Mutational analysis of the human T-cell leukemia virus type I trans-acting rex gene product

Expression of the human T-cell leukemia virus type I (HTLV-I) rex gene is a prerequisite for the expression of the retroviral structural proteins. We have generated internal deletion mutants of this 27-kDa nucleolar trans-acting gene product to define functional domains in the Rex protein. The phenotype of the various mutant proteins was tested on the homologous HTLV-I rex response element sequence and the heterologous human immunodeficiency virus type 1 (HIV-1) rev response element sequence. Our results indicate that a region between amino acid residues 55 and 132 in the 189-amino-acid Rex protein is required for Rex-mediated trans activation on both retroviral response element sequences. In addition, substitution of the Rex nuclear localization signal by a sequence of the HIV-1 rev gene product targets the Rex protein to the correct subcellular compartment required for Rex function. Replication of human T-cell leukemia virus type I (HTLV-I), the causative agent of adult T-cell leukemia (16, 30, 31, 38), is dependent on the function of the virus-encoded trans-acting regulatory protein Rex. The Rex protein recog-nizes the viral mRNAs via a cis-acting sequence, named the rex response element (RxRE), located in the 3 ' long terminal repeat (LTR) of HTLV-I (15, 17, 18, 34). Rex function results in the cytoplasmic accumulation of unspliced (gag! pol) or singly spliced (env) viral mRNAs which serve either as the viral genome or as the template for translation into th