title: Treating hepatitis C: can you teach old dogs new tricks?
abstract: Viruses depend on host-derived factors for their efficient genome replication. Here, we demonstrate that a cellular peptidyl-prolyl cis-trans isomerase (PPIase), cyclophilin B (CyPB), is critical for the efficient replication of the hepatitis C virus genome. CyPB interacted with the HCV RNA polymerase NS5B to directly stimulate its RNA binding activity. Both the RNA interference (RNAi)-mediated reduction of endogenous CyPB expression and the induced loss of NS5B binding to CyPB decreased the levels of HCV replication. Thus, CyPB functions as a stimulatory regulator of NS5B in HCV replication machinery. This regulation mechanism for viral replication identifies CyPB as a target for antiviral therapeutic strategies.
authors.affiliation: Center for the Study of Hepatitis C Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.forename: Shihyun
authors.initials: S
authors.lastname: You
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D021983:Cyclophilins / Q000502:physiology*; D016572:Cyclosporine / Q000378:metabolism / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D019696:Peptidylprolyl Isomerase / Q000502:physiology*; D012367:RNA, Viral / Q000096:biosynthesis; D017361:Viral Nonstructural Proteins / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D021983:Cyclophilins; D016572:Cyclosporine; D019696:Peptidylprolyl Isomerase; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C081786:cyclophilin B; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase