How the presence of virus acts on innate immune system components, i.e. interferons, activating the Jak-Stat pathway. Double-stranded RNA, the product of viral replication, is recognized by interferons α, β, and γ and they in turn (especially α and β) activate PKR. See Fig. 5 for PKR actions. Interferons also activate MXA and MXAB which block transcription of viral products by the viral polymerase, and activate 2'-5' OAS 1 & 2, which inhibit viral protein synthesis and stimulate apoptosis. However Tag may block the actions of 2'-5'OAS 1 & 2 by initiating transcription of inhibitors of apoptosis genes (see small orange sunburst block). Interferon α, EGF, and IL-6 activate Jak-Stat pathways, activating Stat1 which becomes phosphorylated and binds p48 and Stat2 (the trimer is ISGF3 or STAT1), bind to the ISRE on DNA and initiate transcription of IFN-inducible genes (one of which is IL-6, see large orange sunburst box). Stat1 also binds SP1 and this dimer initiates transcription of NCAM1, a cell adhesion molecule. Genes colored in yellow-orange denote altered gene expression levels measured.