Temporal variations in the hepatitis C virus intrahost population during chronic infection.
J Virol
; 85(13): 6369-80, 2011 Jul.
Article
em En
| MEDLINE
| ID: mdl-21525348
ABSTRACT
The intrahost evolution of hepatitis C virus (HCV) holds keys to understanding mechanisms responsible for the establishment of chronic infections and to development of a vaccine and therapeutics. In this study, intrahost variants of two variable HCV genomic regions, HVR1 and NS5A, were sequenced from four treatment-naïve chronically infected patients who were followed up from the acute stage of infection for 9 to 18 years. Median-joining network analysis indicated that the majority of the HCV intrahost variants were observed only at certain time points, but some variants were detectable at more than one time point. In all patients, these variants were found organized into communities or subpopulations. We hypothesize that HCV intrahost evolution is defined by two processes incremental changes within communities through random mutation and alternations between coexisting communities. The HCV population was observed to incrementally evolve within a single community during approximately the first 3 years of infection, followed by dispersion into several subpopulations. Two patients demonstrated this pattern of dispersion for the rest of the observation period, while HCV variants in the other two patients converged into another single subpopulation after â¼9 to 12 years of dispersion. The final subpopulation in these two patients was under purifying selection. Intrahost HCV evolution in all four patients was characterized by a consistent increase in negative selection over time, suggesting the increasing HCV adaptation to the host late in infection. The data suggest specific staging of HCV intrahost evolution.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
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Proteínas Virais
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Proteínas não Estruturais Virais
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Hepacivirus
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Evolução Molecular
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Hepatite C Crônica
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Interações Hospedeiro-Patógeno
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article