ISG15 uncut: Dissecting enzymatic and non-enzymatic functions of USP18 in vivo.

ABSTRACT

Posttranslational protein modification by ISG15 plays an important role in antiviral defense. We selectively inactivated the ISG15 isopeptidase activity of USP18 in mice. Increased ISGylation was accompanied by enhanced viral resistance without causing detrimental side effects suggesting that USP18 protease inhibition might be a suitable antiviral strategy.