Distinct quasispecies characteristics and positive selection within precore/core gene in hepatitis B virus HBV associated acute‐on‐chronic liver failure

Abstract

The ACLF patients showed distinct quasispecies characteristics with higher complexity and diversity within the HBV precore/core gene. The increased HBV quasispecies complexity and diversity, together with a distinct set of positive selection sites, is likely associated with the development of ACLF.

Coexistence of Hepatitis B Virus Quasispecies Enhances Viral Replication and the Ability To Induce Host Antibody and Cellular Immune Responses

“…It was suspected that these mutations may contribute to the development of LF (1,(6)(7)(8). However, most of these results were based on in vitro transfection of single HBV replication-competent plasmids with such mutations.…”

“…It has been previously reported that coinfection with human immunodeficiency virus (HIV) and HBV results in low quasispecies complexity (4). In patients with HBV infection-related liver failure (HB-LF), the quasispecies showed distinct characteristics with higher complexity and diversity within the HBV precore (preC)/core gene (6). However, there is no clear experimental evidence for a significant role of HBV quasispecies in the pathogenesis of HB-LF.…”

“…HBV mutants are thought to play a role in the progression of HBV-associated liver diseases (1,(6)(7)(8). The HBV population in the host exists in the form of quasispecies and contains a wide spectrum of mutants (5).…”

“…Some mutations in HBV genomes, such as the A1762T/G1764A double mutation in the basal core promoter (BCP) and the G1896A mutation in the preC region, are thought to play a role in the progression of liver diseases (1,(6)(7)(8). These mutations were found to enhance HBV replication in vitro and to abrogate expression of hepatitis B virus e antigen (HBeAg), which is suspected to interrupt immune tolerance in the host and to contribute to the development of LF (1,7,8).…”

Variations and mutations in the hepatitis B virus genome and their associations with clinical characteristics

“…By contrast, line probe assays can detect specific variants occurring in > 5% of viral quasispecies [38,39] . Other highly sensitive methods include restriction fragment length polymorphism analysis [40] , clone-based sequencing [41] , and real-time PCR. More recently, several next-generation sequencing methods have been developed, including ultra-deep pyrosequencing, which can detect thousands of clonally amplified regions [42][43][44][45] .…”