mcelroy lab

We use primarily derived human samples to try to understand the pathophysiology of disease. The goal is to use this information to develop hypotheses about why some people get sick and others don’t. We focus our studies on various aspects of human physiology that are clearly clinically disrupted in patients with VHF; this includes aspects of endothelial function, coagulation pathways, inflammation and both innate and adaptive immune function. Only by understanding what is going right (or wrong) in the host can we begin to design therapeutics to augment or abrogate the effect.  

 While VHF’s can be quite deadly, they are (fortunately) not the most common viruses and special challenges accompany them- they require high biosafety levels and additional regulatory oversight. Since access to primary human samples can be difficult, an alternative is to model the disease in an animal. The added benefit of animal modeling is that hypotheses can be rigorously tested and therapeutic interventions can be evaluated. We have used the mouse model of RVFV to demonstrate that CD4 T cells are important for preventing viral encephalitis, which is a known complication of RVFV disease in humans.  

Sometimes the quickest way to understand why a virus is pathogenic is to study the virus in cells in the laboratory.  This principle certainly applies to RVFV. This virus encodes a protein (NSs) that is known to antagonize the interferon signaling system. Viruses that are missing this protein turn out to be completely non-pathogenic and have become the basis for several RVFV vaccines that are under development for use in livestock.  

The figure to the left shows NSs filaments in infected human hepatocytes.