Department of Microbiology, Peking University Health Science Center, Xueyuan Road 38, Haidian District, 100191 Beijing, China.
Antiviral Res. 2010 Mar;85(3):512-9. doi: 10.1016/j.antiviral.2009.12.006. Epub 2009 Dec 23.
Full-length hepatitis B virus (HBV) reverse transcriptase (RT) sequences were amplified and sequenced among 192 nucleos(t)ide analogue (NA)-naïve Chinese patients with chronic hepatitis B. Deduced amino acids (AAs) at 42 previously reported potential NA resistance (NAr) mutation positions in RT region were analyzed. Patients were found with either B-genotype (28.65%) or C-genotype (71.35%) infections. Rt53, rt91, rt124, rt134, rt221, rt224, rt238 and rt256 were identified as B- and C-genotype-dependent polymorphic AA positions. AA substitutions at 11 classical NAr mutation positions, i.e. rt80, rt169, rt173, rt180, rt181, rt184, rt194, rt202, rt204, rt236 and rt250, were not detected. However, potential NAr mutations were found in 30.73% (59/192) isolates, which involved 18 positions including rt53, rt207, rt229, rt238 and rt256, etc. The concomitant AA changes of HBsAg occurred in 16.67% (32/192) isolates including sG145R mutation. One-third of mutation positions were located in functional RT domains (e.g. rt207 and rt233), A-B interdomains (overlapping HBsAg 'a' determinant and showing most concomitant immune-associated mutations) and non-A-B interdomains (e.g. rt191 and rt213), respectively. Genotypes B and C each showed several preferred positions to mutate. These results might provide insights into understanding the evolution and selection basis of NAr HBV strains under antiviral therapy.
对 192 例初治慢性乙型肝炎核苷（酸）类似物（NA）患者的全长乙型肝炎病毒（HBV）逆转录酶（RT）序列进行了扩增和测序。对 RT 区 42 个先前报道的潜在 NA 耐药（NAr）突变位置的推断氨基酸（AA）进行了分析。患者的感染基因型为 B 型（28.65%）或 C 型（71.35%）。Rt53、rt91、rt124、rt134、rt221、rt224、rt238 和 rt256 被确定为 B 型和 C 型依赖性多态性 AA 位置。在 11 个经典 NAr 突变位置（rt80、rt169、rt173、rt180、rt181、rt184、rt194、rt202、rt204、rt236 和 rt250）未检测到 AA 取代。然而，在 30.73%（59/192）的分离物中发现了潜在的 NAr 突变，涉及 18 个位置，包括 rt53、rt207、rt229、rt238 和 rt256 等。在 192 个分离物中，有 16.67%（32/192）发生了 HBsAg 伴随的 AA 变化，包括 sG145R 突变。三分之一的突变位置位于功能 RT 结构域（如 rt207 和 rt233）、A-B 结构域之间（重叠 HBsAg“a”决定簇并显示出大多数伴随的免疫相关突变）和非 A-B 结构域之间（如 rt191 和 rt213）。基因型 B 和 C 各自显示出几个优先突变的位置。这些结果可能有助于理解抗病毒治疗下 NArHBV 株的进化和选择基础。
