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

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

A rapid inhibition of RNA synthesis is observed in host cells infected by picornaviruses, which is mainly attributable to picornaviral 3C pro cleavage of DNA-dependent RNA polymerases. It has been demonstrated that PV 3C pro enters the nucleus via precursors and induces the cleavage of TATAbinding protein-associated factor 110 (TAF110), TATA box binding protein (TBP), cAMP response element-binding protein-1 (CREB-1), octamer binding protein-1 (Oct-1), p53 and transcription factor IIIC (TFIIIC) to shut off host cell transcription [49] [50] [51] [52] [53] [54] (Table 1 ). In addition to these transcriptional factors associated with RNA polymerase, FMDV 3C pro can also interrupt transcription by cleaving nuclear histone H3, and EV71 3C pro can also cleave CstF64 of the polyadenylation machinery [55, 56] . Replication of the host cell occurs in the nucleus, whereas replication of the virus occurs in the cytoplasm. Furthermore, 3C pro interferes with the expression of host genes by inhibiting transcription and cap-dependent translation to provide cellular resources for viral replication. [46] . The a, b, c and d subelements form the cloverleaf structure. And the 3'NCR of RNA consists of two stem-loops (X, Y).There are three structures that can interact with 3C pro and its precursor: namely the 5 1 cloverleaf (5 1 CL), cis-acting RNA elements (cre), and the 3 1 NTR poly (A). The ribonucleoprotein (RNP) complexes formed by the binding of 3CD to stem-loop d of 5 1 CL and the binding of PCBP/3AB to stem-loop b are necessary for viral RNA replication. The cre hairpin of PV located in 2C ATPase can interact with 3B, 3D pol and 3CD to initiate RNA synthesis. The PABP bound to the poly (A) tail interacts with RNP for RNA replication.