COOPERATION BETWEEN HERPES-SIMPLEX VIRUS TYPE 1-ENCODED ICPO AND TAT TO SUPPORT TRANSCRIPTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 LONG TERMINAL REPEAT IN-VIVO CAN OCCUR IN THE ABSENCE OF THE TAR BINDING-SITE

Expression of human immunodeficiency virus type 1 (HIV-1) provirus can be stimulated by herpes simplex virus type 1 (HSV-1) infection; the s timulation occurs at the level of transcriptional activation of the HI V long terminal repeat (LTR) and is mediated by both cellular and HSV- 1-encoded transactivators. We have shown in this study that HSV-1 imme diate-early gene ICP0 cooperates effectively with the HN-l-encoded tra nsactivator, Tat, in the stimulation of HIV-1 LTR-directed transcripti on. The cooperation between ICP0 and Tat is specific for the HIV-I LTR and was not observed with other promoters (e.g., ICP0) that can be tr ansactivated by ICP0 but not by Tat. Analyses of HIV-1 LTR deletion mu tants have shown that ICP0 not only transactivates an HIV-1 LTR mutant that is unresponsive to NF-kappa B acid Tat-mediated transactivation, such as the HIV-1 LTR with the enhancer deleted (-83 LTR) and TAR del eted (+20 to +81), but also restores responsiveness to Tat. ICP0 also showed cooperation with Gal4-Tat fusion protein-mediated transactivati on of Gal4-HIV-1 LTR with TAR deleted. Enhancement of the transcriptio nal activation of ICP0 by Tat requires both the cysteine-rich acid cor e domains of Tat and is inhibited by RO5-3335. ICP0 stimulates transcr iption of not only the HIV-1 LTR but also the TAR-defective HIV-1 prov irus, We suggest that ICP0 can (i) recruit Tat to the vicinity of the HIV-1 promoter, thereby providing an alternative binding site for Tat, and (ii) substitute for the enhancer-binding proteins that are requir ed for efficient Tat transactivation in T cells.