- a o t v r C 1 p The human immunodeficiency virus type 1 (HIV-1) enodes a transcriptional transactivator called Tat (hTat) Cullen, 1998; Emerman and Malim, 1998; Frankel and oung, 1998; Gait and Karn, 1995; Gaynor, 1995; Jeang, 998; Jones, 1997; Jones and Peterlin, 1994). hTat is xpressed early in the life cycle of HIV-1 and is essential or viral gene expression, replication, and pathogenesis Dayton et al., 1986; Fisher et al., 1986). Unlike other nown eukaryotic transcriptional activators that bind to NA, hTat interacts with the transactivation response TAR; hTAR) RNA structure, which is located at the 59 end f all viral transcripts. Moreover, hTat regulates the proess of elongation rather than initiation of transcription Jones and Peterlin, 1994; Kao et al., 1987). In its absence, ranscription complexes assemble on the viral promoter LTR), but RNA polymerase II (RNAPII) synthesizes only hort transcripts (Kao et al., 1987). The binding of hTat to TAR renders the RNAPII competent for elongation (Kao t al., 1987; Laspia et al., 1989; Feinberg et al., 1991). This igh affinity interaction between hTat and hTAR is medited by the cyclin subunit of the positive elongation actor b (P-TEFb). By interacting with the human cyclin T1 hT1), hTat recruits the cyclin-dependent kinase 9 CDK9), which phosphorylates the C-terminal domain CTD) of RNAPII. The conversion of RNAPII from its nphosphorylated (RNAPIIa) to phosphorylated (RNAIIo) forms marks the transition from initiation to elongaion of transcription (Jones, 1997). This review begins with structures of hTat and hTAR. ext, we present genetic and biochemical evidence that ed to the current model of hTat transactivation. After a iscussion of other lentiviral Tat proteins, which recruit -TEFb by slightly different mechanisms, Tat transactivaion is placed into the context of eukaryotic transcription.