The work detailed in this manuscript focuses on the eukaryotic translation initiation factor 4E (eIF4E), a protein involved in recruiting host messenger RNA to the ribosomal complex. eIF4E is also an important host factor that is utilized by invading plant viruses in order to complete their lifecycle. A number of virus resistant alleles that have evolved independently in diverse crop species are now known to correspond to eIF4E. Current work has focused on transgenesis of resistance alleles to gain a better understanding of how specific amino acid changes contribute to virus resistance. We present three studies that continue this line of research and apply this knowledge to address an economically important pathosystem. The focus of the first chapter is on the evolutionary history of the eIF4E gene. We find that amino acids predicted to have been most strongly selected are those that are known to interact with a viral protein, suggesting that eIF4E resistance alleles have evolved in response to selective pressures exerted by phytopathogenic viruses. We then mutate the eIF4E gene from potato at specific amino acids in order to simulate natural evolutionary processes and disrupt eIF4E-viral interaction. When these mutated potato alleles are overexpressed in potato, they confer virus resistance. By using a potato gene to develop virus resistance, we hope to address the consumer and regulatory concerns that have thus far prevented commercialization of transgenic potato. Finally, we conduct a field experiment to study several resistant lines in more detail. We find that virus resistance is not associated with a decrease in any of the yield or quality characteristics measured. We suggest that the technique described here may be applied to potato and other crops in order to develop virus resistant varieties that are more acceptable to consumers than other methods of genetic engineering.