CORONAVIRUS RNA TRANSCRIPTION--VIRUS-HOST INTERACTION

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DESCRIPTION (adapted from investigator's abstract) Coronaviruses are enveloped RNA viruses that cause a variety of diseases in humans and animals. Coronavirus RNA transcription involves interactions between the leader RNA and the intergenic sequences (IGS) where subgenomic mRNA synthesis is initiated. It has been proposed that the leader-IGS interaction is mediated by direct RNA-RNA interactions between complementary sequences. Using a mutant of mouse hepatitis virus (MHV) called JHM2c, a subset of subgenomic mRNA species were found that resulted from initiation at various sites in the IGS where no sequence complementarity to the leader exists. This lead to the hypothesis that protein-RNA and protein-protein interactions, rather than RNA-RNA interactions are the driving force for the initiation of mRNA transcription. The heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is a potential cellular factor involved in the regulation of MHV RNA transcription and experiments to test the involvement of hnRNP-A1 in coronavirus transcription are proposed. The first aim will define the interactions between hnRNP-A1 and the cis-acting sequences of MHV RNA both in vitro and in vivo, and then determine the functional significance of this protein-RNA interaction in the regulation of MHV RNA transcription. The second aim will characterize the interactions between hnRNP-A1 and the MHV RNA polymerase and nucleocapsid proteins, and then determine the functional significance of these protein-protein interactions in the regulation of MHV RNA transcription.