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

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

Taken together, 3C pro and the precursors exhibit essential functions in viral replication. Does proteinase activity or RNA-binding activity of the 3C domain stimulate RNA synthesis? There are three distinct regions within 3C pro : the N-terminal region (K12 and R13), a central region (KFRDI86) and the C-terminal region (T153, G154 and K155) [43, 44] . Mutation (R84S/I86A) within the 3C-binding region of PV prevents stimulation of virus synthesis [45] and mutation (K12N/R13N) within the 3Cbinding region results in normal processing of viral translation but complete inhibition of (−)strand synthesis [34] . The mechanism by which 3C pro is involved in RNA synthesis is closely related to its RNA-binding activity. Although both 3C pro and 3CD can bind to viral RNA, there are differences. A [23, 28] . The release of mature and functional proteins from the polyprotein is dependent on primary and secondary cleavages and polyprotein processing differs slightly among diverse picornaviruses. In primary cleavage, L pro functions in apthoviruses by freeing itself (blue arrow), whereas the cleavage of P1-P2 is mediated by ribosome skipping in apthoviruses and cardioviruses (red triangle) [29] . The proteolytic 2A pro of enteroviruses is involved in primary cleavage and 3D pol cleavage to produce 3D' intermediate (red arrows). 3C pro and 3CD are responsible for a proportion of primary cleavages and almost all secondary cleavages (black arrow). The hepatovirus VP1-2A cleavage can be achieved by a host cell proteinase (green arrow). See the text for details.