ISG15 and infection: Sample separation across the first principal component was predominantly driven by the acute induction (upregulation) of specific genes in the panel following infection (Supplemental Figure S7A); these included known IRF3-target genes Rsad (viroporin), Cxcl10, IFN-b, Isg15, Ifi44, and Ifit2 [34] and ISGs including Mx1, Mx2, Isg20, Oas1b, and others; parallel induction of Tnfa, IL6 and IL-1 was also detected.