抗体介导的尖峰激活促进了SARS-CoV-2的细胞间传播
Shi Yu1, Xu Zheng1, Yanqiu Zhou2
1The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology & Immunology, Shanghai Institute of Immunity and Infection, University of Chinese Academy of Sciences, Shanghai, China.
PLoS pathogens
|November 10, 2023
概括
针对SARS-CoV-2尖端蛋白的抗体可以触发细胞融合,绕过中和. 抑制这种尖端处理使细胞对抗体重新敏感,为抗击COVID-19变种提供了新的治疗策略.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 新出现的SARS-CoV-2变种对现有的COVID-19治疗方法构成挑战.
- 尖尖糖蛋白通过突形成调解病毒的进入和细胞间传输.
- 尖端介导的细胞-细胞传播显示出通过未知的机制对抗体中和的抗性.
研究的目的:
- 为了研究抗体介导的尖峰激活和突触形成的机制.
- 了解SARS-CoV-2如何在细胞间传播中实现抗体抵抗.
- 为了确定改进基于抗体的COVID-19疗法的潜在目标.
主要方法:
- 研究了在表达病毒尖峰的细胞上通过抗体介导的尖峰激活和突触形成.
- 研究了受体结合动机 (RBM) 抗体在尖端处理中的作用.
- 利用S1/S2蛋白解的抑制来评估抗体中和的有效性.
- 评估了细胞外抗体在真实SARS-CoV-2感染期间对细胞病变效应的影响.
主要成果:
- 可溶性RBM抗体诱导了S1/S2和S2'位点的尖端蛋白质分解过程,触发了ACE2独立的细胞融合.
- 抗体诱导的融合需要S1脱落和融合暴露.
- 抑制S1/S2蛋白质溶解恢复了spike介导细胞融合的抗体中和 in vitro.
- 细胞外中和抗体没有影响来自真实SARS-CoV-2感染的细胞病变效应.
结论:
- SARS-CoV-2采用一种新的抗体逃避机制,涉及抗体诱导的尖端激活和细胞-细胞融合.
- 了解这种机制为选择和设计针对SARS-CoV-2的抗体提供了洞察力.
- 向尖端蛋白质分解可以提高抗体治疗对感染细胞的疗效.
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