Amino acid similarities and divergences in the small surface proteins of genotype C hepatitis B viruses between nucleos(t)ide analogue-naïve and lamivudine-treated patients with chronic hepatitis B.

Abstract

Entire C-genotype small hepatitis B surface (SHBs) sequences were isolated from 139 nucleos(t)ide analogues (NA)-naïve and 74 lamivudine (LMV)-treated chronic hepatitis B (CHB) patients. The conservation and variability of total 226 amino acids (AAs) within the sequences were determined individually, revealing significant higher mutant isolate rate and mutation frequency in LMV-treated cohort than those in the NA-naïve one (P=0.009 and 0.0001, respectively). Three absolutely conserved fragments (s16-s19, s176-s181 and s185-s188) and seven moderately conserved regions (a few AA sites acquiring increased variability after LMV-treatment) were identified. The significant mutation rate increase after LMV-treatment occurred primarily in major hydrophilic region (except 'a' determinant) and transmembrane domain 3/4, but not in other upstream functional regions of SHBs. With little influence on immune escape-associated mutation frequencies within 'a' determinant, LMV-monotherapy significantly induced classical LMVr-associated mirror changes sE164D/rtV173L, sI195M/rtM204V and sW196L/S/rtM204I, as well as non-classical ones sG44E/rtS53N, sT47K/A/rtH55R/Q and sW182stop/rtV191I outside 'a' determinant. Interestingly, another newly-identified truncation mutation sC69stop/rtS78T decreased from 7.91% (11/139) in NA-naïve cohort to 2.70% (2/74) in LMV-treated one. Altogether, the altered AA conservation and diversity in SHBs sequences after LMV-treatment in genotype-C HBV infection might shed new insights into how LMV-therapy affects the SHBs variant evolution and its antigenicity.

• Authors: Hai Ding, Baoming Liu, Chengyu Zhao, Jingxian Yang, Chunhui Yan, Ling Yan, Hui Zhuang, Tong Li
• Journal: Antiviral research (Antiviral Res) Vol. 102 Pg. 29-34 (Feb 2014) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 24316031 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Codon, Nonsense
• Hepatitis B Surface Antigens
• Lamivudine

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Amino Acid Substitution
• Antiviral Agents (therapeutic use)
• Codon, Nonsense
• Female
• Genotype
• Hepatitis B Surface Antigens (genetics)
• Hepatitis B virus (classification, genetics, isolation & purification)
• Hepatitis B, Chronic (drug therapy, virology)
• Humans
• Lamivudine (therapeutic use)
• Male
• Middle Aged
• Mutation, Missense
• Young Adult