Complex Genotype Mixtures Analyzed by Deep Sequencing in Two Different Regions of Hepatitis B Virus
Caballero, Andrea (Hospital Universitari Vall d'Hebron)
Gregori i Font, Josep (Roche Diagnostics S.L., Sant Cugat del Vallès)
Homs, Maria (Hospital Universitari Vall d'Hebron)
Tabernero, David (Hospital Universitari Vall d'Hebron)
González, Carolina (Hospital Universitari Vall d'Hebron)
Quer, Josep 1963- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Blasi, Maria (Hospital Universitari Vall d'Hebron)
Casillas, Rosario (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Nieto, Leonardo (Hospital Universitari Vall d'Hebron)
Riveiro Barciela, Mar (Hospital Universitari Vall d'Hebron)
Esteban, Rafael (Esteban Mur) (Hospital Universitari Vall d'Hebron)
Buti, Maria (Hospital Universitari Vall d'Hebron)
Rodríguez Frías, Francisco (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2015
Abstract:	This study assesses the presence and outcome of genotype mixtures in the polymerase/surface and X/preCore regions of the HBV genome in patients with chronic hepatitis B virus (HBV) infection. Thirty samples from ten chronic hepatitis B patients were included. The polymerase/surface and X/preCore regions were analyzed by deep sequencing (UDPS) in the first available sample at diagnosis, a pre-treatment sample, and a sample while under treatment. HBV genotype was determined by phylogenesis. Quasispecies complexity was evaluated by mutation frequency and nucleotide diversity. The polymerase/surface and X/preCore regions were validated for genotyping from 113 GenBank reference sequences. UDPS yielded a median of 10,960 sequences per sample (IQR 16,645) in the polymerase/surface region and 11595 sequences per sample (IQR 14,682) in X/preCore. Genotype mixtures were more common in X/preCore (90%) than in polymerase/surface (30%) (p<0. 001). On X/preCore genotyping, all samples were genotype A, whereas polymerase/surface yielded genotypes A (80%), D (16. 7%), and F (3. 3%) (p = 0. 036). Genotype changes in polymerase/surface were observed in four patients during natural quasispecies dynamics and in two patients during treatment. There were no genotype changes in X/preCore. Quasispecies complexity was higher in X/preCore than in polymerase/surface (p = 0. 004). The results provide evidence of genotype mixtures and differential genotype proportions in the polymerase/surface and X/preCore regions. The genotype dynamics in HBV infection and the different patterns of quasispecies complexity in the HBV genome suggest a new paradigm for HBV genotype classification.
Grants:	Ministerio de Economía y Competitividad PI12/01893
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 10 (december 2015) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0144816
PMID: 26714168

15 p, 563.3 KB

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