Cul3 and Klhl9 are required for IFNγ-induced inhibition of norovirus replication in BV-2 cells. (A) Viability assay of non-clonal BV-2-Cas9 knock-out cells transduced with non-targeting (NT) sgRNAs or sgRNAs targeting Cul1, Cul2, Cul3, Cul4A, Cul4B, and Cul5 as described in Fig. S1; percentage of the wild-type allele present in the non-clonal cell knock-out pool. (B and C) Plaque assay of WT, Cul3−/−, Klhl13−/−, Klhl19−/−, Klhl20−/−, and Klhl22−/− BV-2 clonal knock-out cells as described in Fig. S1. (D) Viability assay of non-clonal BV-2-Cas9 knock-out cells transduced with NT sgRNA or sgRNA targeting Klhl9 as described in Fig. S1; percentage of the wild-type allele present in the non-clonal cell pool provided. Values in (A–D) represent means ± SEM from 2 to 3 independent experiments. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, and ****P ≤ 0.0001 were considered statistically significant. ns, not significant. P value was determined by two-way ANOVA with Dunnett’s multiple comparison test.