CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis
© 2023. Springer Nature Limited..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Nature communications - 14(2023), 1 vom: 21. Aug., Seite 5077 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tang, Zihan [VerfasserIn] |
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| Links: |
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| Themen: |
CD36 Antigens |
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| Anmerkungen: |
Date Completed 23.08.2023 Date Revised 19.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-40824-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361034113 |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Xu, Yanyan |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Peipei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yunqi |e verfasserin |4 aut | |
| 700 | 1 | |a Teng, Jialin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Honglei |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Haoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Qiongyi |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Xiaobing |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Junna |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Yutong |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Jianfen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Zhuochao |e verfasserin |4 aut | |
| 700 | 1 | |a Chi, Huihui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xuefeng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Junling |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Chengde |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Saijuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Tingting |e verfasserin |4 aut | |
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