Fig. 2: Aberrant methylation triggered by SARS-CoV-2 regulates multiple targets related to immune response and cell death pathways.

Heatmap of genes (P < 0.01, enrichment factor >1.5) related to the cell death (A) and immune response (B). Box plot (C) depicting the expression levels of CASP1, CASP5, DDX3X, TRIB1, IL17RB, and TLSP in patients with COVID-19 (20 severe and 19 mild patients) as compared with those in healthy controls (n = 20). And scatter plots revealed m6A enrichment of CASP1, CASP5, DDX3X, TRIB1, IL17RB, and TSLP in patients. D Total m6A levels of COVID-19 patients and healthy controls (n = 3). E The protein levels of candidate genes were detected by western blot in COVID-19 patients and healthy controls (HCs). F CASP1, CASP5, DDX3X, TRIB1, IL17RB, and TLSP expression levels in HuT 78 cells co-cultured with activated THP-1 cells were measured after being treated with S proteins separately for 0, 6, 12, and 24 h. HuT 78 cells were co-cultured with (Ctrl) or without (spike) spike proteins (50 ng/ml), and cell death was detected by apoptosis assay (G), quantitative analysis of positive signals was showed in (H), and the protein levels of cleaved–CASP3 were detected using western blot (I). CCK-8 assay (J) was applied to evaluate proliferation abilities of HuT 78 cells with spike stimulated or without spike. Data were shown as means ± SD (n = 3, *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001).