Several other viruses have exploited this mechanism of negatively regulating the IFN induction by encoding proteases of the OTU family [24, 30, 53, 54] . All these proteases exert deconjugating activities towards ubiquitin or the ubiquitin-like (ubl) molecule ISG15 or both. Interestingly, cells themselves make use of DUBs to regulate the IFN pathway but, in contrast to nairoviral OTUs, cellular DUBs tend to have highly specific targets [27, 55, 56, 57] . For example, deubiquitinating enzyme A (DUBA) selectively cleaved polyubiquitin chains on tumor necrosis factor receptorassociated factor 3 (TRAF3) and was identified in a small interfering RNA-based screen as a negative regulator of type I IFN production [27] . The crystal structure of the CCHFV OTU domain revealed a unique structure allowing it to bind ISG15 as well as ubiquitin, and this ability to interact with both conjugating proteins is one of the underlying reasons for the promiscuous activity of the nairovirus OTUs [44, 45, 58] .