Differences were seen in the effectiveness of the different OTU-containing fragments of the GV L to block IFNa-or IFNcinduced gene transcription when expressed in our reporter genebased studies. GV L1-169 and L1-667 reduced the transcriptional activity induced by IFNa or IFNc to 30% and 40% respectively of the positive control, whereas the protein L1-1757 was less effective in reducing the transcriptional activity of the Mx-1 promoter or the GAS promoter (55% and 65% of the positive control respectively). These differences might reflect slight differences in the amounts of protein expressed in the transfected cells that cannot be detected by immunoblotting. Alternatively, the catalytic domain of the NSDV L protein might be autoinhibited by folding or oligomerisation in the longer construct L1-1757, in contrast to the shorter versions containing the OTU domain. A similar observation was made with the OTU domain containing nonstructural protein 2 (nsp2) from porcine reproductive and respiratory syndrome virus where a longer fragment was less effective in blocking NFkB promoter activity than a smaller version of this protein [30] . In addition it has been shown that CCHFV full length L displayed significantly less DUB activity than shorter versions of the protein [24] . Further crystal structures to extend that of the basic OTU domain [44, 45, 58] will clarify these points.