The viral paradigm in type 1 diabetes: Who are the main suspects?

Type 1 diabetes (T1D) is an autoimmune disease characterized by the loss of pancreatic beta cells in the islets of Langerhans. Although genetic predisposition plays an important role in T1D development, studies of identical twins suggest that environmental factors such as viruses and other pathogens may be critical triggers either through direct cytolytic effect and gradual beta cell destruction, or by bystander activation of the immune system. In addition, viruses may circumvent the host immune response and have the capacity to establish chronic lifelong infections. The association of various viral infections with the induction of T1D has been extensively studied at the serological and epidemiological level. However, there is still little evidence from studies of human pancreas to confirm their presence or a causal role in disease pathogenesis. In this review, we identify possible suspects for viral triggers of disease and explain their potential roles in the "viral paradigm" of T1D.