Figure 3.

Regulation of type I IFN due to the activation of Toll-like receptors. Upon activation of Toll-like receptor (TLR) induced directly by viruses, different pathways can be activated. TLR7 recognize ssRNA, promoting the binding with MYD88, that will later interact with TRAF6, activating IRF7 which is translocated to the nucleus where it binds to DNA, promoting the release of IFN-α/β. TLR3 recognize dsRNA, promoting the interaction with TICAM-1 and TRIF, that activates AP-1, NF-κB, and IRF3, which are translocated to the nucleus, where they bind to DNA, promoting the release of IFN-β. The dsRNA can activate an alternative pathway, which can be sensed by either retinoic acid-inducible gene I (RIG-I) or by melanoma differentiation-associated protein 5 (MDA5). These receptors activate mitochondrial antiviral-signaling protein (MAVS), and by doing so they promote the IRF3 and/or IRF7 activation, and later translocation into the nucleus where they bind to DNA, promoting the release of IFN-α/β. There are two ways of activating TLR9, one is through the recognition of a type A CpG-DNA, which activates the pathway mediated by MYD88, similar to TLR7, while the other one involves the recognition of a type B CpG-DNA, where TLR9 binds with MYD88, activating IRF1, which is then translocated into the nucleus where it binds to DNA promoting the release of IFN-β. On the other hand, TLR4 is able to recognize viral peptides, activating a MYD88 -depending pathway similar to TLR7.