Coxsackievirus B RNA replication: lessons from poliovirus.

The replication of coxsackievirus RNA occurs with rapid onset, starting approximately 2.5 h after infection. The mechanisms entailing the RNA replication of enteroviruses, like coxsackievirus and poliovirus, are highly conserved. These processes require two steps of RNA amplification: (i) complete synthesis of the negative-strand RNA using input RNA as the template and (ii) synthesis of the positive-strand RNA using the intermediate negative-strand RNA as the template. Successful enterovirus RNA replication requires all of the viral nonstructural proteins in their mature and precursor forms, as well as RNA secondary structures in the template. The encoded nonstructural proteins are responsible for RNA replication through multiple protein-protein interactions between viral and/or host proteins to mediate RNA synthesis, induce membranous vesicles, and deliver the replication complex to the template. The RNA secondary structures at the 5' and 3' termini of the template position the RNA replication complex at the initiation site(s) for both negative- and positive-strand RNA synthesis, thus providing binding sites for viral and host proteins that may functionally circularize the genome during RNA synthesis. Although considerable knowledge has been gained regarding the mechanism of enterovirus RNA synthesis, the complete steps in RNA replication have not been fully determined. The aim of this review is to summarize the current state of our knowledge and to present a model that encompasses the identified steps of enterovirus RNA replication.