A replicon-based shuttle vector system for assessing the phenotype of HCV NS5B polymerase genes isolated from patient populations.
J Virol Methods
; 145(2): 137-45, 2007 Nov.
Article
em En
| MEDLINE
| ID: mdl-17604129
ABSTRACT
Hepatitis C virus (HCV) replicon-based shuttle vectors that permit phenotypes of NS5B polymerase genes from a large number of patient isolates to be rapidly assessed when transiently expressed in cultured cells were designed. When used to test responses to an inhibitor of HCV RNA-dependent RNA polymerase, IC(50) values for inhibition covered a several hundred-fold range among 47 patient samples tested. This observation highlights the variability that can be found by testing isolates derived from HCV-infected subjects. Partial suppression with a polymerase inhibitor of the most sensitive species permitted detection of minor quasispecies that were 7-200-fold more resistant than the bulk population in approximately half of the samples. Sequence analysis showed a wide range of amino acid changes not detected by conventional selection methods using laboratory-derived strains. This approach provides a means to assess variation in antiviral efficacy, and to predict possible responses in a clinical setting.
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Base de dados:
MEDLINE
Assunto principal:
Replicon
/
RNA Polimerase Dependente de RNA
/
Hepatite C
/
Proteínas não Estruturais Virais
/
Hepacivirus
/
Vetores Genéticos
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article