Non-structural protein NS4B: HCV replication web inducer

Hepatitis C virus (HCV) genome consists of a positive strand RNA encoding a polyprotein, having 3 structural and 6 non-structural components including non structural protein 4B (NS4B). NS4B is a 27 KDa protein, of 261 amino acids, released after polyprotein cleavage by NS3 serine protease and localized on endoplasmic reticulum (ER). NS4B has 2 alpha helices each in its N and C terminal domains and 4 transmembrane domains in its central region. N-terminal domain resides in the ER-lumen while C-terminal domain resides in the cytoplasm. Around its middle it has a nucleotide binding motif (NBM) which plays a role in ATP and GTP hydrolysis. It is involved in hyperphosphorylation of the NS5A protein and is also thought to be involved in production of various cytokines by the activation of NF-kB pathway. NS4B plays a major role in HCV replication by inducing membranous web and facilitating other HCV proteins necessary for replication. Here we discuss various functional aspects of this protein and their potential for targeted antiviral approaches.