Transcriptional but not translational regulation of HIV-1 by the tat gene product

Abstract

Human immunodeficiency virus-1 (HIV-1), which causes AIDS (acquired immune deficiency syndrome), possesses an essential gene, tat, whose product, acting through the long terminal repeat (LTR) sequences of HIV-1, activates viral genes and replication. The mechanism by which tat trans-activates HIV genes is unclear. Some studies have reported that an increase in messenger RNA accumulation directed by the HIV-1 LTR can explain the action of tat, but others suggest that this increase in mRNA levels can only partially explain trans-activation, and that translational control mechanisms may also be involved. To test those possibilities we have established an efficient adenovirus system for delivering the HIV-1 LTR attached to a reporter gene (chloramphenicol acetyltransferase; CAT) into cells and monitoring its activity. The HIV-1 LTR expressed from this adenovirus responds to trans-activation in a HeLa cell line constitutively expressing the tat protein by increasing the transcription rate of the HIV-1 LTR and the accumulation of mRNA encoding CAT. In this system the translational efficiency of this CAT mRNA in the cell is unaffected by the presence of tat.