Figure 2.

Intracellular pathways involved in the oncolytic activity of NDV and Influenza A Viruses. (A) Schematic of viral RNA sensing by NLRP-3 nod-like receptors and RIG-I-like receptors in the cytosol as well as TLR7/8 in endosomes containing viral RNA. Detection leads to activation of NF-kβ and IRF3 and translocation of these transcription factors to the nucleus, followed by production of type 1 interferons and proinflammatory cytokines. (B) In addition to RIG-I, IAV viral RNA could be sensed by the RLR Melanoma Differentiation-Associated gene 5 (MDA-5), and by TLR3/7. (C) Viral RNA sensing mediated by a DAI (DNA-dependent activator of IFN-regulatory factors) sensor, leading to activation of RIPK-3 and downstream MLKL (mixed lineage kinase domain-like pseudokinase) and resulting in cell death pathways such as necroptosis and apoptosis. (D) Illustration of viral response inhibition mediated by the NS1 gene of IAV. In the absence of NS1, activation of PKR, RIG-I, and IRF3 leads to upregulation of pathways necessary for antiviral response.