Rapid activation and subsequent down-regulation of the human immunodeficiency virus type 1 promoter in the presence of Tat: possible mechanisms contributing to latency.

The mechanism of induction of gene expression of the human immunodeficiency virus type 1 long terminal repeat (LTR) by the Tat transactivator protein was studied in a cell fusion assay. Tat causes a rapid activation of both transcription from the LTR and accumulation of hybrid LTR-chloramphenicol acetyltransferase mRNAs. Approximately 4 h after induction by Tat, expression from the LTR promoter is down-regulated, resulting in a decrease in the accumulation of LTR mRNA. This down-regulation of expression occurs in the continued presence of Tat. Protein synthesis inhibitors can block this down-regulation; therefore, the postinduction repression of expression is dependent upon de novo protein synthesis. We propose that a labile cellular protein(s) is responsible for the low levels of human immunodeficiency virus type 1 expression, possibly contributing to the establishment of a latent state of viral expression.