CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis

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.

Pathway-enhanced Transformer-based robust model for quantifying cell types of origin of cell-free transcriptome

“…We performed Cohen’s d effect statistics on 25 million pathway pairs between case and control groups, selecting the top 100 pairs with the highest absolute Cohen’s d effect for pathway network analysis. We found that Regulation of Platelet Activation, which appeared most frequently among these differential pathway pairs, might influence many physiological processes related to severe COVID-19, consistent with previous reports[46–48]. Additionally, pathways such as Leukocyte Aggregation[49], Ras protein signal Transduction, and Positive Regulation of Myoblast Differentiation, which have been proven related to severe COVID-19, also showed high differences (Fig.…”

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

“…Altered expression of genes include CX3CR1 [666], S100A12 [667], CSF2 [668], MPO (myeloperoxidase) [669], CD5L [670], F11 [671], S100A8 [672], PGLYRP1 [673], VEGFD (vascular endothelial growth factor D) [674], CXCL11 [373], BPI (bactericidal permeability increasing protein) [675], CXCL10 [676], S100A9 [677], CXCR1 [678], CXCR2 [679], ABCA3 [680], CD36 [681], SHH (sonic hedgehog signaling molecule) [682], TLR3 [683], CLEC4D [684], CCR2 [685], NEK7 [686], TLR7 [687], CCRL2 [688] and CAV1 [689] accelerates pneumonia progression. CX3CR1 [666], CD177 [690], PF4 [691], FFAR2 [692], MPO (myeloperoxidase) [693], F11 [694], S100A8 [695], VEGFD (vascular endothelial growth factor D) [674], IL1A [696], BPI (bactericidal permeability increasing protein) [697], AQP4 [698], BDNF (brain derived neurotrophic factor) [699], CXCL10 [700], RNASE2 [701], FCGR3B [702], S100A9 [703], IL1B [704], CXCR2 [705], GPIHBP1 [294], CD36 [706], TRIB3 [707], PCSK9 [708], FGF2 [709], FASN (fatty acid synthase) [710], PNPLA3 [711], HSPA6 [712], VIP (vasoactive intestinal peptide) [713], TLR3 [683], ADRB1 [328], SPOCK2 [714], TLR8 [715], CCR2 [716], IFIT3 [717], NEK7 [718], TLR7 [687], EFNB2 [719], CAV1 [720], CR1 [721] and AQP5 [722] plays essential roles in viral respiratory diseases. Previous study confirmed that CX3CR1 [723], S100A12 [724], CD177 [725], PF4 [726], MPO (myeloperoxidase) [727], CD5L [728], F11 […”

Targeting Cysteine Oxidation in Thrombotic Disorders

“…This is further supported by the lack of bleeding disorder in CD36 deficient mice or humans. It would therefore be helpful to determine whether platelet NADPH oxidase activity supports CD36-mediated thrombosis in other oxidative stress-related conditions (e.g., in diabetes [74], infection [99]).…”