title: Nonstructural 5A protein of hepatitis C virus regulates heat shock protein 72 for its own propagation.
abstract: We identified heat shock protein 72 (Hsp72) as a host factor that was differentially expressed in cells expressing nonstructural 5A (NS5A) protein. To investigate how NS5A modulates Hsp72 in hepatitis C virus (HCV) life cycle, we examined the role of Hsp72 in HCV replication and virus production. NS5A specifically interacted with Hsp72. Both Hsp72 and nuclear factor of activated T cells 5 (NFAT5) levels were increased in cells expressing NS5A protein. Treatments of N-acetylcysteine and glutathione markedly reduced protein levels of both NFAT5 and Hsp72. Knockdown of NFAT5 resulted in decrease in Hsp72 level in cells expressing NS5A. Importantly, silencing of Hsp72 expression resulted in decrease in both RNA replication and virus production in HCV-infected cells. These data indicate that NS5A modulates Hsp72 via NFAT5 and reactive oxygen species activation for HCV propagation.
authors.affiliation: National Research Laboratory of Hepatitis C Virus, Ilsong Institute of Life Science, Hallym University, Anyang, South Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Lim
authors.forename: K S
authors.initials: KS
authors.lastname: Shin
authors.forename: S H
authors.initials: SH
authors.lastname: Oh
authors.forename: S M
authors.initials: SM
authors.lastname: Kang
authors.forename: S J
authors.initials: SJ
authors.lastname: Won
authors.forename: S B
authors.initials: SB
authors.lastname: Hwang
mesh_terms: D002460:Cell Line; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D016174:Hepacivirus / Q000472:pathogenicity*; D022781:Hepatocytes / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
chemical_list: D050884:HSP72 Heat-Shock Proteins; D014157:Transcription Factors; D017361:Viral Nonstructural Proteins; C118125:NFAT5 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase