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- Title
CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis.
- Authors
Tang, Zihan; Xu, Yanyan; Tan, Yun; Shi, Hui; Jin, Peipei; Li, Yunqi; Teng, Jialin; Liu, Honglei; Pan, Haoyu; Hu, Qiongyi; Cheng, Xiaobing; Ye, Junna; Su, Yutong; Sun, Yue; Meng, Jianfen; Zhou, Zhuochao; Chi, Huihui; Wang, Xuefeng; Liu, Junling; Lu, Yong
- Abstract
Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway. Conversely, the pharmacological blockade of CD36 or p38 notably attenuates human platelet activation induced by the E protein. Similarly, the genetic deficiency of CD36, as well as the pharmacological inhibition of p38 in mice, significantly diminishes E protein-induced platelet activation and thrombotic events. Together, our study reveals a critical role for the CD36-p38 axis in E protein-induced platelet hyperactivity, which could serve as an actionable target for developing therapies against aberrant thrombotic events related to the severity and mortality of COVID-19. Aberrant coagulation and thrombosis are associated with severe SARS-CoV-2 infection. Here, the authors show that the E protein are associated with coagulation disorders in COVID-19 patients and could directly enhance platelet activation and thrombosis through a CD36/p38 MAPK/NF-kB signaling axis.
- Subjects
BLOOD platelet activation; THROMBOTIC thrombocytopenic purpura; COVID-19; BLOOD coagulation disorders; THROMBOPOIETIN receptors; INTRAVENOUS therapy
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-40824-7