The virus had a stronger effect on IFNa-induced STAT1 phosphorylation than on STAT2 phosphorylation at all times, suggesting that STAT1 is the primary target. As with the block of IFN induction, the blockade of both type I and type II IFN actions mapped to the OTU domain of the L protein and required a functional OTU catalytic site. So far no definitive role for ubiquitination or ISG15ylation in type I or type II IFN signalling has been shown. JAK1 and STAT1 have been shown to be conjugated by ISG15 [60, 61] ; however, STAT1 phosphorylation in response to IFN is normal in cells from ISG15 knock-out mice [62] , suggesting that ISG15 plays no role in the immediate cell response to IFN.