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Analysis of HIV-1 Viremia and Provirus in Resting CD4+ T Cells Reveals a Novel Source of Residual Viremia in Patients on Antiretroviral Therapy
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J. Virol. doi:10.1128/JVI.02568-08
JVI Accepts, published online ahead of print on 17 June 2009
Timothy P. Brennan1, John O. Woods2, Ahmad R. Sedaghat3, Janet D. Siliciano3, Robert F.
Siliciano3,4, and Claus O. Wilke2, 5*
8 1. Department of Molecular Biology and Genetics, The Johns Hopkins University
School of Medicine, Baltimore, MD 21205
2. Institute for Cell and Molecular Biology, The University of Texas at Austin, Austin,
TX 78712
3. Department of Medicine, The Johns Hopkins University School of Medicine,
Baltimore, MD 21205
4. Howard Hughes Medical Institute, Baltimore, MD 21205
5. Center for Computational Biology and Bioinformatics and Section of Integrative
Biology, The University of Texas at Austin, Austin, TX 78712
Abstract: Highly active antiretroviral therapy (HAART) can reduce HIV-1 viremia to clinically undetectable levels. Despite this dramatic reduction, some virus is present in the blood. Additionally, a long-lived latent reservoir for HIV-1 exists in resting memory CD4+ T cells. This reservoir is believed to be a source of the residual viremia and is the focus of eradication efforts. Here, we employ two measures of population structure, analysis of molecular variance and the Slatkin-Maddison test, to demonstrate that the residual viremia is genetically distinct from proviruses in resting CD4+ T cells, but that proviruses in resting and activated CD4+ T cells belong to a single population. Residual viremia is genetically distinct from proviruses in activated CD4+ T cells, monocytes, and unfractionated peripheral blood mononuclear cells. The finding that some of the residual viremia in patients on HAART stems from an unidentified cellular source other than CD4+ T cells has implications for eradication efforts.
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