Host determinants of disease outcomes in arboviral infections

We will study bluetongue, one of the most important diseases found in livestock to address a fundamental question in infectious diseases: how can a pathogenic virus render some infected hosts seriously ill while causing only mild disease in others, despite abundant viral replication in both? Bluetongue disease is caused by bluetongue virus (BTV), a virus transmitted to animals by bites from midges. BTV can infect all domestic and wild ruminant species, but infection results in variable levels of disease. Sheep are more susceptible to bluetongue disease but goats and cows are more resilient and develop high levels of virus in their blood but rarely show signs of sickness.

We believe that these differences in clinical outcome are caused by events during the early stages of infection when the virus is attempting to replicate in a cell that is urgently mounting an antiviral immune response. We will experimentally test this idea and the results will advance our understanding of individual susceptibility to bluetongue disease, inform the design of appropriate control measures and serve as a model to study disease susceptibility in many other viral diseases that affect humans and animals.