Fig 2: The survival response of DVG-high cells is regulated by MAVS signaling. a, b SeV HD-infected A549 cells treated with either control-IgG, TNFR1 or TNFR2 neutralizing antibodies. a Percentage of active caspase-3 positive cells within the total cultures (n = 4). b Percentage of active caspase-3 positive cells within FL-high and DVG-high cells in each condition (n = 4). c, d A549 cells transfected with either control siRNA (si-Control) or TRAF1 siRNA (si-TRAF1) followed by SeV HD infection for 24 h. c Percentage of apoptotic cells within the total cell cultures (n = 3). d Percentage of active caspase-3 positive cells within FL-high and DVG-high cells in each condition (n = 3). e, f A549 CTRL and MAVS KO cells infected with SeV LD and HD (MOI = 1.5 TCID50 per cell) for 24 h. e Expression of surface TNFR2 was quantified by flow cytometry (n = 4) and f expression of cellular TRAF1, BIRC3, and TNFAIP3 (A20) mRNA by RT-qPCR. Data are expressed as copy number relative to the housekeeping gene GAPDH (n = 4). g–j A549 cells treated with control IgG (IgG) or TNFR2 neutralizing antibodies (TNFR2) during SeV HD infection were sub-cultured (SC) for 28 days. g Illustration of the experiment schedule. h Bright field images 18 days post SeV HD infection. One representative field from each treatment is shown. Magnification: ×20. Scale bar = 20 µm. i Total cell numbers during the infection time course. j Percentage of FL-high cells quantified by RNA FISH-FLOW 28 days post infection. Experiments were repeated twice and one representative experiment is shown. k Schematic representation of proposed model. DVGs-high cells engage a MAVS-dependent antiviral pathway that drives the antiviral response and the apoptosis of neighboring cells through the production of TNFa (denoted 1), while protecting the cytokine-producing cell from death through a TNFR2/TRAF1 mediated mechanism (denoted 2). Data are shown as ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 by one-way (a) or two-way (b, d, e, f) ANOVA with Bonferroni’s post hoc test, or unpaired t-test c. ns, non-significant. See also Supplementary Fig. 6