中华皮肤科杂志 ›› 2012, Vol. 45 ›› Issue (10): 731-734.

• 论著 • 上一篇    下一篇

HIV-1 V2区突变对CD4结合位点中和抗体识别的影响

刘沐桑1,松下修三2,柴田润二2,刘维达3   

  1. 1. 中国医学科学院北京协和医学院皮肤病研究所
    2. 日本熊本大学
    3. 南京 中国医学科学院北京协和医学院皮肤病研究所
  • 收稿日期:2011-11-09 修回日期:2011-12-23 出版日期:2012-10-15 发布日期:2012-09-29
  • 通讯作者: 刘维达 E-mail:liumyco@hotmail.com

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

  • Received:2011-11-09 Revised:2011-12-23 Online:2012-10-15 Published:2012-09-29

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摘要：

目的 探讨HIV-1病毒包膜蛋白gp120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gp120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-FL WT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-FL L175P gp120的结合强度均明显高于它们与野生型JR-FL WT gp120的结合强度。结论 HIV-1 V2区突变可影响中和抗体的抗病毒效果。

关键词: 中和抗体

Abstract:

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 gp120. Methods HIV-1 pseudoviruses （JR-FL） containing wild type or V2-mutant gp120 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-induced NAbs to wild type or V2-mutant gp120. 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 gp120 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 gp120, while the ELISA binding curves of wild type and mutant gp120 against CD4-induced NAbs were separate, and the affinity of CD4-induced NAbs to the mutant gp120 （L175P） was notably higher than that to the wild type gp120. Conclusion The mutations in the V2 domain of HIV-1 gp120 may affect the antiviral activity of NAbs.

Key words: Neutralizing Antibody