The full-length Tat protein is required for TAR-independent, posttranscriptional trans activation of human immunodeficiency virus type 1 env gene expression.

Tat is a protein that dramatically increases the expression of all genes expressed from the human immunodeficiency virus type 1 (HIV-1) long terminal repeat through interaction with a cis-acting target sequence referred to as TAR (for trans-acting responsive region). The tat gene is divided into two coding exons which, when translated, result in the synthesis of an 86-amino-acid protein. However, the 72-amino-acid segment encoded by the first coding exon of tat is sufficient to encode a fully active Tat protein in known assays. We examined expression of the env gene from an LTR that lacks TAR (designated dTAR-env). Surprisingly, only the full-length Tat peptide trans activated expression of the env gene from dTAR-env. Comparison of RNA and protein expression of the env gene in the presence of Tat indicated that the mechanism of trans activation is posttranscriptional rather than transcriptional. To test whether the TAR-independent Tat function is specific to the HIV-1 env gene, we analyzed expression of heterologous genes from the long terminal repeat lacking TAR. These heterologous genes were not trans activated by Tat in the absence of a TAR element, which suggests that the second-exon peptide of Tat has a sequence-specific role in TAR-independent trans activation of the HIV-1 env gene. Analysis of a mutant in the 5' end of the env gene was used to identify a cis-acting sequence required for Tat responsiveness.