Federal Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded the University of Pittsburgh $201,608 under the Allergy and Infectious Diseases Research program (CFDA 93.855) through a Project Grant effective June 12, 2026, with a completion date of May 31, 2028. This research project delivers scientific investigation into the mechanisms by which enteric viruses induce loss of oral tolerance and trigger autoimmune responses, specifically focusing on how the Type 1 Lang (T1L) strain of reovirus initiates inflammatory pathways that may lead to celiac disease. The research outputs will include detailed characterization of the ZBP1 (Z-DNA-binding protein 1) pathway, documentation of how viral Z-RNA (a specific form of ribonucleic acid) triggers necroptosis in intestinal epithelial cells, and analysis of how this cellular death process alters dendritic cell function to promote inflammatory immune responses against dietary antigens.

The project is structured in two primary aims that together will generate mechanistic insights and potentially identify intervention points for disease prevention or treatment. Aim 1 deliverables will focus on characterizing the molecular detection of viral Z-RNA and its role in inducing necroptosis in intestinal epithelial cells. Aim 2 will produce experimental evidence demonstrating the causal relationship between necroptosis and loss of oral tolerance, along with testing whether blocking or engaging the ZBP1-mediated pathway can prevent or induce gluten-specific T-helper 1 immune responses. These research outputs are intended to advance understanding of viral contributions to autoimmune and food-related diseases and may inform future therapeutic strategies for celiac disease prevention and treatment.