TY - JOUR
T1 - Clinical application of estimating hepatitis b virus quasispecies complexity by massive sequencing: Correlation between natural evolution and on-treatment evolution
AU - Homs, Maria
AU - Caballero, Andrea
AU - Gregori, Josep
AU - Tabernero, David
AU - Quer, Josep
AU - Nieto, Leonardo
AU - Esteban, Rafael
AU - Buti, Maria
AU - Rodriguez-Frias, Francisco
PY - 2014/11/13
Y1 - 2014/11/13
N2 - © 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.
AB - © 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.
U2 - https://doi.org/10.1371/journal.pone.0112306
DO - https://doi.org/10.1371/journal.pone.0112306
M3 - Article
VL - 9
IS - 11
M1 - e112306
ER -
