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Convergence and coevolution of Hepatitis B virus drug resistance

Author

Listed:
  • Hong Thai

    (Molecular Epidemiology and Bioinformatics Laboratory, Center for Disease Control and Prevention)

  • David S. Campo

    (Molecular Epidemiology and Bioinformatics Laboratory, Center for Disease Control and Prevention)

  • James Lara

    (Molecular Epidemiology and Bioinformatics Laboratory, Center for Disease Control and Prevention)

  • Zoya Dimitrova

    (Molecular Epidemiology and Bioinformatics Laboratory, Center for Disease Control and Prevention)

  • Sumathi Ramachandran

    (Molecular Epidemiology and Bioinformatics Laboratory, Center for Disease Control and Prevention)

  • Guoliang Xia

    (Molecular Epidemiology and Bioinformatics Laboratory, Center for Disease Control and Prevention)

  • Lilia Ganova-Raeva

    (Molecular Epidemiology and Bioinformatics Laboratory, Center for Disease Control and Prevention)

  • Chong-Gee Teo

    (Molecular Epidemiology and Bioinformatics Laboratory, Center for Disease Control and Prevention)

  • Anna Lok

    (University of Michigan Health System)

  • Yury Khudyakov

    (Molecular Epidemiology and Bioinformatics Laboratory, Center for Disease Control and Prevention)

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.

Suggested Citation

  • Hong Thai & David S. Campo & James Lara & Zoya Dimitrova & Sumathi Ramachandran & Guoliang Xia & Lilia Ganova-Raeva & Chong-Gee Teo & Anna Lok & Yury Khudyakov, 2012. "Convergence and coevolution of Hepatitis B virus drug resistance," Nature Communications, Nature, vol. 3(1), pages 1-8, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1794
    DOI: 10.1038/ncomms1794
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