Evolutionary change driven by historical viral epidemics has left a molecular “fossil record” in our DNA sequence. Our goal is to learn about natural strategies that have been successful at beating viruses in the past, and how these might be exploited in the fight against modern viral attacks. We are using a broad array of techniques from molecular evolution, virology, experimental evolution, and comparative genomics to look at human and primate genes that encode inhibitors of viral infection. We are also interested in a systems biology approach to explore how human genes change enough to avoid susceptibility to new viruses, yet still maintain their ability to perform other important cellular functions. We are interested in the inverse effects that evolutionary change can have on multiple, intertwined biological systems.