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

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

the sequential cleavage of eIF4GI in BHK cells after infection with wild-type FMDV [62] . Two forms of eIF4A, namely, eIF4AI and eIF4AII, exist within mammalian cells. FMDV 3C pro cleaves only eIF4AI, which is not related to eIF4AII even though they share 91% sequence identity [63] . In addition, during PV, CVB3 and HRV infection, eIF5B eukaryotic initiation factor is cleaved at a single site (VVEQÓG), which separates the N-terminal domain from the conserved GTPase domain and C-terminal domain [64] . PCBP2, also known as hnRNP E2, has multiple functions in the post-transcriptional control of host and viral gene expression. The ability of PV to take advantage of PCBP2 in translation and replication has already been discussed [65] , and it has also been observed that PCBP2 is cleaved by 3C pro in HAV. Thus, HAV may regulate protein synthesis and RNA synthesis by 3C pro [66] . In addition to PABP cleavage by 2A pro and PV, HAV and EMCV 3C pro s have also been reported to specifically cleave PABP [67] [68] [69] . A study of EMCV 3C pro suggests that specific PABP cleavage is required for virus replication or that full-length PABP is not absolutely required for virus replication [69] . The cleavage of Ras GTPase-activating protein-binding proteins (G3BP1) may be induced by 3C pro to facilitate viral replication after CVB3 infection [70] . Recently, it has been demonstrated that the Sam68 nuclear RNA-binding protein can be cleaved by 3C pro of FMDV, thus allowing 3C pro to redistribute Sam68 to the cytoplasm. Remarkably, Sam68 can interact with the IRES in FMDV during infection, which then can translate viral RNA. Thus, it is speculated that Sam68 plays a supportive role in the virus life cycle [71] .