It seems that most viruses studied so far have developed a strategy to counteract the host innate immune system [13] . Two Nairoviruses (CCHFV, DUGV) have been shown to be inhibited by MxA, a protein induced by type I IFNs [19, 20] . Since the viruses are inhibited by IFN-induced proteins, viral virulence will depend at least in part on the ability of the virus to avoid or block the type I IFN response, and it is therefore very likely that Nairoviruses have developed tactics against this host defence mechanism. The current knowledge on how Nairoviruses manipulate the host innate immune system comes mostly from studies with CCHFV. Andersson et al. have shown that CCHFV showed a markedly delayed type I IFN response in cell culture, up to 48 hours after infection, possibly by interfering with the pathway that leads to activation of interferon regulatory factor 3 (IRF3) [21] . In addition they found that CCHFV is insensitive to IFNa treatment applied six hours post-transfection. One possible explanation for the delay in the IFN response is given by another study showing that CCHFV has developed a mechanism to remove the 59-terminal triphosphate group from its genome segments, thereby avoiding retinoic acid inducible gene I protein (RIG-I)-dependant IFN induction [22] . Another possible explanation may be the activity of the ovarian tumour-like (OTU) domain found in the amino-terminus of the viral L protein. Sequence analysis of the L proteins of Nairoviruses identified this domain, which represents a unique class of deubiquitinating enzymes (DUBs) [23] . Recent studies with the CCHFV OTUcontaining L protein showed that it decreases the coupling of ubiquitin (Ub) and the ubiquitin-like protein (Ubl) encoded by interferon stimulated gene 15 (ISG15) to cellular proteins [24] . The post-translational modification of proteins by Ub and Ubls regulates essential processes in the type I IFN response to viral pathogens [25, 26] . Cellular DUBs have been found which appear to act as part of negative feedback control systems for IFN induction pathways [27, 28] . Removal of Ub and/or ISG15 from their protein conjugates will disrupt a number of elements of the IFN induction pathway, and targeting the ISG15 and/or the ubiquitin system is a common strategy used by different viruses to inhibit innate immune responses [29, 30, 31, 32] .