TY - JOUR
T1 - Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase
AU - Watashi, Koichi
AU - Ishii, Naoto
AU - Hijikata, Makoto
AU - Inoue, Daisuke
AU - Murata, Takayuki
AU - Miyanari, Yusuke
AU - Shimotohno, Kunitada
N1 - Funding Information:
We are grateful to Dr. Takamizawa at Osaka University for an anti-NS5A antibody, Dr. Kohara at Tokyo Metropolitan Institute of Medical Science for an anti-NS5B antibody, and Dr. Adachi at the Institute of Health Biosciences, the University of Tokushima for an expression plasmid for HIV-1 Gag. We also appreciate Novartis (Basel, Switzerland) for providing CsA derivatives and sanglifehrins. This work was supported by grants in aid for cancer research and for the second-term comprehensive 10 year strategy for cancer control from the Ministry of Health, Labor, and Welfare; through grants in aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology; by grants in aid for Research for the Future from the Japanese Society for the Promotion of Science; and by the Program for Promotion of Fundamental Studies in Health Science of the Organization for Pharmaceutical Safety and Research (OPSR) of Japan.
PY - 2005/7/1
Y1 - 2005/7/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/21244433445
UR - https://www.scopus.com/pages/publications/21244433445#tab=citedBy
U2 - 10.1016/j.molcel.2005.05.014
DO - 10.1016/j.molcel.2005.05.014
M3 - Article
C2 - 15989969
AN - SCOPUS:21244433445
SN - 1097-2765
VL - 19
SP - 111
EP - 122
JO - Molecular Cell
JF - Molecular Cell
IS - 1
ER -
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