Increased IFN-alpha-induced sensitivity but reduced reactivity of 2',5'-oligoadenylate synthetase (2,5AS) in trisomy 21 blood lymphocytes

Abstract

2,5AS is induced by interferon-alpha, -beta (IFN-alpha, -beta) and polymerizes adenosine triphosphate (ATP) into pppA (2'p5'A) oligomers, leading to inhibition of protein synthesis and virus growth. The gene coding for the IFN-alpha, -beta receptor is localized to chromosome 21. In trisomy 21 cells from patients with Down's syndrome a 50% increase in gene dosage is present for the genes on this chromosome. Corresponding increase of gene products has been shown for several of these genes, e.g. the IFN-alpha, -beta receptor molecules. Here, we show a direct proportionality between the number of IFN-alpha, -beta receptors and both the basal activity of 2,5AS and the sensitivity of this enzyme for IFN-alpha, -beta. The relative increase of 2,5AS activity (the reactivity) becomes reduced consistent with the increased basal 2,5AS activity in trisomy 21 cells compared with control cells.