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    Composition and Interactions of Hepatitis B Virus Quasispecies Defined the Virological Response During Telbivudine Therapy

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    Author
    Zhou, B; Dong, H; He, Y; Sun, J; Jin, W; Xie, Q; Fan, R; Wang, M; Li, R; Chen, Y; ...
    Date
    2015-11-24
    Source Title
    Scientific Reports
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Locarnini, Stephen
    Affiliation
    Microbiology and Immunology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Zhou, B., Dong, H., He, Y., Sun, J., Jin, W., Xie, Q., Fan, R., Wang, M., Li, R., Chen, Y., Xie, S., Shen, Y., Huang, X., Wang, S., Lu, F., Jia, J., Zhuang, H., Locarnini, S., Zhao, G. -P. ,... Hou, J. (2015). Composition and Interactions of Hepatitis B Virus Quasispecies Defined the Virological Response During Telbivudine Therapy. SCIENTIFIC REPORTS, 5 (1), https://doi.org/10.1038/srep17123.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/259063
    DOI
    10.1038/srep17123
    Abstract
    Reverse transcriptase (RT) mutations contribute to hepatitis B virus resistance during antiviral therapy with nucleos(t)ide analogs. However, the composition of the RT quasispecies and their interactions during antiviral treatment have not yet been thoroughly defined. In this report, 10 patients from each of 3 different virological response groups, i.e., complete virological response, partial virological response and virological breakthrough, were selected from a multicenter trial of Telbivudine treatment. Variations in the drug resistance-related critical RT regions in 107 serial serum samples from the 30 patients were examined by ultra-deep sequencing. A total of 496,577 sequence reads were obtained, with an average sequencing coverage of 4,641X per sample. The phylogenies of the quasispecies revealed the independent origins of two critical quasispecies, i.e., the rtA181T and rtM204I mutants. Data analyses and theoretical modeling showed a cooperative-competitive interplay among the quasispecies. In particular, rtM204I mutants compete against other quasispecies, which eventually leads to virological breakthrough. However, in the absence of rtM204I mutants, synergistic growth of the drug-resistant rtA181T mutants with the wild-type quasispecies could drive the composition of the viral population into a state of partial virological response. Furthermore, we demonstrated that the frequency of drug-resistant mutations in the early phase of treatment is important for predicting the virological response to antiviral therapy.

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