We were unable to reconcile these data with the numerous reports ascribing a critical antiviral role to Isg15 during the infection of mice in vivo with multiple viruses (for example, chikungunya virus17, murine gammaherpesvirus 68 (ref. 14), IAV14, influenza B virus14, 33, Sindbis virus14, vaccinia16, HSV-1 (ref. 14) and murine norovirus18). This evidence concerns the gene ISG15 and infection.