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

作　　者：孙莎莎 胡园园[1] 刘颖[1] 任莉[1] 阮玉华[1] 马丽英[1] 邵一鸣 洪坤学[1] Sun Shasha;Hu Yuanyuan;Liu Ying;Ren Li;Ruan Yuhua;Ma Liying;Shao Yiming;Hong Kunxue(National Center for AIDS/STD Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China)

机构地区：[1]中国疾病预防控制中心性病艾滋病预防控制中心,传染病预防控制国家重点实验室,北京102206

出　　处：《中华微生物学和免疫学杂志》2021年第5期338-344,共7页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金(81172809);国家传染病预防控制重大专项(2018ZX10731-101);传染病预防控制国家重点实验室重点项目(2019SKLID602)。

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。Objective 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.

关 键 词：HIV-1 膜蛋白 高广谱中和活性 相对氨基酸使用度(RAAU) 相对密码子使用度(RSCU) 

分 类 号：R512.91[医药卫生—内科学]