Zhu Yan, Mao Qing, Lan Lin, Hu Ya-jun, Tan Zhao-xia, Zhang Chang-jiang, Wang Yu-ming, Wang Xiao-hong
Institute of Infectious Diseases of Chinese PLA, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2010 Jun;26(6):548-51.
To elucidate adaptive evolution patterns and perform a positive selection analysis of hepatitis C virus(HCV) genotype 1b envelope 2 gene(E2) during natural chronic infection by a longitudinal study.
HCV E2 quasispecies profiles were derived from partially sequenced domains of 6 000 bp recombinant clones. Phylogenetic trees for HCV E2 gene were constructed by MEGA software and the specific codons undergoing diversifying positive selection were identified by FEL method.
HCV phylogenies, coupled with the number and distribution of selected sites were differed markedly between patients. HCV quasispecies complexity during chronic infection was not associated with the evolutionary time and the dominant viriant alternation of HCV quasispecies may occur after more than six months apart. Five sites under positive selection were identified within the ectodomain of the E2 protein.
A series of serum specimens for studies based on dominant viriant of HCV dynamic quasispecies is recommended to be collected at every six months. Several individual sites of HCV E2 gene are under a strong host immune pressure, position aa384, aa399 and aa410 may be involved in escape from neutralizing antibodies, while position aa475, aa522 may correlate to modulate the virus-receptor interaction which result in evading immunity.
通过纵向研究阐明丙型肝炎病毒（HCV）1b基因型包膜2基因（E2）在自然慢性感染期间的适应性进化模式并进行正选择分析。
HCV E2准种谱来自6000 bp重组克隆的部分测序区域。用MEGA软件构建HCV E2基因的系统发育树，并用FEL方法鉴定经历多样化正选择的特定密码子。
患者之间HCV系统发育以及所选位点的数量和分布存在明显差异。慢性感染期间HCV准种的复杂性与进化时间无关，HCV准种的优势变异体交替可能在间隔超过六个月后发生。在E2蛋白的胞外域内鉴定出五个正选择位点。
建议每六个月收集一系列基于HCV动态准种优势变异体的血清标本用于研究。HCV E2基因的几个个别位点受到强烈的宿主免疫压力，第384位、第399位和第410位氨基酸可能参与逃避中和抗体，而第475位、第522位氨基酸可能与调节病毒-受体相互作用有关，从而逃避免疫。
