ΔMac1 induces increased IFN-I, IFN-III, and cytokine responses compared to WT SARS-CoV-2 in cell culture. Calu-3 (A) and A549-ACE2 (B) cells were infected with SARS-CoV-2 WT and ΔMac1 at an MOI of 0.1 PFU/cell, and total RNA was collected 48 hpi. IFN-β, IFN-λ, ISG15, and CXCL10 levels were determined by qPCR using the ΔCt method with primers listed in SI Appendix, Table S2 and normalized to HPRT mRNA levels. The data show one experiment representative of three independent experiments with n = 3 for each experiment. (C) Calu-3 cells were infected as described above, and cell lysates were collected at 48 hpi and protein levels of PARP14 and OAS3 were determined by immunoblotting. The data show one experiment representative of three independent experiments. (D) Quantification of immunoblots shown in C. The data are the combined results of three independent experiments.