title: Intra-host evolutionary dynamics of hepatitis C virus E2 in treated patients.
abstract: Hepatitis C virus (HCV) displays high genetic diversity. Inter-host sequence variability may mainly reflect a neutral drift evolution. In contrast, intra-host evolution may be driven by an adaptive selection to host responses to infection. Here, HCV E2 intra-host evolution in two patients during the course and follow-up of successive treatments with IFN-alpha and IFN-alpha/ribavirin was investigated. Phylogenetic analyses suggested that adaptive pressures prompt a continuous selection of viral variants derived from the previous ones (intra-lineage evolution) and/or a swapping of viral lineages during the course of the infection (inter-lineage evolution). Selection would act not only on the phenotypic features of hypervariable region 1 (HVR1) but also on those of the flanking regions. The pressures operate mainly at the amino acid level, but they also appeared to act on nucleotide sequences. Moreover, HVR1 heterogeneity seemed to be strongly constrained. This work contributes to the knowledge of HCV intra-host evolution during chronicity.
authors.affiliation: Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 4to piso, Buenos Aires 1113, Argentina.
authors.forename: Victoria
authors.initials: V
authors.lastname: Alfonso
authors.affiliation: Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 4to piso, Buenos Aires 1113, Argentina.
authors.forename: Viviana Andrea
authors.initials: VA
authors.lastname: Mbayed
authors.affiliation: Unidad de Hepatología, Hospital Argerich, Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sookoian
authors.affiliation: Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 4to piso, Buenos Aires 1113, Argentina.
authors.forename: Rodolfo Héctor
authors.initials: RH
authors.lastname: Campos
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004279:DNA, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D019143:Evolution, Molecular; D014644:Genetic Variation; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D008969:Molecular Sequence Data; D010802:Phylogeny; D011994:Recombinant Proteins; D012254:Ribavirin / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D012254:Ribavirin