Positive-sense RNA viruses represent a diverse group of economically and medically important pathogens. The genomic RNA of these viruses is a multi-functional molecule that serves as an mRNA for translation of virus proteins and a template for the synthesis of a minus-sense RNA replication intermediate. In order to determine the means by which genome function is regulated this project focuses on Sindbis virus (the type species of the genus Alphavirus) minus-strand RNA synthesis programmed by the positive-sense genomic RNA and committed by the viral replicase. The long-term goal of the research is to develop an integrated model of Sindbis virus gene expression and genome replication. This project will investigate how RNA sequence elements at the 5' and 3' end of the Sindbis virus genome effect template recognition by the viral replicase, regulate template function, and facilitate productive initiation of minus-strand RNA synthesis. Using experimental systems established in the laboratory the research aims to: 1) map determinants in the 5' region of the genome and their cognate binding factors required for minus-strand RNA synthesis, and 2) elucidate the mechanism by which residues at the 3' end of the genome facilitate productive initiation of minus-strand RNA synthesis. Results from these studies will specifically impact the understanding of alphavirus gene expression and replication. Further, as single-stranded positive-sense RNA viruses are united by a common scheme of genome replication, principles established from these studies will have broader implications for this group of viruses generally. The project will involve the training of graduate students and a postdoctoral researcher. In addition, students from the university's program for underrepresented groups in the life sciences will be participants in this research project.
