Activation of the interferon-inducible enzymes, 2',5'-oligoadenylate synthetase and PKR by human T-cell leukemia virus type I Rex-response element.

In vitro-synthesized human T-cell leukemia virus type 1 (HTLV-I) Rex response element (Rex-RE) activates the interferon-induced 2',5'-oligoadenylate synthetase (2-50AS) in a dose-dependent manner. In addition, Rex-RE at 1 microgram/ml activates a second interferon-induced enzyme, p68 kinase (PKR); however, at 50 micrograms/ml, Rex-RE inhibits PKR activity. Poly(rl)-poly(rC) (10 micrograms/ml) dissociates the ribonucleoprotein complexes, Rex-RE/2-5OAS, or Rex-RE/PKR, whereas poly(rC) (100 micrograms/ml) does not, indicating the presence of high affinity interactions between Rex-RE and these two enzymes. To further characterize the interaction of Rex-RE with 2-5OAS and PKR, [32P]Rex-RE was uv-cross-linked to 2-5OAS and PKR present in interferon-treated HeLa cell extracts. The affinity of Rex-RE to highly purified 40-kDa human recombinant 2-5OAS was determined to be Kd = 4.7 nM. The relevance of these results to the pathogenesis of HTLV-I-associated adult T-cell leukemia/lymphoma is discussed.