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

Abstract

SUMMARY 2,5 AS is induced by interferon-alpha, -beta (IFN-α, -β) 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-α, -β receptor is localized lo 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-α, -β receptor molecules. Here, we show a direct proportionality between the number of IFN-α, -β receptors and both the basal activity of 2,5AS and the sensitivity of this enzyme for IFN-α, -β. 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.