The trans-activator gene of HTLV-III is essential for virus replication.

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 6th open reading frame in addition to the 5 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. Evidence is now presented that the product of tat-III is an absolute requirement for virus expression. The authors 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 repectively 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. (authors modified)