A study from the lab of Professor Richard Hardy and collaborators at University of Louisville Medical School and University of Colorado Medical School has established a link between alphavirus RNA stability, mediated by binding of a viral protein, and viral pathogenesis. The study published in PLoS Pathogens identifies new means by which to attenuate this important group of pathogens in order to develop novel vaccines.
Alphaviruses can cause significant disease in infected individuals; however, our understanding of the molecular interactions that enable infection and contribute to the development of disease is limited. The work detailed in this manuscript characterizes the interaction of a viral RNA-binding protein, Capsid, with the viral genomic RNA. Importantly, these interactions were found to be at specific sites on the genome but not essential for virus assembly. Mutation of the capsid/RNA interaction sites decreased the replication of the virus and the severity of disease in a mouse model of infection. Taken together, these findings identify a previously undiscovered determinant of disease severity, and provide a potential basis for the development of new vaccines.
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