Molecular evolution of hepatitis B virus over 25 years
Molecular evolution of hepatitis B virus over 25 years
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DOI：
10.1128/jvi.00996-06
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发表时间：
2006-11-01
影响因子：
5.4
通讯作者：
Minuk, Gerald Y.
中科院分区：
文献类型：
--
作者：
Osiowy, Carla;Giles, Elizabeth;Minuk, Gerald Y.
由于乙肝病毒基因组的复杂性，以及需要研究长时间收集的配对样本，确定乙肝病毒(HBV)的纵向分子进化是困难的。在这项研究中，收集了1979和2004年间8名HBVe抗原阴性的无症状HBVB型携带者的系列样本，从而提供了25年的时间来记录HBVe抗原的长期分子进化。通过对全长的乙肝病毒基因组序列进行系统进化和线性回归分析，确定了25年来出现的突变的比率、性质和分布。在聚合酶和前S/S重叠区以及核心基因内观察到核苷酸高度变异性。计算出的每部位/年的平均核苷酸取代数(7.9×10(-5))略高于已发表的估计(1.5×10(-5)至5×10(-5))。基于序列克隆前S区域序列进化距离的线性回归分析，准种群体中的核苷酸变化没有显著改变分子进化速度。因此，直接扩增的或显性的序列足以估计这些长期序列样本的假定分子进化速度。平均而言，聚合酶编码区同义替换(d(S))与非同义替换(d(N))的比率最高，核心编码区最低。在核心区域观察到的较低的d(S)/d(N)比率表明，选择发生在该基因区域内，可能是一种免疫逃避策略。这项研究的结果表明，以宿主免疫阶段依赖的方式，乙肝病毒序列分歧可能发生得比先前估计的更快。
Determining the longitudinal molecular evolution of hepatitis B virus (HBV) is difficult due to HBV's genomic complexity and the need to study paired samples collected over long periods of time. In this study, serial samples were collected from eight hepatitis B virus e antigen-negative asymptomatic carriers of HBV genotype B in 1979 and 2004, thus providing a 25-year period to document the long-term molecular evolution of HBV. The rate, nature, and distribution of mutations that emerged over 25 years were determined by phylogenetic and linear regression analysis of full-length HBV genome sequences. Nucleotide hypervariability was observed within the polymerase and pre-S/S overlap region and within the core gene. The calculated mean number of nucleotide subs titutions/site/year (7.9 X 10(-5)) was slightly higher than published estimates (1.5 X 10(-5) to 5 X 10(-5)). Nucleotide changes in the quasispecies population did not significantly alter the molecular evolutionary rate, based on linear regression analysis of evolutionary distances among serial clone pre-S region sequences. Therefore, the directly amplified or dominant sequence was sufficient to estimate the putative molecular evolutionary rate for these long-term serial samples. On average, the ratio of synonymous (d(S)) to nonsynonymous (d(N)) substitutions was highest for the polymerase-coding region and lowest for the core-coding region. The low d(S)/d(N) ratios observed within the core suggest that selection occurs within this gene region, possibly as an immune evasion strategy. The results of this study suggest that HBV sequence divergence may occur more rapidly than previously estimated, in a host immune phase-dependent manner.