Review
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World J Gastroenterol. Nov 7, 2013; 19(41): 6995-7023
Published online Nov 7, 2013. doi: 10.3748/wjg.v19.i41.6995
Quasispecies structure, cornerstone of hepatitis B virus infection: Mass sequencing approach
Francisco Rodriguez-Frias, Maria Buti, David Tabernero, Maria Homs
Francisco Rodriguez-Frias, Maria Buti, David Tabernero, Maria Homs, Network Medical Research Center, Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, 08036 Barcelona, Spain
Francisco Rodriguez-Frias, David Tabernero, Maria Homs, Department of Biochemistry, Vall d’Hebron Hospital, Autonomous University of Barcelona, 08035 Barcelona, Spain
Maria Buti, Department of Hepatology, Vall d’Hebron Hospital, Autonomous University of Barcelona, 08035 Barcelona, Spain
Author contributions: All the authors contributed to writing the manuscript.
Supported by Instituto de Salud Carlos III, grant PI12/1893, co-financed by the European Regional Development Fund (ERDF) and Instituto Carlos III of the Spanish Ministry of Health and Consumer Affairs
Correspondence to: Francisco Rodriguez-Frias, PhD, Proteins, Hepatitis and Molecular Genetics Unit, Department of Biochemistry, Vall d’Hebron Hospital, Autonomous University of Barcelona, Paseo Vall d’Hebron 19-129, 08035 Barcelona, Spain. frarodri@vhebron.net
Telephone: +34-93-274-6991 Fax: +34-93-274-6831
Received: June 28, 2013
Revised: August 23, 2013
Accepted: September 15, 2013
Published online: November 7, 2013
Processing time: 141 Days and 2.9 Hours
Abstract

Hepatitis B virus (HBV) is a DNA virus with complex replication, and high replication and mutation rates, leading to a heterogeneous viral population. The population is comprised of genomes that are closely related, but not identical; hence, HBV is considered a viral quasispecies. Quasispecies variability may be somewhat limited by the high degree of overlapping between the HBV coding regions, which is especially important in the P and S gene overlapping regions, but is less significant in the X and preCore/Core genes. Despite this restriction, several clinically and pathologically relevant variants have been characterized along the viral genome. Next-generation sequencing (NGS) approaches enable high-throughput analysis of thousands of clonally amplified regions and are powerful tools for characterizing genetic diversity in viral strains. In the present review, we update the information regarding HBV variability and present a summary of the various NGS approaches available for research in this virus. In addition, we provide an analysis of the clinical implications of HBV variants and their study by NGS.

Keywords: Hepatitis B virus; Next generation sequencing; Quasispecies; Linkage analysis; Gene overlapping

Core tip: We provide an update of hepatitis B virus (HBV) virology, focusing on its complex replication cycle which generates high genetic variability, which led HBV infection to evolve as viral quasispecies, complex distributions of variant populations that are closely related but not identical. We also discuss the clinical and virological implications of this population structure and the application of different next-generation sequencing approaches, which enable analysis of thousands of clonally amplified regions, to study these heterogeneous viral populations.