1These authors contributed equally to this work.
Distinct quasispecies characteristics and positive selection within precore/core gene in hepatitis B virus HBV associated acute-on-chronic liver failure
Article first published online: 22 MAY 2013
© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 28, Issue 6, pages 1040–1046, June 2013
How to Cite
Chen, L., Zheng, C.-X., Lin, M.-h., Huang, Z.-X., Chen, R.-h., Li, Q.-g., Li, Q. and Chen, P. (2013), Distinct quasispecies characteristics and positive selection within precore/core gene in hepatitis B virus HBV associated acute-on-chronic liver failure. Journal of Gastroenterology and Hepatology, 28: 1040–1046. doi: 10.1111/jgh.12109
- Issue published online: 22 MAY 2013
- Article first published online: 22 MAY 2013
- Accepted manuscript online: 27 DEC 2012 05:42AM EST
- Manuscript Accepted: 18 DEC 2012
- National Natural Science Foundation of China. Grant Number: 81000759
- Fuzhou Municipal Science and Technology Projects of China. Grant Number: 2009G102
- National 11th Five-Year Special Grand Project for Infectious Diseases. Grant Number: 20082x10002-005
- hepatitis B virus;
- liver failure;
- molecular evolution;
Background and Aim
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.
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.
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.
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.