The Role of a Host Ion Pump in RNA Virus Recombination

Host - virus interactions are greatly affected by the exceptionally rapid evolution of the pathogen. Moreover, the host itself is a major player affecting virus evolution. Evolution of plusstranded RNA viruses is frequently driven by RNA recombination, a process that allows RNA viruses to overcome immunity, jump species and change viral pathogenicity in all types of living organisms. Viral recombination is also a major factor in emergence of new viruses, which is a continuing threat to our society. Therefore, studies on viral RNA recombination are critical to understand the effect of the host on the viral recombination process, which is currently unknown. The PI has developed efficient and highly tractable cel/-free, yeast and plant-based recombination assays, making Tomato bushy stunt virus (TBSV) the most suited for recombination studies among al/ plus-strand RNA viruses. Accordingly, to unravel the role of the host in viral RNA recombination, the PI's lab has made major progress by identifying host factors affecting RNA recombination for the first time based on genome-wide screens covering 95% of host genes. This proposal focuses on a key host factor affecting viral RNA recombination. The host factor is Pmr1p Ca2+/Mn2+ pump, which is a ubiquitous and conserved protein in eukaryotes. The human homologs of Pmr1p have been shown to play critical roles in genetic diseases, such as Hailey-Hailey Disease and Darier disease. In the absence of Pmr1p, the rate of TBSV RNA recombination is extremely high demonstrating the critical role of the host in viral RNA recombination. In order to characterize the role of Pmr1p in RNA recombination, the PI will use the advanced genetics tools available for plant and yeast, which is a model host, in combination with biochemical approaches.