Tat-independent replication of human immunodeficiency viruses

Leo Luznik, Günter Kraus, John Guatelli, Douglas Richman, Flossie Wong-Staal

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)328-332
Number of pages5
JournalJournal of Clinical Investigation
Volume95
Issue number1
DOIs
StatePublished - Jan 1995
Externally publishedYes

Keywords

  • Ro 24-7429
  • TNF-α
  • cytokines
  • human immunodeficiency virus
  • tat

ASJC Scopus subject areas

  • Medicine(all)

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