Induction of type I interferon by RNA viruses: cellular receptors and their substrates

Baum, Alina; García-Sastre, Adolfo

To date 13 mammalian members of this family have been recognized as receptors involved in recognition of conserved microbial PAMPS (Akira and Hemmi 2003; Janeway 1989 ). These receptors are composed of an extracellular leucine-rich repeat domain which participates in pathogen recognition, and a conserved cytoplasmic domain with homology to IL-1R which is involved in downstream signaling through MyD88 or TRIF adaptor proteins (Akira and Takeda 2004) . The extracellular domains of TLRs exhibit high structural diversity and have been shown to recognize a wide variety of pathogens including bacteria, fungi, protozoa, and viruses. Whereas TLRs responsible for bacterial and fungal recognition are located on the cell surface, those responsible for sensing viral infections are commonly located intracellularly in endosomal compartments (Diebold 2008) . Upon activation, TLR3 and TLR7/8 initiate a signaling cascade though adaptors TRIF and MyD88, respectively, leading to expression of IFN and proinflamatory cytokines .