Tat-independent Replication of Human Immunodeficiency Viruses

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1995 Jan 1

PMID 7814633

Citations 12

Authors

L Luznik

G Kraus

J Guatelli

D Richman

F Wong-Staal

Affiliations

Soon will be listed here.

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-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.

Citing Articles

In-depth single-cell analysis of translation-competent HIV-1 reservoirs identifies cellular sources of plasma viremia.

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Characterization of Inducible Transcription and Translation-Competent HIV-1 Using the RNAscope ISH Technology at a Single-Cell Resolution.

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The human antiviral factor TRIM11 is under the regulation of HIV-1 Vpr.

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An in-depth comparison of latent HIV-1 reactivation in multiple cell model systems and resting CD4+ T cells from aviremic patients.

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