A Genetic Interaction between Hepatitis C Virus NS4B and NS3 Is Important for RNA Replication

A genetic interaction between hepatitis C virus NS4B and NS3 is important for RNA replication.

Hepatitis C virus (HCV) nonstructural protein 4B (NS4B), a poorly characterized integral membrane protein, is thought to function as a scaffold for replication complex assembly; however, functional interactions with the other HCV nonstructural proteins within this complex have not been defined. We report that a Con1 chimeric subgenomic replicon containing the NS4B gene from the closely related ...

A nucleotide binding motif in hepatitis C virus (HCV) NS4B mediates HCV RNA replication.

Hepatitis C virus (HCV) is a major cause of viral hepatitis. There is no effective therapy for most patients. We have identified a nucleotide binding motif (NBM) in one of the virus's nonstructural proteins, NS4B. This structural motif binds and hydrolyzes GTP and is conserved across HCV isolates. Genetically disrupting the NBM impairs GTP binding and hydrolysis and dramatically inhibits HCV RN...

NS4B self-interaction through conserved C-terminal elements is required for the establishment of functional hepatitis C virus replication complexes.

Hepatitis C virus (HCV) is an important human pathogen, persistently infecting more than 170 million individuals worldwide. Studies of the HCV life cycle have become possible with the development of cell culture systems supporting the replication of viral RNA and the production of infectious virus. However, the exact functions of individual proteins, especially of nonstructural protein 4B (NS4B...

Modulation of the hepatitis C virus RNA-dependent RNA polymerase activity by the NS3 helicase and the NS4B membrane protein

DDB1 is a cellular substrate of NS3/4A protease and required for hepatitis C virus replication.

Hepatitis C virus (HCV) infection often causes long-term persistent hepatitis, which eventually leads to liver cirrhosis and hepatocellular carcinoma. HCV-encoded NS3/4A protease plays an important role in HCV immune evasion by cleaving key adapter proteins VISA and TRIF of the RIG-I-like receptors and Toll-like receptors mediated interferon (IFN) induction pathways. To further understand the r...