Amino acid similarities and divergences in the small surface proteins of genotype C hepatitis B viruses between nucleos(t)ide analogue-na茂ve and lamivudine-treated patients with chronic hepatitis B
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- 作者：Hai Ding ; Baoming Liu ; Chengyu Zhao ; Jingxian Yang ; Chunhui Yan ; Ling Yan ; Hui Zhuang ; Tong Li
- 关键词：Hepatitis B virus ; Small hepatitis B surface protein ; Genotype C ; Nucleos(t)ide analogue-naï ; ve ; Lamivudine-treated ; Mutation
- 刊名：Antiviral Research
- 出版年：February, 2014
- 年：2014
- 卷：102
- 期：Complete
- 页码：29-34
- 全文大小：391 K
文摘
Entire C-genotype small hepatitis B surface (SHBs) sequences were isolated from 139 nucleos(t)ide analogues (NA)-na茂ve 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-na茂ve 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 鈥榓鈥?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 鈥榓鈥?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 鈥榓鈥?determinant. Interestingly, another newly-identified truncation mutation sC69stop/rtS78T decreased from 7.91% (11/139) in NA-na茂ve 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.