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T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis

Brenchley, J. M., Hill, B. J., Ambrozak, D. R., Price, David, Guenaga, F. J., Casazza, J. P., Kuruppu, J., Yazdani, J., Migueles, S. A., Connors, M., Roederer, M., Douek, D. C. and Koup, R. A. 2004. T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis. Journal of Virology 78 (3) , pp. 1160-1168. 10.1128/JVI.78.3.1160-1168.2004

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Abstract

Identification of T-cell subsets that are infected in vivo is essential to understanding the pathogenesis of human immunodeficiency virus (HIV) disease; however, this goal has been beset with technical challenges. Here, we used polychromatic flow cytometry to sort multiple T-cell subsets to 99.8% purity, followed by quantitative PCR to quantify HIV gag DNA directly ex vivo. We show that resting memory CD4+ T cells are the predominantly infected cells but that terminally differentiated memory CD4+ T cells contain 10-fold fewer copies of HIV DNA. Memory CD8+ T cells can also be infected upon upregulation of CD4; however, this is infrequent and HIV-specific CD8+ T cells are not infected preferentially. Naïve CD4+ T-cell infection is rare and principally confined to those peripheral T cells that have proliferated. Furthermore, the virus is essentially absent from naïve CD8+ T cells, suggesting that the thymus is not a major source of HIV-infected T cells in the periphery. These data illuminate the underlying mechanisms that distort T-cell homeostasis in HIV infection.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: American Society for Microbiology
ISSN: 0022-538X
Date of First Compliant Deposit: 23 March 2018
Date of Acceptance: 7 October 2003
Last Modified: 27 Mar 2018 14:46
URI: http://orca.cf.ac.uk/id/eprint/110127

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