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) long terminal repeat (LTR), which contains binding sites for the Ets-1 and USF-1 proteins, is integral for HIV-1 replication. The Ets-1 and USF-1 proteins play a critical role in the activity of the HIV-1 LTR distal enhancer region, as indicated by the potent dominant negative effect of a mutant Ets-1 lacking trans-activation domains on the transcriptional activity of the LTR. To determine the biological relevance of the Ets-1 and USF-1 proteins in HIV-1 replication, we examined the effect of expression of the dominant-negative mutant of Ets-1 (dnEts-1) on HIV-1 infection of T cells. We demonstrated that expression of dnEts markedly suppressed HIV-1 infection of a T cell line. This finding indicates that formation of a transcriptionaly active 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 Ets-1 with the HIV-1 LTR may provide a new target for anti-HIV-1 gene therapy.
Posada
R
R
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Pettoello-Mantovani
M
M
Sieweke
M
M
Graf
T
T
Goldstein
H
H
D002455:Cell Division; D002460:Cell Line; D004268:DNA-Binding Proteins; D005822:Genetic Vectors; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D009154:Mutation; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014161:Transduction, Genetic; D014162:Transfection; D051720:Upstream Stimulatory Factors; D014779:Virus Replication
D004268:DNA-Binding Proteins; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors