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 ORCID: https://orcid.org/0000-0001-9416-2737, 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:	05 May 2023 06:46
URI:	https://orca.cardiff.ac.uk/id/eprint/110127

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