Figure 9.

Schematic presentation of a model of induction of beta cell apoptosis during viral infections. Virus infections result in production of IFN-α and dsRNA. IFN-α induces expression of 2′5′AS though the classical IFN-α signal transduction pathway, and dsRNA can lead to induction of IFN-α/β and to expression of 2′5′AS via TLR3-mediated signaling pathway. In the presence of dsRNA, 2′5′AS is activated. The 2′5′A oligomers generated by 2′5′AS stimulate RNaseL-induced apoptosis, which results in subsequent beta cell autoimmunity. 2′5′AS can also promote cellular apoptosis via an enzyme activity-independent pathway. In genetically predisposed individuals, increased insulin gene expression may produce dsRNA-like molecules that contribute to enhancement of the activation and induction of 2′5′AS in beta cells.