Table 1.

Native immune response induced by HFMD-associated enterovirus nonstructural proteins.

Protein		Functions	Innate Immune Response	Re
EV-71	2A	Cleaves NLRP3 protein Cleaves IFN-α/β receptor 1(IFNAR1) Cleaves the nuclear pore glycoprotein protein 62 (Nup62) Slices mitochondrial antiviral signaling (MAVS) protein Reduces serine phosphorylation of signal transducers and activators of transcription 1 (STAT1)	Inhibits inflammasome activation Blocks IFN-induced Jak/STAT signaling Disrupts host nuclear transport pathways and alters nuclear permeability Inactivates the antiviral innate immune response of RIG-I Attenuates IFN-γ signaling	[46] [47] [48] [49] [50]
	2C	Interacts with the IPT domain of RelA(p65) Inhibits IKKβ activation	Reduces the formation of the predominant form of NF-κB(heterodimer p65/p50) Blocks NF-κB activation	[51] [52]
	3A	Interacts with the human β3 subunit of Na+/K+-ATPase (ATP1B3) protein,	Enhances the production of type-I IFN	[53]
	3C	Cleaves the TAK1/TAB1/TAB2/TAB3 Complex Cleaves gasdermin D and NLRP3	Suppresses cytokine expression Inhibits cell pyroptosis and NLRP3 inflammasome activation	[54] [55]
	3D	Binds to NLRP3 Decreases STAT1 expression	Activates NLRP3 inflammasome Attenuates IFN-γ signaling	[56] [32]
CA16	2C	Blocks the fusion of autophagosomes with lysosomes and triggers autophagosome accumulation	Induces autophagy	[57]
	3C	Binds to MDA5 and inhibits its interaction with MAVS	Blocks MDA5-triggered type I IFN induction	[58]
CA6	2C	Blocks the fusion of autophagosomes with lysosomes and triggers autophagosome accumulation	Induces autophagy	[59]
	3C	Binds to MDA5 and inhibits its interaction with MAVS	Blocks MDA5-triggered type I IFN induction	[60]
	3D	Binds to RIPK3	Induces RIPK3-dependent necroptosis	[61]
CB3	2A	Cleaves host protease ATG4A	Impairs autophagy	[62,63]
	3A	Binds to GBF1	interference with Arf1-mediated COP-I recruitment	[64]
	3C	Cleaves MAVS and TRIF	inhibits both the type I IFN and apoptotic signaling	[65]