The persistence of the HIV reservoir in infected individuals is a major obstacle to the development of a cure for HIV1,2,3. 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.
We thank the participants enrolled in this study. We thank members of the Molecular Virology laboratory for critical reading of the manuscript, J. Venables for editing the manuscript, MRI platform for FACSAria cell sorting. We are grateful to J.-F. Delfraissy and F. Barré-Sinoussi for their continuous support. This work was supported by grants from the European FP7 contract 305762, MSDAvenir, ANRS and FRM ‘équipe labéllisée’ and Labex EpiGenMed to M.B. G.P was supported by FRM fellowships; B.D. and R.R. by ANRS fellowships. T.B. was supported by a Vaccine Research Institute (VRI) fellowship. O.S was supported by grants from ANRS, VRI, Labex IBEID, Sidaction, European FP7 contract 305762 and Institut Pasteur.
Extended data figures
This file contains Supplementary Tables 3 and 4.