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Research Article Free access | 10.1172/JCI117660
Department of Medicine, University of California, School of Medicine, San Diego 92093.
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Department of Medicine, University of California, School of Medicine, San Diego 92093.
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Department of Medicine, University of California, School of Medicine, San Diego 92093.
Find articles by Guatelli, J. in: JCI | PubMed | Google Scholar
Department of Medicine, University of California, School of Medicine, San Diego 92093.
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Department of Medicine, University of California, School of Medicine, San Diego 92093.
Find articles by Wong-Staal, F. in: JCI | PubMed | Google Scholar
Published January 1, 1995 - More info
The replication of human immunodeficiency retroviruses involves a complex series of events that is regulated at both transcriptional and posttranscriptional levels. The tat gene product is a potent trans-activator of viral transcription and therefore an attractive target for the development of antiviral drugs. Tat-defective HIV-1 proviral DNA clones have been shown previously to be replication defective. In this study, we report that tat-defective HIV-1 and HIV-2 viral DNA transfected into U937 cells can direct efficient viral replication in the presence of transcriptional stimulators such as TNF-alpha and PMA. In MT-4 cells, tat-defective HIV-1 can replicate without any stimulation. The viruses recovered from MT-4 cells remained tat defective defined by their inability to infect T cell lines (e.g., Molt 4/8) although replication could be rescued with cytokines. Limited replication was observed in primary mononuclear cells. Furthermore, we showed that Ro 24-7429, a potent tat antagonist and antiviral compound, failed to suppress HIV-1 replication in TNF-alpha-stimulated T cells. These results have important implications for targeting tat as a therapeutic strategy for AIDS.
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