The trans-activator gene of HTLV-III is essential for virus replication
Authors:
- Amanda G. FisherAFAmanda G. Fisher
- Mark B. FeinbergMFMark B. Feinberg
- Steven F. JosephsSJSteven F. Josephs
- Mary E. HarperMHMary E. Harper
- Lisa M. MarselleLMLisa M. Marselle
- Gregory ReyesGRGregory Reyes
- Matthew A. GondaMGMatthew A. Gonda
- Anna AldoviniAAAnna Aldovini
- Christine DeboukCDChristine Debouk
- Robert C. GalloRGRobert C. Gallo
- Flossie Wong-StaalFWFlossie Wong-Staal
- 1 March 1986
- journal article
- Published by Springer Nature in Nature
- Vol. 320 (6060) , 367-371
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). This gene, called tat-III, lies between the sor and env genes and is able to mediate activation, in a trans configuration, of the genes linked to HTLV-III long terminal repeat (LTR) sequences. We now present evidence that the product of tat-III is an absolute requirement for virus expression. We show that derivatives of a biologically competent molecular clone of HTLV-III, in which the tat-III 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 conditions, 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.Keywords
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