Fig. 5

Innate immune evasion by Enterovirus. ssRNA, dsRNA and various proteins of EVs during replication and translation can activate and escape innate immunity through different pathways. (1) Viral RNA is recognized by TLR3, TLR7, TLR8 and TLR9, and then activates TRAF, TRIF, MyD88 and their downstream linker molecules, causing phosphorylation of IRF3, IRF7 and NF-κB to translocate to the nucleus, and finally promote the secretion of interferons (IFNs). (2) 2A protease(pro) and 3Cpro are mainly recognized by RIG-I and MDA5, and bind to MAVS in mitochondria to activate TRAF3 and TRAF6. However, prior to signaling to IRF1, IRF3, and IRF7, host ncRNAs regulated by the virus target and inhibit the activation of TRAF, ultimately reducing IFNs production. (3) Binding of IFNs to the receptor IFNAR activates downstream JAK1 and Tyk2, which promotes the phosphorylation and translocation of STAT1 and STAT2 to the nucleus, initiating transcription of IFN-stimulated response elements (ISREs). However, this pathway is directly or indirectly inhibited by 3Cpro, 2Apro, and 2Bpro, resulting in decreased secretion of IFNs. (4) Assembly of the NLRP3 inflammasome requires the sensor NLRP3, the adaptor protein ASC, and pro-caspase-1. However, host-invading viruses can activate and inhibit the formation of the NLRP3 inflammatory complex. Solid line with arrows at the end indicates activation; dashed line with a small line at the end indicates inhibition; scissor indicates cutting