Fig. 2.

Transcriptional activation of interferon alpha and beta: Type 1 interferon signaling may be stimulated by either cytosolic receptors or endosomal membrane receptors in the presence of double-stranded RNA (dsRNA), viral DNA, single-stranded RNA (ssRNA), or double-stranded DNA (dsDNA). Specific adaptor proteins bridge the receptor and the respective kinase. Upon kinase activation, IRF3 and IRF7 are phosphorylated by specific kinases and NFκB can be released from its inhibitory complex and translocate into the nucleus. Once IRF3 and IRF7 are phosphorylated, they form dimers. Dimerization partners are determined based on the site of phosphorylation and the levels of each protein. Once dimers form, they translocate into the nucleus and bind to the respective responsive element. IFNα has two viral response elements 30 kb apart (VRE1 and VRE2). VRE1 has preferential for IRF7 dimers whereas VRE2 has preferential binding for IRF3/IRF7 dimers but both are not necessary for full transcription [26]. IFNβ is preferentially transcribed by IRF3 and NFκB. IFNβ can further promote the activation of IFNα through stimulating the IFNAR receptor which produces increased levels of IRF7 (Fig. 1)