, impairment of ER function, and regulation of both viral and host translation. Perhaps most significant, NS4B has recently been found to be responsible for the formation of a novel intracellular membrane structure, termed the membranous web, which appears to be the platform upon which viral replication occurs. Specific domains within NS4B have been identified which likely underlie the mechanisms employed by NS4B to mediate many of the preceding functions. As such, these domains which include an amphipathic helix and nucleotide-binding motif represent attractive targets for new antiviral strategies.