Murine Pancreatic Beta TC3 Cells Show Greater 2^′,5^′-Oligoadenylate Synthetase (2^′5^′AS) Antiviral Enzyme Activity and Apoptosis Following IFN-𝛼 or Poly(I:C) Treatment than Pancreatic Alpha TC3 Cells

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.