Cell cycle-regulated transcription by the human immunodeficiency virus type 1 Tat transactivator

Cyclin-dependent kinases are required for the Tat-dependent transition from abortive to productive elongation. Further, the human immunodeficiency vir us type 1 (HIV-1) Vpr protein prevents proliferation of infected cells by a rresting them in the G(2) phase of the cell cycle. These findings suggest t hat the life cycle of the virus may be integrally related to the cell cycle . We now demonstrate by in vitro transcription analysis that Tat-dependent transcription takes place in a cell cycle-dependent manner. Remarkably, Tat activates gene expression in two distinct stages of the cell cycle. Tat-de pendent long terminal repeat activation is observed in G(1). This activatio n is TAR dependent and requires a functional Sp1 binding site. A second pha se of transactivation by Tat is observed in G(2) and is TAR independent. Th is later phase of transcription is enhanced by a natural cell cycle blocker of HIV-1, vpr, which arrests infected cells at the G(2)/M boundary. These studies link the HIV-1 Tat protein to cell cycle-specific biological functi ons.