The long-term objective of this project is to understand the virus-host interactions that govern whether a host is susceptible or resistant to a virus. For positive-strand RNA viruses, these interactions affect virus entry, genome expression, genome replication, assembly, intercellular movement, and pathogenicity. Many of the intracellular virus-host interactions involving these viruses are highly conserved between animals, plants and eukaryotic microbes. In addition, virus-host interactions can have profound effects on host development. To identify functionally important host compatibility or defense factors, Arabidopsis thaliana is used to identify mutants with altered susceptibility to picornavirus-like plant potyviruses. The mutants provide the resource to identify factors and cellular processes that affect different stages of the infection cycle, including those that are targeted by viral counterdefensive mechanisms. The experimental plan takes advantage of the unique attributes of Arabidopsis as a genetically and genomically tractable model host to address the functions of two cellular compatibility factors that were identified in screens for potyvirus susceptibility mutants. The plan also exploits Arabidopsis and Nicotiana benthamiana to explore virus-host interactions involved in virus-mediated suppression of RNA silencing defense and RNA-controlled developmental pathways during infection. The project has two major Specific Aims : . Understand the functions of two host compatibility factors - elF(iso)4E and LSP2 - in infected and non-infected cells. These proteins are required for systemic infection by potyviruses. The interactions of these proteins with viral and cellular factors, and the roles of these proteins in infected and noninfected cells, will be determined. . Understand how virus-encoded RNA silencing suppressors work to inhibit silencing and microRNA-based developmental pathways during virus infection. Interactions between several viral silencing suppressors and cellular complexes and regulatory RNAs, and the interactions between suppressors and microRNA-controlled developmental pathways, will be examined.