Fig. 7: E-regulates UcPS and inflammation in MHV-infected mice.

a mIL1β-FLAG secretion and Caspase-3 cleavage in HEK293T-mCC1a cells infected without or with MHV-A59 for 36 h at a MOI of 0.005, 0.05 and 0.5. b, c mIL1β secretion in MHV-A59 (MOI 0.1, 36 h) infected BMDMs from WT, TMED10 KO (b) or GSDMD KO (c) mice. d mIL1β secretion in MHV-A59 (MOI 0.1, 36 h) infected BMDMs in the presence of GFP or GFP-ECT. e Co-IP using HEK293T cells with TMED10-V5 and Myc-tagged E-MHV in the absence or presence of GFP or GFP-ECT. f mIL1β secretion in MHV-A59 (MOI 0.1, 36 h) infected BMDMs in the absence or presence of 10 μM UPA or Progesterone. g Co-IP using HEK293T cells with TMED10-V5 and Myc-E-MHV in the absence or presence of 10 μM UPA or Progesterone. h–k, IFNAR-KO mice injected with AAV-GFP or AAV-GFP-ECT were infected with MHV-A59 for 4 days and euthanized. Expression of GFP or GFP-ECT in the lung was verified by IF (j, upper panel). Serum IL1β levels were determined by ELISA (h). IL6 mRNA levels in indicated tissues was analyzed (i). Lung inflammation was analyzed by H&E staining (j, middle and lower panel) and inflammatory area was quantified (k). l–o IFNAR-KO mice infected with MHV-A59 were intraperitoneal injected with DMSO, 1 mg/kg UPA or Progesterone and euthanized. Serum IL1β levels were determined by ELISA (l). IL6 mRNA levels in indicated tissues were analyzed in (m). Lung inflammation was analyzed by H&E staining (n) and inflammatory area was quantified in (o). p A model for E-regulated UcPS. In brief, E proteins of the severe symptom coronaviruses (SARS, SARS2 and MERS) interact with TMED10 to activate the THU (TMED10-channel unconventional protein secretion)-mediated release of inflammatory cytokines. Data are mean ± s.d. Statistical significance was assessed using two-tailed t test (n = 5) (h, i, k), one-way ANOVA (n = 5) followed by Tukey’s multiple-comparison test (l, m, o). P values are indicated. Scale bars, 50μm. Source data are provided as a Source Data file.