Research Article: Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection

Date Published: October 16, 2015

Publisher: Public Library of Science

Author(s): Natalia Soriano-Sarabia, Nancie M. Archin, Rosalie Bateson, Noelle P. Dahl, Amanda M. Crooks, JoAnn D. Kuruc, Carolina Garrido, David M. Margolis, Guido Silvestri.

http://doi.org/10.1371/journal.ppat.1005201

Abstract

Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection. Despite low or lack of CD4 receptor expression on Vδ2 T cells, infection of these cells has previously been reported. We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo. We assessed the presence of latent HIV infection by measurements of DNA and outgrowth assays within Vδ2 cells in 18 aviremic patients on long-standing antiretroviral therapy. In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.

Partial Text

The infecting HIV genome integrates into host chromatin where, transcriptionally silent and unaffected by antiretroviral therapy (ART), it represents a major challenge towards efforts to eradicate infection [1]. Virologic latency is defined as durable, quiescent infection from which replication-competent HIV can emerge after cell activation. To date, resting memory CD4+ T lymphocytes are the major cell type in which latency has been documented in vivo [2–5]. However, efforts to eradicate HIV infection require the identification of all potential cellular reservoirs and therefore, while conventional αβ T cells, which include resting memory CD4+ T cells, constitute the major subpopulation of T lymphocytes, the γδ T cell population merits study as a potentially important site of latent infection.

We have discovered that peripheral resting Vγ9Vδ2 cells can act as a cellular reservoir of persistent, latent HIV infection. Using a gold-standard coculture assay that defines the presence of latent infection, we find that the frequency of replication-competent virus in these cells is substantial, with virus recovered in as few as 5000 Vδ2 T cells that lack activation markers. This unexpected finding is supported by the detection of HIV DNA within this cell population, implying that at least a fraction of the HIV DNA detected within Vδ2 cells represents replication-competent virus.

 

Source:

http://doi.org/10.1371/journal.ppat.1005201

 

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