ACTIVATION OF THE INTERFERON-INDUCIBLE ENZYMES, 2',5'-OLIGOADENYIATE 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-1) Rex r esponse element (Rex-RE) activates the interferon-induced 2', 5'-oligo adenylate synthetase (2-5OAS) in a dose-dependent manner. In addition, Rex-RE at 1 mu g/ml activates a second interferon-induced enzyme, p68 kinase (PKR); however, at 50 mu g/ml, Rex-RE inhibits PKR activity. P oly(rl)-poly(rC) (10 mu g/ml) dissociates the ribonucleoprotein comple xes, Rex-RE/2-5OAS, or Rex-RE/PKR, whereas poly(rC) (100 mu g/ml) does not, indicating the presence of high affinity interactions between Re x-RE and these two enzymes. To further characterize the interaction of Rex-RE with 2-5OAS and PKR, [P-32]Rex-RE was uv-cross-linked to 2-5OA S and PKR present in interferon-treated HeLa cell extracts. The affini ty of Rex-RE to highly purified 40-kDa human recombinant 2-5OAS was de termined to be K-d = 4.7 nM. The relevance of these results to the pat hogenesis of HTLV-I-associated adult T-cell leukemia/lymphoma is discu ssed. (C) 1995 Academic Press, Inc.