ISG15 and infection: At 24 h after infection, HPAI H5N1/483 tended to induce higher mRNA levels of IFN-β, IFN-λ1, CCL5, CXCL10, TNFα, IL-6, ISG15, and MX1 than most HPAI H5N6/H5N8 avian isolates in human airway organoids and in alveolar epithelial cells (MOI 2); we observed statistical significance for IFN-λ1, CXCL10, and MX1 in human airway organoids and IFN-β, IFN-λ1, CCL5, CXCL10, ISG15, and MX1 in alveolar epithelial cells (Appendix 2 Figure 2).