Viruses emerging from zoonotic reservoirs represent a major threat to public health. Understanding how host proteins engage with viruses across diverse virus and host species is important for understanding how viruses cross species barriers to cause disease in a new host. The innate immune system is a critical line of defense against zoonotic pathogens. Innate immune-associated genes are amongst the most diverse within and between species, yet much of what we know about activation and regulation of immune programs stems from studies in humans and mice. Our research uses combined evolutionary, biochemical, immunology, and virology approaches to characterize how virus and host species diversity affects activation or inhibition of innate immune pathways, particularly those involved in cell death and inflammation. This approach can also be applied to additional immune pathways to provide important insight into the mechanisms of immune activation and virus antagonism across vertebrates.
