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Irradiation accelerates SARS‐CoV‐2 infection by enhancing sphingolipid metabolism

Authors :
Zhuanzhuan Wei
Yiyi Jiang
Gaomei Zhao
Chenwenya Li
Songling Han
Yin Chen
Tao Wang
Tianmin Cheng
Junping Wang
Cheng Wang
Source :
Journal of Medical Virology. 95
Publication Year :
2022
Publisher :
Wiley, 2022.

Abstract

Cancer patients who receive radiotherapy have a high risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of cancer cells to SARS-CoV-2 using S pseudovirions and probed the underlying mechanism via RNA-seq and other molecular biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion infection. Mechanistically, irradiation induced the expression of acid sphingomyelinase (ASM), which catalyses the hydrolysis of sphingomyelin to ceramide, contributing to lipid raft formation and promoting SARS-CoV-2 invasion. Inhibition of lipid raft formation with methyl-β-cyclodextrin (MβCD) or the tyrosine kinase inhibitor genistein and ASM suppression through small interfering RNA or amitriptyline (AMT) treatment abolished the enhancing effect of irradiation on viral infection. Animal experiments supported the finding that irradiation promoted SARS-CoV-2 S pseudovirion infection in A549 cell tumour-bearing BALB/c nude mice, whereas AMT treatment dramatically decreased viral infection. This study discloses the role of sphingolipid metabolism in irradiation-induced SARS-CoV-2 infection, thus providing a potential target for clinical intervention to protect patients receiving radiotherapy from COVID-19.

Subjects

Subjects :
Infectious Diseases
Virology

Details

ISSN :
10969071 and 01466615
Volume :
95
Database :
OpenAIRE
Journal :
Journal of Medical Virology
Accession number :
edsair.doi.dedup.....57b8ebea14b1893064eee3d2b25026ce
Full Text :
https://doi.org/10.1002/jmv.28266