Grant: Project Grant

Viruses are leading causes of illness and death, imposing major burdens on human health, the economy, and society at large. Despite impressive advances, most viral infections remain untreatable and new approaches to prevention and treatment are urgently required. Improved understanding of the basic details of how viruses function at the molecular level is essential to advance this agenda, and this knowledge will also provide additional health benefits. For example, a modified herpes simplex virus (HSV) was approved last year by the US FDA to treat malignant melanoma, the first oncolytic virus to be licensed for general use. My research seeks to determine how viruses reprogram the molecular machinery within our cells to produce more virus particles and evade our immune defenses. This Project focuses on an HSV protein that destroys the genetic instructions (DNA) located within mitochondria, the powerhouses of our cells. This protein also alerts our innate immune system, triggering antiviral defenses. We think that it does so through its assault on mitochondrial DNA. We will test this hypothesis, and learn how the effects on mitochondria affect virus replication. By determining how this newly discovered pathway works we will be able to exploit it to shore-up our immune defenses. This fundamental knowledge will allow us to devise new ways to inhibit virus replication, improve the effectiveness of herpesvirus vaccines, and improve the potency of oncolytic herpesviruses.