Membrane Protein of SARS-CoV-2 Promotes the Production of CXCL10 and Apoptosis of Myocardial Cells.

SARS-CoV-2 infections directly or indirectly cause unconscionable vascular events, significantly increasing the morbidity and mortality of COVID-19. Biomarkers associated with cardiac injury often elevate in individuals with COVID-19. Cytokine storm is a mechanism underlying myocardial cell injury caused by SARS-CoV-2 infections. Cell apoptosis in AC16 cells overexpressing structural and helper proteins of SARS-CoV-2 was detected by Western blot, MTT and TUNEL assay. The M protein was determined to play the most pronounced role in inducing apoptosis. Transcriptome sequencing on AC16 cells overexpressing the M protein was performed to screen differentially expressed genes (DEGs), which were further subjected to the gene set enrichment analysis. The regulatory effect of CXCL10 on cell apoptosis of AC16 cells overexpressing M protein was finally explored. Overexpression of M protein significantly increased the Bax/Bcl-2 and cleaved caspase-3/caspase-3(CC3/C3) ratios and the percentage of TUNEL-positive cells in AC16 cells, while markedly reducing cell viability. CXCL10 was the most prominent DEG in AC16 cells overexpressing M protein. Knockdown of CXCL10 partially reversed the increases in the Bax/Bcl-2 and cleaved caspase-3/caspase-3 ratios, the percentage of TUNEL-positive cells, as well as the release of pro-inflammatory cytokines in AC16 cells overexpressing M protein. The M protein of SARS-CoV-2 triggers the production of CXCL10 and apoptosis of myocardial cells.