Evolutionary Warfare: Characterizing Viral Antagonism of Host Innate Immune Components
Host-pathogen conflicts are major drivers of evolution and generate a seemingly endless array of challenges to the fields of medicine and scientific research. While extensive work has been conducted to combat diseases caused by viruses and to understand their molecular mechanisms, there is a need for better tools to identify and predict host components that have interacted with viruses over evolutionary history. By seeking out these evolutionary battlegrounds, we can discover novel and otherwise difficult-to-identify struggles between viruses and their hosts. Many logical host targets, such as sensors of non-self markers and effectors of the immune system have been characterized as important players in host defense. Here, I describe two instances of the evolution-guided discovery of unique viral interactors of the host innate immune response. The first chapter characterizes a host-evolved “tripwire” immune sensor that baits viruses into activation, and the second chapter details virus-driven evolution of a previously undescribed effector of the host innate immune response.