Picornaviral processing: some new ideas

Abstract

Mature picornaviral proteins are derived by progressive, post-translational cleavage of a giant precursor polyprotein. At least three viral-encoded proteolytic activities are involved in the processing. The first cleavage takes place while the polyprotein is still nascent on a ribosome. In poliovirus, this event is probably catalyzed by peptide 2A, a protein from the middle portion of the genome. Most subsequent processing is effected by viral protease 3C, a thiol-type enzyme, responsible for eight to ten self-cleaving and autocatalytic reactions within the polyprotein. The final proteolytic processing event, maturation of the VPO peptide, may occur by a novel, autocatalytic, serine-type mechanism, where viral RNA serves as proton-acceptor during the cleavage reaction.