诱导性CD147上调增强了延长的SARS-CoV-2感染,引发了严重的COVID-19,独立于ACE2
Ke Wang1,2, Peng Lin1,2, Ruo Chen1,2
1Department of Cell Biology of National Translational Science Center for Molecular Medicine and Department of Clinical Immunology of Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Signal transduction and targeted therapy
|February 2, 2026
概括
严重的COVID-19病原体包括CD147上调,增强病毒感染和免疫失衡. 一种抗CD147抗体Meplazumab有效抑制SARS-CoV-2的进入并恢复免疫平衡.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 由于高死亡率,严重的COVID-19带来了重大的公共卫生挑战.
- 严重的COVID-19病例的确切病原体仍然不完全理解.
研究的目的:
- 为了阐明CD147在严重的COVID-19病变发生过程中的作用.
- 研究SARS-CoV-2尖端蛋白与CD147.7之间的相互作用.
- 为了评估抗CD147抗体Meplazumab的治疗潜力.
主要方法:
- 对感染病毒的 rhesus 的肺组织进行分析.
- 研究转录因子阿里碳水化合物受体 (AhR) 在CD147表达中的作用.
- 低温电子显微镜 (cryo-EM) 用于确定CD147尖端复合物的结构.
- 在体外和体内评估梅普拉祖马布的疗效.
主要成果:
- 在肺中,SARS-CoV-2感染对CD147进行上调和对膜结合的ACE2进行下调,促进病毒传播和严重的病变.
- 亚利碳化合物受体 (AhR) 途径介导SARS-CoV-2诱导的CD147上调.
- 观察到免疫失衡,包括T细胞和B细胞死亡以及M2巨细胞的改变.
- 梅普拉祖马布治疗抑制了病毒的进入,降低了细胞因子水平,恢复了免疫平衡.
- 冷-EM结构揭示了CD147和SARS-CoV-2尖端蛋白之间的五个关键相互作用残留物,这些残留物是Meplazumab可以准的.
结论:
- CD147上调是严重COVID-19病原发生的关键因素,导致病毒感染延长和免疫失调.
- 针对CD147尖端蛋白与梅普拉祖马布的相互作用,为严重的COVID-19提供了一个有前途的治疗策略.
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