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

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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. Antiretroviral therapy (ART) has led to a decreased HIV-related morbidity and mortality across the world. While successful ART restores health, it does not cure infection as latent HIV-1 remains integrated within different cell populations, unaffected by ART. To date resting memory CD4+ T cells are the best-characterized cellular reservoir. However, eradication of HIV-1 infection requires the description of all latent cellular reservoirs harboring replication-competent HIV-1. We describe the discovery of an unexpected cellular reservoir within γδ T lymphocytes. This novel reservoir must be considered as strategies to clear latent HIV are developed and tested.

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