乙型肝炎病毒基因型与聚合酶基因异质性

Hepatitis B virus genotypes and the heterogeneity of its polymerase gene

目的 对202株乙型肝炎病毒(HBV)聚合酶基因(P基因)序列进行系统分析,研究HBV基因型间P基因差异,为进一步研究HBV基因型、P基因变异与病毒复制及核苷类似物耐药的关系提供参考。 方法采用计算机软件对GenBank中已发表的202株HBV全序列及P基因进行分析比较。 结果 HBV P基因在各基因型具有自身特点:在反转录酶(rt)区,A基因型氨基酸的型内差异较小,C、D基因型氨基酸的型内差异较大;在rt区A～F 6个高度保守区域,发现在基因型间及型内存在氨基酸水平的差异。 结论 (1)P基因及其氨基酸存在基因型间和型内异质性,因而分析某些氨基酸差异是与耐药有关还是准株被选择的结果,应综合考虑在该位点是否存在基因型间或型内的氨基酸差异;(2)对核苷类似物抗病毒治疗应答以及治疗中耐药现象的发生在HBV不同基因型可能不同。

Objective To study the heterogeneity of polymerase gene (P gene) within hepatitis B virus (HBV) genotypes based on a systematic analysis of 202 HBV P genes, providing some useful references for further studies on the relationship among HBV genotypes, P gene mutations, replication and nucleoside analogues drug-resistance. Methods 202 HBV complete sequences containing P genes were obtained from GenBank and were analysed using computer softwares. Results There were some genotype-related characteristics of HBV P genes. As reverse transcriptase domain was concerned, there were more amino acid divergences in genotype C and D compared with these in genotype A. There were also amino acid substitutions in the A-F conserved regions of the reverse transcriptase domain within and between HBV genotypes. Conclusions There are divergences of P genes and amino acids within and between HBV genotypes, which should be considered when amino acid changes are analyzed whether they are proposed to be drug-resistance mutations or the results from quasispecies-selected. Moreover, these divergences may affect the antiviral effect of nucleoside analogues on HBV with different genotypes.