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CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses.

CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses.
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Descours B, Petitjean G, López-Zaragoza JL, Bruel T, Raffel R, Psomas C, Reynes J, Lacabaratz C, Levy Y, Schwartz O, Lelievre JD, Benkirane M,


Descours B, Petitjean G, López-Zaragoza JL, Bruel T, Raffel R, Psomas C, Reynes J, Lacabaratz C, Levy Y, Schwartz O, Lelievre JD, Benkirane M, (click to view)

Descours B, Petitjean G, López-Zaragoza JL, Bruel T, Raffel R, Psomas C, Reynes J, Lacabaratz C, Levy Y, Schwartz O, Lelievre JD, Benkirane M,

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Nature 2017 03 15() doi 10.1038/nature21710

Abstract

The persistence of the HIV reservoir in infected individuals is a major obstacle to the development of a cure for HIV. Here, using an in vitro model of HIV-infected quiescent CD4 T cells, we reveal a gene expression signature of 103 upregulated genes that are specific for latently infected cells, including genes for 16 transmembrane proteins. In vitro screening for surface expression in HIV-infected quiescent CD4 T cells shows that the low-affinity receptor for the immunoglobulin G Fc fragment, CD32a, is the most highly induced, with no detectable expression in bystander cells. Notably, productive HIV-1 infection of T-cell-receptor-stimulated CD4 T cells is not associated with CD32a expression, suggesting that a quiescence-dependent mechanism is required for its induction. Using blood samples from HIV-1-positive participants receiving suppressive antiretroviral therapy, we identify a subpopulation of 0.012% of CD4 T cells that express CD32a and host up to three copies of HIV DNA per cell. This CD32a(+) reservoir was highly enriched in inducible replication-competent proviruses and can be predominant in some participants. Our discovery that CD32a(+) lymphocytes represent the elusive HIV-1 reservoir may lead to insights that will facilitate the specific targeting and elimination of this reservoir.

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