It is interesting to note that the extent of transcript upregulation in the V/HFs compared to the primary HFs varied from gene to gene, suggesting that some transcripts (IFIT1, IFIT2, IFIT3) were upregulated to the same extent in the presence or absence of interferon signaling whilst for others (CXCL10, MX1, Mx2 and ISG15) both IFN-independent and dependent mechanisms contribute to maximal upregulation during infection. The gene discussed is ISG15; the disease is infection.