title: NS5B induces up-regulation of the BH3-only protein, BIK, essential for the hepatitis C virus RNA replication and viral release.
abstract: Hepatitis C virus (HCV) induces cytopathic effects in the form of hepatocytes apoptosis thought to be resulted from the interaction between viral proteins and host factors. Using pathway specific PCR array, we identified 9 apoptosis-related genes that are dysregulated during HCV infection, of which the BH3-only pro-apoptotic Bcl-2 family protein, BIK, was consistently up-regulated at the mRNA and protein levels. Depletion of BIK protected host cells from HCV-induced caspase-3/7 activation but not the inhibitory effect of HCV on cell viability. Furthermore, viral RNA replication and release were significantly suppressed in BIK-depleted cells and over-expression of the RNA-dependent RNA polymerase, NS5B, was able to induce BIK expression. Immunofluorescence and co-immunoprecipitation assays showed co-localization and interaction of BIK and NS5B, suggesting that BIK may be interacting with the HCV replication complex through NS5B. These results imply that BIK is essential for HCV replication and that NS5B is able to induce BIK expression.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore.
authors.forename: Jude Juventus
authors.initials: JJ
authors.lastname: Aweya
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore.
authors.forename: Ching Wooen
authors.initials: CW
authors.lastname: Sze
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A⁎STAR), Singapore 138673, Singapore.
authors.forename: Anthony
authors.initials: A
authors.lastname: Bayega
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A⁎STAR), Singapore 138673, Singapore.
authors.forename: Nur Khairiah
authors.initials: NK
authors.lastname: Mohd-Ismail
authors.affiliation: Division of Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Lin
authors.initials: L
authors.lastname: Deng
authors.affiliation: Division of Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Hak
authors.initials: H
authors.lastname: Hotta
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A⁎STAR), Singapore 138673, Singapore. Electronic address: yee_joo_tan@nuhs.edu.sg.
authors.forename: Yee-Joo
authors.initials: YJ
authors.lastname: Tan
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis; D015854:Up-Regulation; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology*; D057074:Virus Release / Q000502:physiology; D014779:Virus Replication / Q000502:physiology; D012324:RNA-Dependent RNA Polymerase
chemical_list: D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C096820:BIK protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: BIK; Hepatitis C virus (HCV); NS5B