title: Hepatitis C virus RNA replication requires a conserved structural motif within the transmembrane domain of the NS5B RNA-dependent RNA polymerase.
abstract: Hepatitis C virus (HCV) nonstructural protein 5B (NS5B), the viral RNA-dependent RNA polymerase (RdRp), is a tail-anchored protein with a highly conserved C-terminal transmembrane domain (TMD) that is required for the assembly of a functional replication complex. Here, we report that the TMD of the HCV RdRp can be functionally replaced by a newly identified analogous membrane anchor of the GB virus B (GBV-B) NS5B RdRp. Replicons with a chimeric RdRp consisting of the HCV catalytic domain and the GBV-B membrane anchor replicated with reduced efficiency. Compensatory amino acid changes at defined positions within the TMD improved the replication efficiency of these chimeras. These observations highlight a conserved structural motif within the TMD of the HCV NS5B RdRp that is required for RNA replication.
authors.affiliation: Department of Medicine II, University of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany. Volker.Brass@uniklinik-freiburg.de
authors.forename: Volker
authors.initials: V
authors.lastname: Brass
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gouttenoire
authors.forename: Anja
authors.initials: A
authors.lastname: Wahl
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Pal
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
authors.forename: François
authors.initials: F
authors.lastname: Penin
authors.forename: Darius
authors.initials: D
authors.lastname: Moradpour
mesh_terms: D019943:Amino Acid Substitution; D017124:Conserved Sequence; D016174:Hepacivirus / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000096:biosynthesis*; D012324:RNA-Dependent RNA Polymerase; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase