Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells

Sun, Di; Chen, Shun; Cheng, Anchun; Wang, Mingshu

Except for the cleavage of NEMO by 3C pro [116] , the L pro of FMDV is also associated with the degradation of p65/RelA and decrease in IRF3/7 expression to suppress the immune response [117, 118] . Subsequently, a study has shown that 3C pro induces the degradation of karyopherin α1 (KPNA1) to antagonize interferon via the JAK-STAT signaling pathway by blocking the nuclear translocation of STAT1/STAT2 [119] . In CV, 3C pro exhibits the capability of cleaving the proline-rich region of MAVS and two terminal domains of TRIF to escape host immunity ( Figure 6 ) [120] . transmembrane domain of 3A are both necessary for the proteolysis of MAVS [112, 113] . For another precursor, HAV 3CD protease-polymerase disrupts TLR3 signaling by degrading TRIF (Figure 6 ) and this degradation is not dependent on only the protease activity of 3C pro but also requires the 3D sequence to modulate the substrate specificity of 3C pro [114] . NEMO, a bridging adaptor protein for the activation of NF-κB, is another substrate of HAV 3C pro at the Q304 residue [115] . NEMO is also cleaved by FMDV 3C pro at the Gln-383 residue but not by the 3C pro of EV 71 [116] . Except for the cleavage of NEMO by 3C pro [116] , the L pro of FMDV is also associated with the degradation of p65/RelA and decrease in IRF3/7 expression to suppress the immune response [117, 118] . Subsequently, a study has shown that 3C pro induces the degradation of karyopherin α1 (KPNA1) to antagonize interferon via the JAK-STAT signaling pathway by blocking the nuclear translocation of STAT1/STAT2 [119] . In CV, 3C pro exhibits the capability of cleaving the proline-rich region of MAVS and two terminal domains of TRIF to escape host immunity ( Figure 6 ) [120] . In addition to viral and host proteins, microRNAs (miRNAs) is also involved in posttranscriptional gene expression regulation and it has been confirmed that miRNAs play significant roles in the interaction between virus and host. The 3C pro of EV71 downregulates miR-526a to suppress the RIG-I-dependent innate immune response [121] .