膜HIV-1包膜糖蛋白在预先触发的构造中比自然病毒Envs更强烈地稳定
Zhiqing Zhang1,2, Saumya Anang1,2, Hanh T Nguyen1,2
1Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
iScience
|July 9, 2024
概括
稳定人类免疫缺陷病毒 (HIV-1) 包膜糖蛋白 (Env) 的预触发形状揭示了它在病毒进入和抗体中和中的作用. 这项工作有助于理解HIV-1 Env结构-功能关系.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 人类免疫缺陷病毒 (HIV-1) 包膜糖蛋白 (Env) 缩剂的预触发形状是抗病毒药物和广泛中和抗体 (bNAbs) 的关键目标.
- 这种预先触发的Env形状的固有不稳定性限制了详细的结构和功能表征.
研究的目的:
- 在预先触发的构造中生成和表征稳定膜结合的HIV-1 Env变体.
- 调查预触发Env稳定性对其协会的影响,对bNAbs的敏感性,以及病毒进入和细胞融合中的作用.
主要方法:
- 生产膜Env变体,在预触发的构造中稳定性逐渐增加.
- 评估三元子单元的关联,对bNAb中和的敏感性,细胞融合和病毒的进入.
- 在病毒与宿主细胞接触时,评估稳定Env突变体中gp120 V3区域的可访问性.
主要成果:
- 增加预触发的Env稳定性与较强的三元体子单元关联相关.
- 稳定Env变种对bNAb中和的敏感性增加.
- 增强的Env稳定性导致细胞融合和病毒进入的能力下降.
- 高度稳定的Env突变使gp120 V3区域暴露在细胞参与后的抗体中.
结论:
- 对HIV-1 Env的进化压力平衡了三元体的完整性,CD4受体的响应性和抗体的抗性.
- 稳定预触发膜Env变体提供了宝贵的工具,进一步表征这一关键的形状.
- 了解预触发的Env稳定性对于开发有效的HIV-1进入抑制剂和bNAbs至关重要.
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