title: Distinct quasispecies characteristics and positive selection within precore/core gene in hepatitis B virus HBV associated acute-on-chronic liver failure.
abstract: OBJECTIVE
  The cause of hepatitis B virus associated acute-on-chronic liver failure (ACLF) remains unclear. Quasispecies can contribute to virus persistence and pathogenesis. We used a bioinformatics-based molecular evolution approach to compare quasispecies characteristics and positive selection sites within HBV precore/core gene between ACLF and chronic hepatitis B (CHB) patients.
  
  
  METHODS
  HBV precore/core gene were amplified from 11 ACLF and 10 CHB patients harboring HBV genotype B; following DNA cloning and sequencing quasispecies complexity, diversity, and positive selection sites within the precore/core gene were determined by bioinformatics analysis, and compared between the patient groups.
  
  
  RESULTS
  Both quasispecies complexity (P=0.022 at nucleotide level and 0.008 at amino acid level) and diversity (P<0.05) were found to be significantly greater in ACLF than in CHB. The frequency of G1896/A mutation in ACLF (175/298 clones, 58.7%) was also significantly higher than in CHB (100/230 clones, 43.5%) (P=0.0005). Moreover, analysis of positive selection revealed that significantly more patients with such sites were present in ACLF than in CHB (8/11 VS 2/10, P=0.03); the majority of these positive selection sites lay within HLA-restricted epitopes.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatology, Infectious Disease Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Zheng
authors.forename: Ming-hua
authors.initials: MH
authors.lastname: Lin
authors.forename: Zu-Xiong
authors.initials: ZX
authors.lastname: Huang
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Chen
authors.forename: Qin-guang
authors.initials: QG
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Pan
authors.initials: P
authors.lastname: Chen
mesh_terms: D000328:Adult; D002908:Chronic Disease; D058625:End Stage Liver Disease / Q000150:complications / Q000821:virology; D005260:Female; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D017093:Liver Failure / Q000150:complications / Q000821:virology*; D008297:Male; D014758:Viral Core Proteins / Q000235:genetics*
chemical_list: D014758:Viral Core Proteins