Localization of enteroviral RNA within the pancreas in donors with T1D and T1D-associated autoantibodies

Enteroviral infections have been associated with autoimmunity and type 1 diabetes (T1D), but reliable methods to ascertain localization of single infected cells in the pancreas were missing. Using a single-molecule-based fluorescent in situ hybridization (smFISH) method, we detected increased virus infection in pancreases from organ donors with T1D and with disease-associated autoantibodies (AAb(+)). Although virus-positive β cells are found at higher frequency in T1D pancreases, compared to control donors, but are scarce, most virus-positive cells are scattered in the exocrine pancreas. Augmented CD45(+) lymphocytes in T1D pancreases show virus positivity or localization in close proximity to virus-positive cells. Many more infected cells were also found in spleens from T1D donors. The overall increased proportion of virus-positive cells in the pancreas of AAb(+) and T1D organ donors suggests that enteroviruses are associated with immune cell infiltration, autoimmunity, and β cell destruction in both preclinical and diagnosed T1D.