Publications by authors named "V Bonnevie-Nielsen"

Double-stranded RNA (dsRNA) can induce antiviral enzyme 2',5'-oligoadenylate synthetase (2'5'AS) expression and activate latent 2'5'AS. Our previous data have shown pancreatic β cells are sensitive to dsRNA-induced 2'5'AS expression, and constitutive high basal 2'5'AS expression is associated with susceptibility to developing type 1 diabetes (T1D), a disease due to pancreatic β cell loss. Here we report that in vitro transcribed human insulin mRNA induces the activation of human OAS gene promoter sequences, and specifically and dose-dependently induces 2'5'AS expression in murine pancreatic βTC3 cells.

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Type 1 diabetes is caused by autoimmune destruction of pancreatic beta cells, possibly virus initiated. Virus infection induces alpha-interferon (IFN-alpha), leading to upregulation of genes encoding double-stranded (ds) RNA-dependent antiviral enzymes 2', 5'-oligoadenylate synthetase (2'5'AS) and PKR (p68). To investigate whether beta cell specificity could be due to antiviral differences between beta and alpha cells, we treated beta and alpha TC3 cell lines with IFN-alpha and/or poly(I:C) (a synthetic dsRNA).

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Both genetic and nongenetic factors contribute to the development of type 1 diabetes. Many investigations, including prospective studies of high-risk children, have implicated virus infections as predisposing environmental agents. We previously reported that basal activity of the key antiviral enzyme 2'5'-oligoadenylate synthetase (2'5'AS) was significantly elevated in type 1 diabetic patients compared with healthy control subjects.

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It is likely that human genetic differences mediate susceptibility to viral infection and virus-triggered disorders. OAS genes encoding the antiviral enzyme 2',5'-oligoadenylate synthetase (2'5'AS) are critical components of the innate immune response to viruses. This enzyme uses adenosine triphosphate in 2'-specific nucleotidyl transfer reactions to synthesize 2',5'-oligoadenylates, which activate latent ribonuclease, resulting in degradation of viral RNA and inhibition of virus replication.

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Bone remodelling changes within the menstrual cycle. Though the luteal phase is accompanied by decreased bone resorption, it is also paradoxically a time of increased production of bone resorptive cytokines. The present study examined the hypothesis that changes in serum osteoprotegerin (OPG) within the menstrual cycle prevent the increase in bone remodelling, which would otherwise have been the result of the luteal increase in the capacity for producing resorptive cytokines.

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