title: Inter and intra-host variability of hepatitis C virus genotype 1a hypervariable envelope coding domains followed for a 4-11 year of human immunodeficiency virus coinfection and highly active antiretroviral therapy.
abstract: The evolution of hepatitis C virus (HCV) quasispecies in patients with HIV-1 coinfection is not fully understood. The HCV-1a quasispecies heterogeneity was analyzed at inter and intra-host levels along 7.6 years in 21 coinfected patients that showed different virological and immunological responses to highly active antiretroviral therapy (HAART). Two to nine serial samples were subjected to direct and clonal sequence analyses of the envelope glycoprotein 2 (E2) gene. E2-based phylogenies, intra-host HCV evolution and evolutionary rates, as well as dynamics of the quasispecies heterogeneity parameters were evaluated. Bayesian coalescent phylogenies indicated complex evolutionary histories, revealing some viral lineages that persisted along the follow up and others that were detectable at a single or some sampling times, suggesting the occurrence of emergence-extinction cycles. HCV quasispecies underwent very rapid evolution in HAART-treated patients (~3.1 × 10(-2) sub/site/year) following the recovery of the host immunocompetence irrespectively of the virological response to HAART.
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
authors.forename: Mariano
authors.initials: M
authors.lastname: Sede
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Laboratorio de Virología y Genética Molecular, Facultad de Ciencias Naturales sede Trelew, Universidad Nacional de la Patagonia San Juan Bosco, Chubut, Argentina.
authors.forename: Leandro Roberto
authors.initials: LR
authors.lastname: Jones
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires, Argentina.
authors.forename: Franco
authors.initials: F
authors.lastname: Moretti
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Laufer
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. Electronic address: quarleri@fmed.uba.ar.
authors.forename: Jorge
authors.initials: J
authors.lastname: Quarleri
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications* / Q000821:virology*; D058507:Host Specificity; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D014759:Viral Envelope Proteins
keywords: Genotype 1a; HAART; HCV; HIV coinfection; HVR-1; Quasispecies heterogeneity