通过C1q和C4b结合蛋白对SARS-CoV-2感染的补充激活-独立衰减
Nazar Beirag1, Praveen M Varghese1,2, Martin Mayora Neto3
1Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK.
Viruses
|June 28, 2023
概括
补充蛋白C1q和C4b结合蛋白 (C4BP) 通过抑制病毒进入和减少炎症,独立于补充激活,提供对SARS-CoV-2的保护. 这些蛋白质与尖蛋白结合,限制了肺部的感染和炎症反应.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 补体系统对于对病毒的天生的免疫力至关重要.
- 严重的SARS-CoV-2感染包括过度的补体激活和细胞因子风暴.
- 补充蛋白C1q和C4b结合蛋白 (C4BP) 可能对病毒感染有保护作用.
研究的目的:
- 调查C1q和C4BP对抗SARS-CoV-2感染的补充激活独立作用.
- 检查C1q和C4BP与SARS-CoV-2尖端蛋白及其受体结合域 (RBD) 的直接相互作用.
- 评估C1q和C4BP对SARS-CoV-2细胞进入和相关免疫反应的影响.
主要方法:
- 指导ELISA检查蛋白相互作用.
- RT-qPCR用于评估免疫反应调节.
- 使用伪型颗粒进行细胞结合和病毒进入试验.
主要成果:
- C1q和C4BP通过尖端蛋白的RBD直接与SARS-CoV-2伪型粒子结合.
- C1q和C4BP可以减少病毒与宿主细胞的结合和转导.
- 用C1q和C4BP治疗降低了包括IL-1β,IL-8,IL-6,TNF-α,IFN-α和RANTES在内的促炎性细胞因子和化学因子的mRNA水平.
- C1q和C4BP治疗减少了SARS-CoV-2伪型感染介导的NF-κB激活.
结论:
- 当地产生的C1q和C4BP可独立于补体激活,对SARS-CoV-2感染提供保护.
- 这些蛋白质抑制病毒与宿主细胞的结合,并减弱炎症反应.
- C1q和C4BP代表了管理SARS-CoV-2感染的潜在治疗点.
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