HIV-1 B′亚型毒株感染者广谱中和活性样本不同时间点env基因变异研究

Study on env gene variation of an HIV-1 clade B′ infected subject with broadly neutralizing activities at different time points

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 analyze the characteristics of envsequences in an HIV-1clade B＇infected subject with broadly neutralizing activities at 5different time points.Methods HIV-1envelope gene was amplified by single genome amplification（SGA）.The evolution,diversity of env sequences,and the mutations of antigenic epitopes of representative broadly neutralizing antibodies（bNabs）were analyzed.Results Phylogenetic analysis of env sequences found two separate lineages of viruses：the dominant cluster and the inferior cluster,in the study subject.The variable loop diversity of the dominant viruses had a tendency to increase over time,especially for V1V2 sequence length and PNGS number.Both of the two clusters of viruses used CCR5 as co-receptor,and had different crown tetra-peptides,with the dominant cluster being GQGR and the inferior cluster being GPGK,respectively.Analysis of antigenic epitopes of representative bNabs demonstrated key amino acid mutation of 2G12,PG9/PG16 antibodies.Conclusion There are two separate lineages of viruses in the study subject,and the dominant virus strains evolve continuously under the neutralizing selective pressures.Epitope analysis of variance shows that 2G12 and PG9/PG16class-like antibodies may be present.