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. 2009 Sep;83(17):8470-81.
doi: 10.1128/JVI.02568-08. Epub 2009 Jun 17.

Analysis of human immunodeficiency virus type 1 viremia and provirus in resting CD4+ T cells reveals a novel source of residual viremia in patients on antiretroviral therapy

Timothy P Brennan  1 , John O Woods, Ahmad R Sedaghat, Janet D Siliciano, Robert F Siliciano, Claus O Wilke
Affiliations

Analysis of human immunodeficiency virus type 1 viremia and provirus in resting CD4+ T cells reveals a novel source of residual viremia in patients on antiretroviral therapy

Timothy P Brennan et al. J Virol. 2009 Sep.

Abstract

Highly active antiretroviral therapy (HAART) can reduce human immunodeficiency virus type 1 (HIV-1) viremia to clinically undetectable levels. Despite this dramatic reduction, some virus is present in the blood. In addition, 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 use 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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Figures

FIG. 1.
FIG. 1.
Phylogenetic analysis of proviral sequences derived from activated and resting CD4+ T cells for two representative patients. The trees were generated by using a classical ML approach and were rooted with an M group ancestral sequence. Red circles refer to proviral sequences derived from activated CD4+ T cells, and blue circles correspond to proviral sequences derived from resting CD4+ T cells. Clusters of five or more identical sequences are boxed. Bootstrap values of 50% or greater are shown. (a) ML tree from a patient with a defined predominant plasma sequence (PPC); (b) ML tree from a patient without a PPC.
FIG. 2.
FIG. 2.
Histogram illustrating the proportion of patients studied that exhibit significant evidence for distinct population structure. Blue bars indicate the number of patients with no significant evidence of population structure. Red bars indicate the number of patients with significant evidence of population structure.
FIG. 3.
FIG. 3.
Phylogenetic analysis of sequences derived from free plasma virus and proviral sequences derived from resting CD4+ T cells for two representative patients. The trees were generated by using a classical ML approach and were rooted with an M group ancestral sequence. Circles refer to proviral sequences derived from resting CD4+ T cells, and triangles correspond to sequences derived from free plasma virus. Clusters of five or more identical sequences are boxed. The colors of the circles and triangles correspond to the time point at which blood was drawn from the patient. Bootstrap values of 50% or greater are shown. (a) ML tree from a patient with a defined predominant plasma sequence (PPC); (b) ML tree from a patient without a PPC.
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References

    1. Bailey, J. R., A. R. Sedaghat, T. Kieffer, T. Brennan, P. K. Lee, M. Wind-Rotolo, C. M. Haggerty, A. R. Kamireddi, Y. Liu, J. Lee, D. Persaud, J. E. Gallant, J. Cofrancesco, Jr., T. C. Quinn, C. O. Wilke, S. C. Ray, J. D. Siliciano, R. E. Nettles, and R. F. Siliciano. 2006. Residual human immunodeficiency virus type 1 viremia in some patients on antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4+ T cells. J. Virol. 806441-6457. - PMC - PubMed
    1. Benjamini, Y., and Y. Hochberg. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. 57289-300.
    1. Blankson, J. N., D. Persaud, and R. F. Siliciano. 2002. The challenge of viral reservoirs in HIV-1 infection. Annu. Rev. Med. 53557-593. - PubMed
    1. Borderia, A. V., F. M. Codoner, and R. Sanjuan. 2007. Selection promotes organ compartmentalization in HIV-1: evidence from gag and pol genes. Evolution 61272-279. - PubMed
    1. Bukrinsky, M. I., T. L. Stanwick, M. P. Dempsey, and M. Stevenson. 1991. Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Science 254423-427. - PMC - PubMed

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