Translational effects of peptide antagonists of Tat protein of human immunodeficiency virus type 1

The Tat (trans-activator of transcription) regulatory protein of human immu nodeficiency virus (HIV-1) acts by interacting with the TAR RNA domain of n ascent viral transcripts and with cellular proteins to increase viral trans cription. In Jurkat-derived HCLE-D36 cells, which are stably transfected wi th the chloramphenicol acetyltransferase (CAT) reporter gene expressed from the TAR-encoding long terminal repeat (LTR) of HIV-1, CAT protein expressi on is dependent on Tat. The Tat9-K-biotin peptide antagonist of Tat binds s pecifically to TAR RNA and competes with Tat for binding. In the cellular e xpression system, Tat9-K-biotin reduces fat-dependent CAT expression, Howev er, while the Tat antagonist greatly reduces CAT protein production and pol ysome association of CAT mRNA, it has little effect on CAT mRNA levels, sug gesting that the antagonist works at the post-transcriptional level.