THE ABILITY OF POSITIVE TRANSCRIPTION ELONGATION-FACTOR-B TO TRANSACTIVATE HUMAN-IMMUNODEFICIENCY-VIRUS TRANSCRIPTION DEPENDS ON A FUNCTIONAL KINASE DOMAIN, CYCLIN T1, AND TAT

By binding to the transactivation response element (TAR) RNA, the tran scriptional transactivator (Tat) from the human immunodeficiency virus increases rates of elongation rather than initiation of viral transcr iption. Two cyclin dependent serine/threonine kinases, CDK7 and CDK9, which phosphorylate the C-terminal domain of RNA polymerase II, have b een implicated in Tat transactivation in vivo and in vitro. In this re port, we demonstrate that CDK9, which is the kinase component of the p ositive transcription elongation factor b (P-TEFb) complex, can activa te viral transcription when tethered to the heterologous Rev response element RNA via the regulator of expression of virion proteins (Rev). The kinase activity of CDK9 and cyclin T1 is essential for these effec ts. Moreover, P-TEFb binds to TAR only in the presence of Tat. We conc lude that Tat-P-TEFb complexes bind to TAR, where CDK9 modifies RNA po lymerase II for the efficient copying of the viral genome.