HIV-1 V2区突变对CD4结合位点中和抗体识别的影响  

Impact of mutations in the V2 domain of HIV-1 envelop glycoprotein 120 on the recognition of neutral- izing antibodies targeting the CD4-binding site

作　　者：刘沐桑[1] 松下修三 柴田润二[2] 刘维达[1] 

机构地区：[1]中国医学科学院北京协和医学院皮肤病研究所,南京210042 [2]日本熊本大学艾滋病中心

出　　处：《中华皮肤科杂志》2012年第10期731-734,共4页Chinese Journal of Dermatology

摘　　要：目的探讨HIV-1病毒包膜蛋白gpl20的V2区突变对其他结构域的中和抗体识别的影响。方法使用假病毒构建系统包装野生型和V2区突变型的HIV-1假病毒，分别测试抗CD4结合位点中和抗体和CD4诱导的中和抗体对两种病毒的中和作用。使用双抗体夹心ELISA法测试CD4结合位点中和抗体和CD4诱导的中和抗体对gpl20野生型和突变型蛋白的亲合力。结果CD4结合位点中和抗体和CD4诱导的中和抗体均无法中和野生株JR—FLWT假病毒，但2种中和抗体对V2突变株的中和活性显著提高，在低浓度下即可中和该病毒。野生株和突变株gp120单体与抗CD4结合位点中和抗体的结合力无明显差异，而gp120单体与CD4诱导的中和抗体的结合实验ELISA曲线却明显分离，CD4诱导的中和抗体与突变型JR—FLL175Pgp120的结合强度均明显高于它们与野生型JR-FLwTgp120的结合强度。结论HIV-1V2区突变可影响中和抗体的抗病毒效果。Objective To investigate the impact of mutations in the V2 domain of HIV-1 envelop glycoprotein （gp） 120 gene on the recognition of neutralizing antibodies （NAbs） specific to the other domains of gpl20. Methods HIV-1 pseudoviruses （JR-FL） containing wild type or V2-mutant gpl20 monomers were constructed, and the neutralization of CD4-binding site-specific and CD4-induced NAbs to the HIV-1 pseudoviruses was observed. Enzyme linked immunosorbent assay （ELISA） was performed to evaluate the binding affinity of CD4-binding site-specific and CD4-indueed NAbs to wild type or V2-mntant gpl20. Results Neither CD4-binding site-specific nor CD4-induced NAbs could neutralize the wild type JR-FL pseudoviruses, but both of them could neutralize pseudoviruses containg the gpl20 V2 mutant at a low concentration. There was no significant difference in the binding affinity to CD4-binding site-specific NAbs between the wild type and mutant gpl20, while the ELISA binding curves of wild type and mutant gpl20 against CD4-indnced NAbs were separate, and the affinity of CD4-indueed NAbs to the mutant gpl20 （L175P） was notably higher than that to the wild type gp120. Conclusion The mutations in the V2 domain of HIV-1 gpl20 may affect the antiviral activity of NAbs.

关 键 词：HIV-1 突变 中和抗体 

分 类 号：R392[医药卫生—免疫学]