immunocompromised populations where the virus can cause systemic and even fatal infections. Indeed, we have shown that astrovirus infections are more prevalent than norovirus in our pediatric oncology population with many patients being long-term shedders. Due to the lack of cell culture systems and animal models for most astrovirus family members, little is known about pathogenesis. Our group demonstrated that the human astroviruses cause intestinal epithelial cells to lose cell-to-cell junctions resulting in increased membrane permeability (i.e. leaky gut). The virus does not have to replicate to induce membrane permeability. The outer viral coat protein, or capsid, is all that was required. To determine if this could also happen in vivo, animal models were orally inoculated with species-specific astrovirus or astrovirus capsid and intestinal permeability and clinical disease was monitored. Like cells in culture, the astrovirus capsid protein alone caused a loss of membrane permeability, relocalization of sodium transporters and diarrhea. Our initial work suggests the virus disrupts the barrier by causing the epithelial cells to change and undergo epithelial to mesenchymal transition.
1. Recognize the importance of astroviruses.
2. Illustrate how a viral toxin could cause diarrhea without causing damage to the intestinal cells.