Figure 9. avSGs and innate antiviral responses.

Viral infections generate RNA with non-self-signatures such as a 5′-tri-phosphate or double-stranded structure (a). In the case of IAVÄNS1, PKR is critical for the formation of avSGs (b). Wild-type IAV inhibits formation of avSGs by the actions of the NS1 protein (c). Some other viruses may activate different eIF2á kinases, such as GCN2, PERK, and HRI, to produce functional avSGs (d). avSGs are composed of SG markers and other RNA-binding proteins including RLRs, antiviral proteins (PKR, OAS, and RNase L) and viral RNA. Within avSGs, viral RNA could be sensed by RLRs to trigger antiviral signaling (e). Activated RLRs recruit mitochondrial IPS-1 via CARD-CARD interactions (f). IPS-1 serves as another platform for TRAFs and protein kinases, TBK-1, IKKi and IKK complex, to activate target genes (g). The antiviral proteins are activated by viral RNA to block viral RNA synthesis and translation (h). Moreover, OAS-RNase L system may produce dsRNA to amplify the RLR signaling (i).