Clinical Application of Estimating Hepatitis B Virus Quasispecies Complexity by Massive Sequencing : Correlation between Natural Evolution and On-Treatment Evolution
Homs, Maria (Hospital Universitari Vall d'Hebron)
Caballero, Andrea (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gregori i Font, Josep (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Tabernero, David (Hospital Universitari Vall d'Hebron)
Quer, Josep 1963- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Nieto, Leonardo (Hospital Universitari Vall d'Hebron)
Esteban, Rafael (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Buti, Maria (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rodríguez Frías, Francisco (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Data:	2014
Resum:	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. 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. 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+. 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.
Ajuts:	Ministerio de Economía y Competitividad PI12/01893
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 9 (november 2014) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0112306
PMID: 25393280

13 p, 974.8 KB

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