Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase.
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 (HCV) 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.
Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Koichi
K
Watashi
Naoto
N
Ishii
Makoto
M
Hijikata
Daisuke
D
Inoue
Takayuki
T
Murata
Yusuke
Y
Miyanari
Kunitada
K
Shimotohno
D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D021983:Cyclophilins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D034622:RNA Interference; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000502:physiology*; D012093:Replicon; D014779:Virus Replication
D012367:RNA, Viral; C081786:cyclophilin B; D012324:RNA-Dependent RNA Polymerase; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase