If type 1 diabetes (T1D) is caused/triggered by a viral infection in select genetic backgrounds – and Enteroviruses (EVs) are felt as major culprits – investigators are expecting to find EVs into pancreatic Langerhans islets and also in association with spleen, lymph nodes, peripheral blood leukocytes. Infection of lymphoid cells, in fact, is common in systemic infections. Using an original method that couples virus amplification in susceptible cells with RNA amplification assays capable of detecting persistent and mutated EV types, we showed that different EV species are present in blood leukocytes of two thirds of children/adolescents at the clinical onset of T1D. Initial study of living cells from nPOD cases (T1D, non-diabetics) demonstrated that EV genomes and infectivity are present also in spleen and lymph nodes of T1D cases (1 to 30 years post-diagnosis). Thus, EVs appear to produce chronic silent infections in diabetes as in the post-polio syndrome (that is being studied by our group). If the viral genome is present, then virus proteins should also be detectable. Initial work done with colleagues looking at the same nPOD samples by ISH, immunohistochemistry, proteomics showed a strong concordance between genome detection and protein expression. So far, we have been successful in sequencing short stretches of RNA encoding conserved EV enzymes. We failed, however, in detecting genes encoding EV capsid proteins. This may be due to the pronounced variability of these proteins, especially in chronic infections. An additional aim of our studies is to determine which leukocyte subsets are carrying EVs. Preliminary results suggest that T cell subsets may be infected. Evidence in this direction, would push the idea that virus-induced immune disturbances might contribute to autoimmunity in T1D. Proof that chronic EV infections are indeed associated with T1D has not been reached, however collaborative studies of the same nPOD cases using many different approaches will certainly reveal if the virus hypothesis is a viable one. Should EVs be implied, major implications for human health will ensue (antivirals, novel preventive measures, etc.).