HIV-1广谱中和抗体的结合表位研究

Binding epitopes of HIV-1 broad neutralization antibodies

目的在1例具有广谱中和活性的慢性HIV-1感染者(DRVI01)血浆样本中,分析潜在的中和抗体特异性。方法查找已知的HIV-1广谱中和抗体(bNAbs)的关键氨基酸位点,分析DRVI01来源不同时间点的膜蛋白序列。对存在频繁变异的关键氨基酸位点进行回复突变,比较突变前后的假病毒与自体血浆中和敏感性的差异,推测可能存在的bNAbs。结果在DRVI01来源的6个时间点155条膜蛋白序列中,查找存在频繁突变的10类bNAbs的关键氨基酸位点,其中gp41融合肽、gp120/gp41交界面两类bNAbs的关键氨基酸位点存在较多的变异。对这些位点回复突变后,后一个时间点及同一时间点的自体血浆,对大部分突变株病毒的中和能力明显增强。结论具有广谱中和活性的HIV-1感染者(DRVI01)体内,可能存在与gp41融合肽类及gp120/gp41交界面类bNAbs的中和特异性。

Objective To analyze the potential specificity of broad neutralizing antibodies(bNAbs)in one patient(DRVI01)with chronic HIV-1 infection.Methods Sequences of the envelope glycoprotein(Env)obtained from DRVI01 at different time points were analyzed by comparing with the key amino acids of reported HIV-1 bNAbs in HIV Database.After reverse mutation of key amino acids that had frequently mutated to wild type,the neutralizing sensitivity of autologous plasma against wild-type and mutated Env-pesudoviruses was compared and the potential bNAbs in DRVI01 were speculated.Results Reported key amino acids of 10 bNAbs classes were detected in 155 Env sequences derived from DRVI01.Frequent mutations were found in key amino acids of two bNAbs classes of gp41 fusion domain and gp120/gp41 interface.Neutralizing sensitivity of the contemporaneous autologous plasma and the plasma collected at the next time point against the mutated pesudoviruses was significantly increased as compared with wild-type pesudoviruses.Conclusions Potential NAbs with similar key amino acids to those of gp41 fusion domain and gp120/gp41 interface might present in the HIV-1 infected patient with broad neutralizing antibodies.