Convergence and coevolution of hepatitis B virus drug resistance.
Nat Commun
; 3: 789, 2012 Apr 17.
Article
em En
| MEDLINE
| ID: mdl-22510694
ABSTRACT
Treatment with lamivudine of patients infected with hepatitis B virus (HBV) results in a high rate of drug resistance, which is primarily associated with the rtM204I/V substitution in the HBV reverse transcriptase domain. Here we show that the rtM204I/V substitution, although essential, is insufficient for establishing resistance against lamivudine. The analysis of 639 HBV whole-genome sequences obtained from 11 patients shows that rtM204I/V is independently acquired by more than one intra-host HBV variant, indicating the convergent nature of lamivudine resistance. The differential capacity of HBV variants to develop drug resistance suggests that fitness effects of drug-resistance mutations depend on the genetic structure of the HBV genome. An analysis of Bayesian networks that connect rtM204I/V to many sites of HBV proteins confirms that lamivudine resistance is a complex trait encoded by the entire HBV genome rather than by a single mutation. These findings have implications for public health and offer a more general framework for understanding drug resistance.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus da Hepatite B
/
Evolução Molecular
/
Farmacorresistência Viral
/
Hepatite B
Limite:
Adult
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article