Abstract
Studies of the genomic structure of human T-lymphotropic virus type III (HTLV-III) and related viruses, implicated as the causal agent of acquired immune deficiency syndrome (AIDS), have identified a sixth open reading frame in addition to the five previously known within the genome (gag, pol, sor, env and 3′orf)1–4. This gene, called tat-III, lies between the sorand env genes and is able to mediate activation, in a trans configuration, of the genes linked to HTLV-III long terminal repeat (LTR) sequences5–8. We now present evidence that the product of far-III is an absolute requirement for virus expression. We show that derivatives of a biologically competent molecular clone of HTLV-III9, in which the tat-Ill gene is deleted or the normal splicing abrogated, failed to produce or expressed unusually low levels of virus, respectively, when transfected into T-cell cultures. The capacity of these tat-III-defective genomes was transiently restored by co-transfection of a plasmid clone containing a functional tat-III gene or by introducing the tat-III protein itself. As HTLV-III and related viruses are the presumed causal agents of AIDS and associated conditions10–12, the observation that tat-III is critical for HTLV-III replication has important clinical implications, and suggests that specific inhibition of the activity of tat-III could be a novel and effective therapeutic approach to the treatment of AIDS.
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Fisher, A., Feinberg, M., Josephs, S. et al. The trans-activator gene of HTLV-III is essential for virus replication. Nature 320, 367–371 (1986). https://doi.org/10.1038/320367a0
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DOI: https://doi.org/10.1038/320367a0
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