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Transcriptional Profiles of Latent Human Immunodeficiency Virus in Infected Individuals: Effects of Tat on the Host and Reservoir

Departments of Medicine, Microbiology, and Immunology,¹ Positive Health Program, San Francisco General Hospital, Center for AIDS Research,² Department of Pathology, University of California, San Francisco,⁴ Center for Biomedical Laboratory Sciences, San Francisco State University, San Francisco, California³

Received 9 January 2003/ Accepted 24 April 2003

The persistence of human immunodeficiency virus (HIV) in optimally treated infected individuals poses a major therapeutic problem. In latently infected cells, one of the observed phenotypes is absent elongation of viral transcription. Thus, the positive elongation factor b (P-TEFb), which is usually recruited by NF-B or Tat, is not present on the HIV long terminal repeat (LTR). Although most attempts to activate these proviruses centered on NF-B, we investigated effects of Tat. To this end, we generated transgenic mice, which secreted a chimera between Tat and the green fluorescent protein from ß cells of the pancreas. This extracellular Tat distributed widely, entered nuclei of resting cells, and specifically transactivated the HIV LTR. No deleterious side effects of Tat were found. Next, we determined that Tat can activate latent proviruses in optimally treated infected individuals. In their cells, T-cell activation or exogenous Tat could induce viral replication equivalently. Thus, P-TEFb could activate the majority of the latent HIV, in this case by Tat.

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