Many viruses must surmount the barrier presented by the epithelium lining the gastrointestinal and/or respiratory tracts to initiate infection. The intestines and airways are lined by polarized epithelial cells, which contain intercellular tight junctions (TJs) that provide a barrier to the migration of toxic materials (including viruses) from the lumen to the interstitium. Enteroviruses are transmitted via the fecal-oral route and therefore require passage through the intestinal mucosa to invade the host. Once infection begins within the intestine, the virus enters into the bloodstream and disseminates to other sites of infection. In order to access these sites, bloodborne virus would likely require passage through the polarized endothelium lining the vasculature (which also contains TJs to prevent pathogen access). For enteroviruses, sites of dissemination can include the central nervous system (CNS) and the heart. Because enteroviruses must pass from the bloodstream into the CNS, they may have to bypass or gain entry through the blood-brain barrier (BBB), a structure formed in part by the polarized endothelial cells lining the vessels surrounding the brain.

The mechanism(s) by which some enteroviruses (polioviruses and coxsackie B viruses) breach the barrier presented by the epithelium lining the intestinal tract and the endothelium composing the vasculature and BBB remains poorly understood and are the focus of projects in my lab. We utilize a variety of cell biological techniques in order to define the endocytic pathways used by virus to enter polarized monolayers and to define the intracellular signaling molecules that regulate these processes.