Effects on isolated human pancreatic islet cells after infection with strains of enterovirus isolated at clinical presentation of type 1 diabetes

Enterovirus (EV) infections have been associated with the pathogenesis of type I diabetes (TID). They may cause beta-cell destruction either by cytolytic infection of the cells or indirectly by triggering the autoimmune response. Evidence for EV involvement have been presented in several studies, EV-IgM antibodies have been reported in TID patients, EV-RNA has been found in the blood from TID patients at onset, and EV have been isolated from newly diagnosed TID. Our aim was to study infections with EV isolates from newly diagnosed TID patients in human pancreatic islets in vitro. Two of them (T1 and T2) originated from a mother and her son diagnosed with TID on the same day, the other two (A and E) were isolated from a pair of twins at the time of diagnosis of TID in one of them. Isolated human pancreatic islets were infected and viral replication, viability and degree of cytolysis as well as insulin release in response to high glucose were measured. All four EV isolates replicated in the islet cells and virus particles and virus-induced vesicles were seen in the cytoplasm of the P-cells. The isolates varied in their ability to induce cytolysis and to cause destruction of the islets and infection with two of the isolates (TI and A) caused more pronounced destruction of the islets. Infection with the isolate from the healthy twin boy (E) was the least cytolytic. The ability to secrete insulin in response to high glucose was reduced in all infected islets as early as 3 days post infection, before any difference in viability was observed. To conclude, strains of EV isolated from T I D patients at clinical presentation of TID revealed P-cell tropism, and clearly affected the function of the P-cell. In addition, the infection caused a clear increase in the number of dead cells. (c) 2006 Published by Elsevier B.V.