Processing Determinants and Functions of Cleavage Products of Picornavirus Polyproteins

Picornaviruses employ a number of unique intracellular mechanisms and novel processes during their infectious cycles resulting in their being among the most successful of viral pathogens. This chapter begins with a discussion of the features of viral proteinases, continues with an outline of the functions of both precursor and mature viral polypeptides present during a picornaviral infection, and concludes with a brief summary of nonviral substrates cleaved by viral proteinases. Viral proteinases including L protein, 2A proteinase and 3C proteinase have been discussed in the chapter. The aphthoviruses and cardioviruses code for an L protein at the N terminus of their polyproteins. The cleavage activity of the L proteinase from foot-and-mouth disease virus (FMDV), an aphthovirus, has been well characterized. The 3C proteinase activity carries out the majority of the proteolytic processing of the viral polyprotein. The evolution of picornaviruses might dictate that the P1 to PN substrate positions be identical or similar to optimize polyprotein processing and maximize the generation of mature viral proteins. In vitro synthesized viral RNAs containing large inframe deletions within the P1 region are self-replicating in cultured cells, suggesting that the proteins required for viral RNA replication are located primarily within the P2 and P3 (nonstructural) regions of the genome. Since picornaviruses utilize a mechanism of translation that is cap independent, it is advantageous to the virus to inhibit nonessential cap-dependent cellular translation.