title: Hepatitis C virus expression and interferon antiviral action is dependent on PKR expression.
abstract: Interferon (IFN)-inducible double-stranded RNA-activated protein kinase (PKR) is thought to play a key antiviral role against hepatitis C virus (HCV). However, demonstrating the importance of PKR expression on HCV protein synthesis in the presence or absence of IFN has proven difficult in vivo. In the present experiment, full-length HCV constructs were transiently transfected into two cell lines stably expressing T7 RNA polymerase. HCV expression was monitored under conditions of upregulated or downregulated PKR expression. In addition, IFN was monitored during downregulation of PKR. HCV expression effectively increased PKR expression, as well as that of its regulated proteins. PKR was obviously knocked down by PKR-specific siRNA, which resulted in significantly increased HCV core protein levels. Conversely, over-expression of PKR significantly suppressed HCV core levels in both cell lines. Furthermore, IFN induced high levels of PKR, whereas downregulation of PKR reversed IFN's antiviral effects and increased HCV core levels. Based on these results, it appears that HCV protein expression is directly dependent on PKR expression. PKR is antiviral toward HCV and responsible for IFN's effect against HCV.
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tokumoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hiasa
authors.forename: Norio
authors.initials: N
authors.lastname: Horiike
authors.forename: Kojiro
authors.initials: K
authors.lastname: Michitaka
authors.forename: Bunzo
authors.initials: B
authors.lastname: Matsuura
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.forename: Morikazu
authors.initials: M
authors.lastname: Onji
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D007372:Interferons; D011494:Protein Kinases