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学科主题: 基础医学
题名:
Amino acid similarities and divergences in the small surface proteins of genotype C hepatitis B viruses between nucleos(t)ide analogue-naive and lamivudine-treated patients with chronic hepatitis B
作者: Ding, Hai1,2; Liu, Baoming1,2,3; Zhao, Chengyu1,2; Yang, Jingxian1,2; Yan, Chunhui1,2; Yan, Ling1,2; Zhuang, Hui1,2; Li, Tong1,2
关键词: Hepatitis B virus ; Small hepatitis B surface protein ; Genotype C ; Nucleos(t)ide analogue-naive ; Lamivudine-treated ; Mutation
刊名: ANTIVIRAL RESEARCH
发表日期: 2014-02-01
DOI: 10.1016/j.antiviral.2013.11.015
卷: 102, 期:0, 页:29-34
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy ; Virology
研究领域[WOS]: Pharmacology & Pharmacy ; Virology
关键词[WOS]: ANTIVIRAL RESISTANCE MUTATIONS ; ESCAPE HBV MUTANTS ; REVERSE-TRANSCRIPTASE ; VACCINE-ESCAPE ; DRUG-RESISTANT ; S-GENE ; POLYMERASE GENE ; THERAPY ; VARIABILITY ; MANAGEMENT
英文摘要:

Entire C-genotype small hepatitis B surface (SHBs) sequences were isolated from 139 nucleos(t)ide analogues (NA)-naive 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-naive 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 nonclassical 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-naive 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. (C) 2013 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 2012ZX10002003-003-013
项目资助者: Major Science and Technology Special Project of China Twelfth Five-year Plan
WOS记录号: WOS:000331485900004
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52127
Appears in Collections:基础医学院_病原生物学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Ctr Infect Dis, Sch Basic Med Sci, Beijing 100191, Peoples R China
3.Univ Tennessee, Ctr Hlth Sci, Dept Microbiol Immunol & Biochem, Memphis, TN 38163 USA

Recommended Citation:
Ding, Hai,Liu, Baoming,Zhao, Chengyu,et al. Amino acid similarities and divergences in the small surface proteins of genotype C hepatitis B viruses between nucleos(t)ide analogue-naive and lamivudine-treated patients with chronic hepatitis B[J]. ANTIVIRAL RESEARCH,2014,102(0):29-34.
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