Virus infections in type 1 diabetes

Abstract

The precise etiology of type 1 diabetes (T1D) is still unknown, but viruses have long been suggested as a potential environmental trigger for the disease. However, despite decades of research, the body of evidence supporting a relationship between viral infections and initiation or acceleration of islet autoimmunity remains largely circumstantial. The most robust association with viruses and T1D involves enterovirus species, of which some strains have the ability to induce or accelerate disease in animal models. Several hypotheses have been formulated to mechanistically explain how viruses may affect islet autoimmunity and β-cell decay. The recent observation that certain viral infections, when encountered at the right time and infectious dose, can prevent autoimmune diabetes illustrates that potential relationships may be more complex than previously thought. Here, we provide a concise summary of data obtained in mouse models and humans, and identify future avenues toward a better characterization of the association between viruses and T1D.

Figure 1.

Antiviral, diabetogenic CTL in the RIP-LCMV.GP diabetes model as visualized by intravital two-photon imaging in the pancreas. The technique is described in Coppieters et al. (2010). Briefly, purified and labeled P14 TCR-transgenic CTL is transferred to RIP-LCMV.GP hosts, followed by infection with LCMV. As such, the kinetics of the diabetogenic CTL response can be dynamically visualized in the pancreas. (Magenta) Insulin-producing β cells, (green) CTL, (red) vasculature after dye injection.

Figure 2.

Potential immune mechanisms leading to islet inflammation or tolerance following viral infection.

Figure 3.

Aberrant MHC class I hyperexpression in islets from a 12-yr-old boy with one year of T1D duration (nPOD case 6052). Frozen pancreas section was stained for immunofluorescence and analyzed by confocal microscopy. Note the abundance of CD8⁺ cellular infiltration. (For details see Gianani et al. 2010.)