Intra-host evolutionary dynamics of hepatitis C virus E2 in treated patients.
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.
Alfonso
Victoria
V
Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 4to piso, Buenos Aires 1113, Argentina.
Mbayed
Viviana Andrea
VA
Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 4to piso, Buenos Aires 1113, Argentina.
Sookoian
Silvia
S
Unidad de Hepatología, Hospital Argerich, Buenos Aires, Argentina.
Campos
Rodolfo Héctor
RH
Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 4to piso, Buenos Aires 1113, Argentina.
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
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