title: Peptidyl-prolyl isomerase Pin1 is a cellular factor required for hepatitis C virus propagation.
abstract: The life cycle of hepatitis C virus (HCV) is highly dependent on cellular factors. Using small interfering RNA (siRNA) library screening, we identified peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) as a host factor involved in HCV propagation. Here we demonstrated that silencing of Pin1 expression resulted in decreases in HCV replication in both HCV replicon cells and cell culture-grown HCV (HCVcc)-infected cells, whereas overexpression of Pin1 increased HCV replication. Pin1 interacted with both the NS5A and NS5B proteins. However, Pin1 expression was increased only by the NS5B protein. Both the protein binding and isomerase activities of Pin1 were required for HCV replication. Juglone, a natural inhibitor of Pin1, inhibited HCV propagation by inhibiting the interplay between the Pin1 and HCV NS5A/NS5B proteins. These data indicate that Pin1 modulates HCV propagation and may contribute to HCV-induced liver pathogenesis.
authors.affiliation: National Research Laboratory of Hepatitis C Virus, Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang 431-060, South Korea.
authors.forename: Yun-Sook
authors.initials: YS
authors.lastname: Lim
authors.forename: Huong T L
authors.initials: HT
authors.lastname: Tran
authors.forename: Soo-Je
authors.initials: SJ
authors.lastname: Park
authors.forename: Seung-Ae
authors.initials: SA
authors.lastname: Yim
authors.forename: Soon B
authors.initials: SB
authors.lastname: Hwang
mesh_terms: D002460:Cell Line; D020868:Gene Silencing; D016174:Hepacivirus / Q000254:growth & development*; D054884:Host-Pathogen Interactions; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D025941:Protein Interaction Mapping; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C000606846:PIN1 protein, human