Suppression of Viral RNA Recombination By Host Genes

Rapid evolution if RNA viruses with mRNA-sense genomes is a major concern to human health and economic welfare due to the devastating diseases these viruses inflict on humans, animals and plants. Emergence of new pathogenic RNA viruses is frequently due to RNA recombination (130), a process that joins noncontiguous RNA segments together. Novel combinations of genes, motifs or regulartory RNA sequences resulting from recombination may cause dramatic changes in the infectious properties of RNA viruses. This, in turn helps viruses to escape natural resistance mechanisms and renders vaccines and other antibiral methods eneffective. Further, a recombinant virus may 'jump species", as has been propsed for the recombinat SARS coronavirus, a newly-emerged viral pathogen of humans (134, 136, 137). Despite the significance of RNA recombinatin in virus evolution, the roles of host genes in the recomginations process are currently unknown. This research will lead to better understanding of the effectof host genes on RNA recombination and therole of the host in virus evolution. Because the role of hoist genes in viral RNA recombination is currently unknown, the proposed work may dramatically change our view on the role of the host in viral RNA recombination. The development of tractable in vitro and in vivo model recomination systems based on Tombusviruses, will likely be beneficial to the studies on other, less amenable RNA viruses. This should help build more universal RNA recombination models. This promises longer lasting and more powerful antiviral methods. In addition, knowledge of RNA recombination will also be helpful in designing and using safer and more effective vaccines and viral-based gene-delivery vectors in humans, animals, and plants. Overall, studies on RNA recombination will likely advance major areas, including (1) host-virus interactions; (2) mechanism of RNA recombination; (3) nature and speed of RNA virus evolution; and (4) prediction of emergence of new viruses.