title: Identification of a lipid kinase as a host factor involved in hepatitis C virus RNA replication.
abstract: A functional screen of an adenovirus-delivered shRNA library that targets approximately 4500 host genes was performed to identify cellular factors that regulate hepatitis C virus (HCV) sub-genomic RNA replication. Seventy-three hits were further examined by siRNA oligonucleotide-directed knockdown, and silencing of the PI4KA gene was demonstrated to have a significant effect on the replication of a HCV genotype 1b replicon. Using transient siRNA oligonucleotide transfections and stable shRNA knockdown clones in HuH-7 cells, the PI4KA gene was shown to be essential for the replication of all HCV genotypes tested (1a, 1b and 2a) but not required for bovine viral diarrhea virus (BVDV) RNA replication.
authors.affiliation: Boehringer Ingelheim (Canada) Ltd, 2100 Cunard St., Laval, QC, Canada H7S 2G5. frederic.vaillancourt@boehringer-ingelheim.com
authors.forename: Frédéric H
authors.initials: FH
authors.lastname: Vaillancourt
authors.forename: Louise
authors.initials: L
authors.lastname: Pilote
authors.forename: Mireille
authors.initials: M
authors.lastname: Cartier
authors.forename: Julie
authors.initials: J
authors.lastname: Lippens
authors.forename: Michel
authors.initials: M
authors.lastname: Liuzzi
authors.forename: Richard C
authors.initials: RC
authors.lastname: Bethell
authors.forename: Michael G
authors.initials: MG
authors.lastname: Cordingley
authors.forename: George
authors.initials: G
authors.lastname: Kukolj
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D015723:Gene Library; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D006526:Hepatitis C / Q000201:enzymology*; D006801:Humans; D015778:Minor Histocompatibility Antigens; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics*; D015203:Reproducibility of Results; D014779:Virus Replication / Q000235:genetics*
chemical_list: D015778:Minor Histocompatibility Antigens; D034741:RNA, Small Interfering; D012367:RNA, Viral; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase