The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation

To replicate in vivo, viruses must circumvent cellular antiviral defense me chanisms, including those induced by the interferons (IFNs). Here we demons trate that simian virus 5 (SV5) blocks IFN signalling in human tells by inh ibiting the formation of the IFN-stimulated gene factor 3 and gamma-activat ed factor transcription complexes that are involved in activating IFN-alpha /beta- and IFN-gamma-responsive genes, respectively. SV5 inhibits the forma tion of these complexes by specifically targeting SV5, a component common t o both transcription complexes, for proteasome-mediated degradation. Expres sion of the SV5 structural protein V, in the absence of other virus protein s, also inhibited IFN signalling and induced the degradation of STAT1. Foll owing infection with SV5, STAT1 was degraded in the absence of virus protei n synthesis and remained undetectable for up to 4 days postinfection, Furth ermore, STAT1 was also degraded in IFN-pretreated cells, even though the ce lls were in an antiviral state. Since pretreatment of cells with HIV delaye d but did not prevent virus replication and protein synthesis, these observ ations suggest that following infection of IFN-pretreated cells, SV5 remain s viable within the cells until they eventually go out of the antiviral sta te.