ISG15 and viral infectious disease: Double knockout (dKO) UbE1L–/– and ISG15–/– C57BL/6J mice with 6 and 9 days old infected with CHIKV exhibited increased levels of pro-inflammatory cytokines and chemokines, correlating to human cytokine and chemokine profile, and also showed increased lethality rate to viral infection (Werneke et al., 2011).