在病毒与宿主细胞相互作用后,HIV-1颗粒上的广泛中和抗体表位被暴露
Priyanka Gadam Rao1, Gregory S Lambert1, Chitra Upadhyay1
1Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai , New York, New York, USA.
Journal of virology
|September 8, 2023
概括
艾滋病毒-1在其包裹糖蛋白上掩盖了易受伤害的抗体表位,以逃避免疫反应. 这项研究揭示了HIV-1如何隐藏这些部位,以及广泛中和抗体 (bNAbs) 如何克服这种潜在治疗策略的掩盖.
科学领域:
- 免疫学和病毒学
- 病毒的结构生物学
背景情况:
- 人类免疫缺陷病毒1型 (HIV-1) 包裹 (Env) 糖蛋白是中和抗体和疫苗开发的主要目标.
- 在HIV-1 Env上保存的表位通常被掩盖在病毒颗粒上,阻碍有效的幽默免疫反应,并导致病毒免疫逃避.
研究的目的:
- 为了确定哪些Env表位在HIV-1颗粒上暴露或被遮蔽.
- 调查负责掩盖这些关键表征的机制.
- 了解广泛中和抗体 (bNAbs) 如何访问掩盖表位物以进行中和.
主要方法:
- 利用基于流细胞计的测定方法,对三种HIV-1分离物和一组抗体进行了分析.
- 在完整的HIV-1病毒上评估了表皮管可访问性.
- 在抗体前结合和与细胞相互作用后,以及莱克-甘氨酸相互作用后,研究了表皮层暴露.
主要成果:
- 确定V2i,gp120-gp41接口和gp41-MPER表位是可访问的,而V3,V2q和CD4bs表位则被掩盖在HIV-1颗粒上.
- 证明特定抗体的预结合可以诱导全性构造变化,揭开以前无法获得的表位.
- 发现与细胞的相互作用使HIV-1病毒对bNAbs的中和变得敏感,莱克-甘氨酸的相互作用也可以暴露表位.
结论:
- 艾滋病毒-1使用掩蔽策略来封闭bNAbs准的脆弱表位,从而逃避宿主免疫力.
- 抗体结合和病毒与宿主细胞的相互作用可以诱导构造变化,暴露这些掩饰表位,促进中和.
- 研究结果提供了对HIV-1免疫逃避机制的见解,并可以指导设计有效的基于抗体的疗法和疫苗策略.
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