Initiation of Human Immunodeficiency Virus Type 1 (HIV-1) Transcription is Inhibited by Noncytolytic CD8+ Suppression



R Glenn Overman1, §, Anthony L Llorens3, §, Michael L Greenberg6, Mariano A Garcia-Blanco3, 4, Georgia D Tomaras*, 1, 2, 4
1 Department of Surgery, Duke University Medical Center, Durham, NC, USA
2 Department of Immunology, Duke University Medical Center, Durham, NC, USA
3 Department of Medicine, Duke University Medical Center, Durham, NC, USA
4 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA
6 Trimeris, Inc., Morrisville, NC, USA


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2007 Bentham Science Publishers Ltd.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the Departments of Surgery, and Molecular Genetics and Microbiology, Rm. 205 SORF, LaSalle Street Ext., P.O. Box 2926, Duke University Medical Center, Durham, NC 27710, USA; Tel: (919) 681-5598; Fax: (919) 684-4288; E-mail: gdt@duke.edu
§ These authors contributed equally to this work.


Abstract

The replication of human immunodeficiency virus type 1 (HIV-1) can be inhibited by noncytolytic CD8+ T cell mediated suppression, an immune response that specifically targets HIV-1 gene expression. Clinical studies demonstrate that this immune response may play an important role in the host defense against HIV infection. In this study, we examined the distinct steps in viral gene expression for inhibition by noncytolytic CD8+ T cells. A primary HIV-1 infection system of CD4+ enriched peripheral blood mononuclear cells was utilized to examine the HIV-1 life cycle as a relevant ex vivo system. Established CD8+ T cell lines from two HIV+ long-term nonprogressors were used to examine differences at the level of transcriptional initiation and elongation of the HIV genome. This infection system coupled with the results from real-time measurement of newly transcribed RNA transcripts determined that there was a significant decrease (5-8 fold) in short intracellular viral RNA transcripts. These data strongly favor a role for the initiation of virus transcription in noncytolytic CD8+ T cell mediated suppression.