Suppression of HIV type 1 replication by a dominant-negative Ets-1 mutant

Activity of the distal region of the human immunodeficiency virus (HIV-1) l ong terminal repeat (LTR), which contains binding sites for the Ets-1 and U SF-1 proteins, is integral for HIV-1 replication. The Ets-1 and USF-1 prote ins play a critical role in the activity of the HIV-1 LTR distal enhancer r egion, as indicated by the potent dominant negative effect of a mutant Ets- 1 lacking trans-activation domains on the transcriptional activity of the L TR. To determine the biological relevance of the Ets-1 and USF-1 proteins i n HIV-1 replication, we examined the effect of expression of the dominant-n egative mutant of Ets-1 (dnEts-1) on HIV-1 infection of T cells. We demonst rated that expression of dnEts markedly suppressed HIV-1 infection of a T c ell line. This finding indicates that formation of a transcriptionaly activ e USF-1/Ets-1 complex is important in the productive infection of cells by HIV-1, and suggests that inhibition of the interaction between USF-1 and Et s-1 with the HIV-1 LTR may provide a new target for anti-HIV-1 gene therapy .