Clinical application of estimating hepatitis b virus quasispecies complexity by massive sequencing: Correlation between natural evolution and on-treatment evolution

Maria Homs, Andrea Caballero, Josep Gregori, David Tabernero, Josep Quer, Leonardo Nieto, Rafael Esteban, Maria Buti, Francisco Rodriguez-Frias

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

Abstract

© 2014 Homs et al. Aim: To evaluate HBV quasispecies (QA) complexity in the preCore/Core regions in relation to HBeAg status, and explore QA changes under natural evolution and nucleoside analogue (NUC) treatment. Copyright:Methods: Ultra-deep pyrosequencing of HBV preCore/Core regions in 30 sequential samples (baseline [diagnosis], treatment-free, and treatment-nonresponse) from 10 retrospectively selected patients grouped according to HBeAg status over time: HBeAg+ (N = 4), HBeAg-(N = 2), and fluctuating HBeAg (transient seroreversion/seroconversion pattern) (N = 4). QA complexity was defined by Shannon entropy, mutation frequency, nucleotide diversity, and mutation frequency of amino acids (MfAA) in preCore and Core.Results: The QA was less complex in HBeAg+ than in HBeAg-or fluctuating HBeAg. High complexity in preCore was associated with decreased viral replication (preCore MfAA negatively correlated with HBV-DNA, p = 0.005). QA complexity in the treatment-free period negatively correlated with values seen during treatment. Specific variants were mainly selected in the Core region in HBeAg-and fluctuating HBeAg patients, suggesting higher immune pressure than in HBeAg+.Conclusions: The negative correlation between QA natural evolution and on-treatment evolution indicates the importance of pre-treatment QA study to predict QA changes in NUC nonresponders. Study of QA complexity could be useful for managing HBV infection.
Original languageEnglish
Article numbere112306
JournalPLoS ONE
Volume9
Issue number11
DOIs
Publication statusPublished - 13 Nov 2014

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