title: Cell culture-adaptive NS3 mutations required for the robust replication of genome-length hepatitis C virus RNA.
abstract: We recently established a genome-length HCV RNA-replicating cell line (O strain of genotype 1b; here called O cells) using cured cells derived from sO cells, in which HCV subgenomic replicon RNA with an adaptive NS5A mutation (S2200R) is replicated. Characterization of the O cells revealed a second adaptive NS3 mutation (K1609E) required for genome-length HCV RNA replication. To clarify the role of adaptive mutation in genome-length HCV RNA replication, we newly established one and three kinds of genome-length HCV RNA-replicating cell lines possessing the cell background of sO and O cells, respectively, and found additional adaptive NS3 mutations (Q1112R, P1115L, and E1202G) required for the robust replication of genome-length HCV RNA. We further found that specific combinations of adaptive NS3 mutations drastically enhanced HCV RNA replication, regardless of the cell lines examined. These findings suggest that specific viral factors may affect the replication level of genome-length HCV RNA.
authors.affiliation: Department of Molecular Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Abe
authors.forename: Masanori
authors.initials: M
authors.lastname: Ikeda
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Dansako
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Naka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology; D018929:Cell Culture Techniques; D016679:Genome, Viral; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D012367:RNA, Viral / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics* / Q000502:physiology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases