Quasispecies structure, cornerstone of hepatitis B virus infection: Mass sequencing approach

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.