Convergence and coevolution of Hepatitis B virus drug resistance

  • Thai H
  • Campo D
  • Lara J
 et al. 
  • 32

    Readers

    Mendeley users who have this article in their library.
  • 26

    Citations

    Citations of this article.

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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Hong Thai

  • David S. Campo

  • James Lara

  • Zoya Dimitrova

  • Sumathi Ramachandran

  • Guoliang Xia

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free