Supplementary Figure 1: Ccp5^−/− and Ccp6^−/− mice display reduced antiviral activity against DNA viruses instead of RNA viruses.

(a) Knockout strategies for Ccp2–5 knockout mouse generation using CRISPR/Cas9 technology. The targeting exon was shown in upper panel and the knockout allele was sequenced in lower panel. (b) WT and Ccp knockout mice were intranasally inoculated with VACV (1×10⁶ pfu for each mouse), followed by survival curve calculation. n=10 for each strain. (c) Brains from the indicated mice intravenously injected with HSV (1×10⁶ pfu for each mouse) were homogenized on the indicated days, followed by viral titer examination. n=6 for each strain. (d, e) WT, Ccp5^−/− and Ccp6^−/− mice were intranasally inoculated with VACV (1×10⁶ pfu for each mouse), followed by analysis of serum IFNs through ELISA. n=6 for each strain. (f) Brains from WT, Ccp5^−/− and Ccp6^−/− mice intravenously injected with VACV (1x10⁶ pfu for each mouse) were homogenized on the indicated days, followed by viral titer examination. n=7 for each strain. (g–i) The indicated mice were intravenously injected with HSV (1×10⁷ pfu for each mouse), followed by RT-PCR analysis of Ifnb at the indicated times. Peritoneal macrophages, peripheral CD11c^high dendritic cells and lung fibroblasts were examined. n=7 for each strain. Data are shown as means±SD. ∗, P<0.01; **, P<0.001. Data are representative of at least three independent experiments.