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广谱中和活性样本HIV-1 Env基因的氨基酸及密码子使用特点研究

Characteristics of amino acid and codon usage of Env genes in HIV-1 infected individuals with highly broad cross-neutralizing activity

摘要目的:分析具有高广谱中和活性的HIV-1感染者包膜蛋白( Env)基因的氨基酸及密码子使用特点。 方法:根据中和宽度是否高于90%将样本分为高广谱中和活性组(hBCN +组)和非高广谱中和活性组(hBCN -组),采用单拷贝基因组扩增法(SGA)分离全长 Env基因,通过两组样本 Env基因的相对氨基酸使用度(RAAU)的对应性分析(COA),并基于相似性指数 D( A, B)计算及与宿主相对密码子使用度(RSCU)的比对探讨两组毒株的氨基酸及密码子使用特点。 结果:对应性分析结果显示hBCN +组和hBCN -组毒株RAAU数据沿两个主轴分布形成两个相对独立的簇,表明两组毒株 Env基因具有相对独特的氨基酸使用模式;相似性指数分析结果显示hBCN +组(0.097)低于hBCN -组(0.102),且两组毒株相比较,hBCN +组 Env基因与人具有相似使用模式的密码子少于hBCN -组,提示hBCN +组毒株在感染者体内的适应性较hBCN -组毒株低。 结论:hBCN +和hBCN -两组毒株的 Env基因具有相对独特的氨基酸使用模式,hBCN +组毒株对宿主的适应性较hBCN -组毒株低。

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abstractsObjective:To study the amino acid and codon usage profile of HIV-1 Env gene in donors whose serum exhibit highly broad cross-neutralizing activity. Methods:The samples were divided into highly broad cross-neutralizing activity group (hBCN + group) and non-highly broad cross-neutralizing activity group (hBCN - group) based on whether the neutralization breadth was higher than 90% or not. Full-length Env genes were amplified by single genome amplification (SGA) method from patients′ plasma samples, and the characteristics of Env sequences in hBCN + group were compared with hBCN - group. The correspondence analysis (COA) on relative amino acid usage (RAAU), adaptability to host based on similarity index D( A, B) and relative synonymous codon usage (RSCU) values of Env genes (hBCN + and hBCN -) with respect to human host RSCU were analyzed. Results:Correspondence analysis showed that the RAAU data of hBCN + group and hBCN - group were distributed along the two main axes to form two relatively separated clusters, indicating that the Env genes of the two groups had relatively unique amino acid usage patterns; the similarity index calculation results showed that hBCN + group (0.097) was lower than the hBCN - group (0.102), in addition, the Env gene of the hBCN + group had less frequency of similarly selected codons with human host system compared to hBCN - group. Conclusions:Env genes in hBCN + group and hBCN - group may have relatively unique amino acid usage patterns, and virus strains in hBCN + group are less adaptable to the host than those in hBCN - group.

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