Prospective virome analyses in young children at increased genetic risk for type 1 diabetes

Viruses are implicated in the autoimmune destruction of the pancreatic islet β-cells that results in insulin deficiency and type 1 diabetes (T1D)(1–4). Certain enteroviruses can infect β-cells in vitro(5), have been detected in pancreatic islets of T1D patients(6) and shown an association with T1D in meta-analyses(4). However, establishing consistency of findings across studies has proved difficult. Obstacles to convincingly link RNA viruses to islet autoimmunity may be attributed to rapid viral mutation rates, cyclical periodicity of viruses(7) and the selection of variants with altered pathogenicity and ability to spread in populations. β-cells strongly express cell surface Coxsackie and adenovirus receptor (CXADR) genes, which can facilitate enterovirus infection(8). Studies of human pancreata and cultured islets have shown significant variation in enteroviral virulence to β-cells between serotypes and within the same serotype(9–10). In this large-scale study of known eukaryotic DNA and RNA viruses in stools from children, we evaluated fecally shed viruses in relation to islet autoimmunity and T1D. This study demonstrated prolonged Enterovirus B (EV-B) rather than independent, short duration EV-B infections may be involved in the development of islet autoimmunity, but not T1D, in some young children. Furthermore, we found fewer early life Human mastadenovirus C infections and CXADR rs6517774 independently correlated with islet autoimmunity.