Abstract
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-α 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-α-stimulated T cells. These results have important implications for targeting tat as a therapeutic strategy for AIDS.
Original language | English (US) |
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Pages (from-to) | 328-332 |
Number of pages | 5 |
Journal | Journal of Clinical Investigation |
Volume | 95 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1995 |
Externally published | Yes |
Keywords
- Ro 24-7429
- TNF-α
- cytokines
- human immunodeficiency virus
- tat
ASJC Scopus subject areas
- General Medicine