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目的探讨具有广谱中和活性的艾滋病病毒-1型(HIV-1)B′亚型毒株感染者,连续五个时间点样本的膜蛋白基因(env)序列的特征。方法采用单基因组扩增法扩增env基因。分析不同时间点env基因序列的特征及代表性广谱中和抗体(bNAbs)表位的变异。结果 env基因系统进化分析发现,感染者体内包含优势和劣势两个不同株系的病毒,优势株系毒株可变区多样性随时间增大,尤以V1V2环序列长度和糖基化位点变异程度最高;优势和劣势株系病毒的顶端四肽分别为GQGR和GPGK,辅助受体均为CCR5。代表性广谱中和抗体表位分析显示,2G12和PG9/PG16识别的关键位点存在变异。结论 B′亚型毒株感染者体内包含优势和劣势两个不同株系的病毒,优势株系病毒在中和选择压力下不断进化;单抗表位变异分析表明,感染者体内可能存在2G12和PG9/PG16样抗体。
Objective To investigate the characteristics of the env sequences of five consecutive samples of HIV-1 B ’subtype infected with broad-spectrum neutralizing activity. Methods The env gene was amplified by single genomic amplification. The characteristics of env gene sequences and the variation of representative broad-spectrum neutralizing antibody (bNAbs) epitopes at different time points were analyzed. Results The phylogenetic analysis of env gene revealed that the diversity of the variable region of dominant strains increased with time, especially the length of V1V2 loop and the number of glycosylation sites The highest degree of variation; dominant and inferior strains of virus top peptide were GQGR and GPGK, co-receptor are CCR5. Representative broad-spectrum neutralizing antibody epitope analysis shows that there are variations in the key sites identified by 2G12 and PG9 / PG16. CONCLUSION: The virus of the two subtypes, dominant and inferior, contained in the infected B ’subtype virus in vivo, and the predominant virus evolved under neutralization selection pressure. The analysis of monoclonal antibody epitope showed that there might be 2G12 and PG9 / PG16-like antibody.