title: Chaperonin TRiC/CCT participates in replication of hepatitis C virus genome via interaction with the viral NS5B protein.
abstract: To identify the host factors implicated in the regulation of hepatitis C virus (HCV) genome replication, we performed comparative proteome analyses of HCV replication complex (RC)-rich membrane fractions prepared from cells harboring genome-length bicistronic HCV RNA at the exponential and stationary growth phases. We found that the eukaryotic chaperonin T-complex polypeptide 1 (TCP1)-ring complex/chaperonin-containing TCP1 (TRiC/CCT) plays a role in the replication possibly through an interaction between subunit CCT5 and the viral RNA polymerase NS5B. siRNA-mediated knockdown of CCT5 suppressed RNA replication and production of the infectious virus. Gain-of-function activity was shown following co-transfection with whole eight TRiC/CCT subunits. HCV RNA synthesis was inhibited by an anti-CCT5 antibody in a cell-free assay. These suggest that recruitment of the chaperonin by the viral nonstructural proteins to the RC, which potentially facilitate folding of the RC component(s) into the mature active form, may be important for efficient replication of the HCV genome.
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Hideki
authors.initials: H
authors.lastname: Aizaki
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Hara
authors.forename: Mami
authors.initials: M
authors.lastname: Matsuda
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ando
authors.forename: Tetsu
authors.initials: T
authors.lastname: Shimoji
authors.forename: Kyoko
authors.initials: K
authors.lastname: Murakami
authors.forename: Takahiro
authors.initials: T
authors.lastname: Masaki
authors.forename: Ikuo
authors.initials: I
authors.lastname: Shoji
authors.forename: Sakae
authors.initials: S
authors.lastname: Homma
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Miyamura
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D045744:Cell Line, Tumor; D018833:Chaperonins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D018833:Chaperonins; D012367:RNA, Viral; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C069130:nucleocapsid protein, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase