Extended Data Fig. 5: Orf6 expression is a major determinant of enhanced innate immune antagonism by emerging VOCs.

(a) IFNβ and CXCL10 secretion from infected Calu-3 cells measured at 48hpi, replicate measurements from one of two independent experiments shown. (b) Quantification of IRF3 nuclear translocation in Calu-3 cells infected with Alpha WT and Alpha ΔOrf6 detected by single-cell fluorescence microscopy over time. Data from 1500 cells/condition are shown. (c) Viral replication in the presence or absence of 5 μM ruxolitinib (Rux) at 48hpi in cells from Fig. 3c. One representative of three independent experiments shown. (d) HAEs were infected with 1500 E copies/cell of the indicated variants in the presence or absence of 5 μM ruxolitinib. Intracellular E copies from three biological replicates are shown. Apical washes are shown in Fig. 3f–h. (e, f) Infection of HAEs with BA.5 WT or BA.5 ΔOrf6 with 1500 E copies/cell showing (e) viral release into apical washes over time or (f) IFNB and CXCL10 normalized to GAPDH at 72hpi. Three biological replicates shown. For a, c-f mean + /-SEM or independent datapoints are shown. For b, box and whisker blots show 10–90 percentile and groups were compared at each time point as indicated using a Kruskal-Wallis test. For c, groups were compared by an unpaired two-tailed Student’s t-Test. For d and f, one-way ANOVA with a Bonferroni post-test was used. For e, two-way ANOVA and Bonferroni post-test was used.

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