The RNA picornaviruses have become extraordinarily important and well studied models for experimental investigations into the molecular mechanisms of IRES-dependent translation, protein processing, viral RNA synthesis, virion assembly, virus-cell interactions and ultimately disease pathogenesis. Diverse cis-acting RNA elements, host protein requirements, antiviral drug sensitivity, and preferred polyprotein processing schemes suggest that core RNA replication pathways are not the same for all the members in this important family of viruses. The goal of the current project is to compare and contrast the requisite viral proteins, RNA binding steps and general processes of the cardiovirus RNA replication scheme with those from polio- and rhinoviruses and establish which of these steps are common and descriptive of the family as a whole. The effects of the inhibitory agent dipyridamole will be studied to establish the potential of this drug as an antiviral and as a research tool that can discriminate between translation and RNA replication. The regulatory role of cardioviral polyprotein precursors or processing intermediates in RNA synthesis will be established and compared to existing models for polio- and rhinoviruses. In order to catalogue the local structural components that contribute to cardiovirus specific template activity during RNA synthesis, the interaction between viral polymerase components and the 5' and 3' untranslated regions of the genome will be characterized.
These aims rely on existing reagents, assays, and technologies and their successful accomplishment is very likely to help establish new paradigms in the RNA replication field.
| Fata-Hartley, Cori L; Palmenberg, Ann C (2005) Dipyridamole reversibly inhibits mengovirus RNA replication. J Virol 79:11062-70 |
