Fig. 1: Type I interferon signaling restricts SARS-CoV-2 infection of the lungs of mice.

a Schematic representation of SARS-CoV-2 inoculation schedule. Several wild-type (WT) and knockout mouse strains were inoculated intranasally with 2 × 105 TCID50 of passage 4 (P4) SARS-CoV-2. On the indicated days post inoculation (p.i.), lungs were collected for determination of viral RNA levels and scored for lung damage. b, c Normalized viral RNA levels in the lungs of BALB/c WT (blue circles, n = 3) and SCID (red circles, n = 3) mice and C57BL/6 WT (blue circles, n = 5), Ifnar1−/− (day 2 p.i. (red circles, n = 3), day 3 p.i. (red circles, n = 8), day 3 p.i. inactivated SARS-CoV-2 (red triangles, n = 4), day 4 p.i. (red circles, n = 3)), and Il28r−/− (purple circles, n = 5) mice. At the indicated time intervals p.i., viral RNA levels were determined by RT-qPCR, normalized against β-actin mRNA levels and transformed to estimate viral genome equivalents (vge) content per weight of the lungs (Supplementary Fig. 2). For heat inactivation, SARS-CoV-2 was incubated for 30 min at 56 °C. Dotted line indicates lower limit of quantification (LLOQ). The data shown are means ± SEM. d Histopathological scoring of the lungs for all different mouse strains. Mice were sacrificed on day 3 p.i., and the lungs were stained with H&E and scored for signs of lung damage (inflammation and hemorrhage). Scores are calculated as percentage of the total maximal score. “No score” means not contributing to theoretical full cumulative score of 100%. Numbers (n) of animals analyzed per condition are given in the inner circle. e Heatmap showing gene expression profiles of 30 selected marker genes in the lungs of uninfected and infected Ifnar1−/− mice (n = 3 per group). Analysis performed on day 3 p.i. The scale represents fold change compared to non-infected animals. Statistical significance between groups was calculated by two-tailed Mann–Whitney U test (b) or by Kruskal–Wallis with two-sided Dunn’s post hoc test (c). P values: **P = 0.0013, *P = 0.035 (c); ns not significant.