title: In-depth phylogenetic analysis of hepatitis C virus subtype 1a and occurrence of 80K and associated polymorphisms in the NS3 protease.
abstract: HCV genetic diversity is high and impacts disease progression, treatment and drug resistance. HCV subtype 1a is divided in two clades (I and II), and the 80 K natural polymorphism in the viral NS3 protease is prevalent in clade I. Paradoxically, countries dominated by this clade have contrasting frequencies of 80 K. Over 2,000 HCV 1a NS3 sequences were retrieved from public databases representing Europe, Oceania and the Americas. Sequences were aligned with HCV reference sequences and subjected to phylogenetic analysis to investigate the relative presence of different subtype 1a clades and NS3 protease mutations. HCV-1a sequences split into clades I and II. Clade I was further structured into three subclades, IA to C. Sub-clade IA prevailed in the U.S., while subclade IC was major in Brazil. The NS3 80 K polymorphism was associated with subclade IA, but nearly absent in subclades IB and IC, a pattern similarly seen for the 91S/T compensatory mutation. Three HCV-1a-I sub-clades have been identified, with different frequencies in distinct regions. The 80 K and 91A/S mutations were associated with subclade IA, which provide an explanation for the disparities seen in simeprevir resistance profiles of countries dominated by HCV 1a-I, like the U.S. and Brazil.
authors.affiliation: Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Santos
authors.affiliation: Laboratório de AIDS &Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Bello
authors.affiliation: Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luãnna L
authors.initials: LL
authors.lastname: Vidal
authors.affiliation: Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Suiane L
authors.initials: SL
authors.lastname: Souza
authors.affiliation: Laboratório de AIDS &Imunologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Daiana
authors.initials: D
authors.lastname: Mir
authors.affiliation: Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.|Programa de Oncovirologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Soares
mesh_terms: D030561:Databases, Nucleic Acid; D024882:Drug Resistance, Viral / Q000235:genetics*; D016174:Hepacivirus / Q000235:genetics*; D010802:Phylogeny; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases