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

Nature volume 543, pages 564567 (23 March 2017) | Download Citation

  • A Corrigendum to this article was published on 28 June 2017


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.

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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.

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Author notes

    • Benjamin Descours
    •  & Gaël Petitjean

    These authors contributed equally to this work.


  1. Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, UMR9002, CNRS, Université de Montpellier, Montpellier, France

    • Benjamin Descours
    • , Gaël Petitjean
    • , Raoul Raffel
    •  & Monsef Benkirane
  2. Vaccine Research Institute, Université Paris-Est, Faculté de Médecine, INSERM U955, and Assistance Publique-Hôpitaux de Paris, Groupe Henri-Mondor Albert-Chenevier, Service d’Immunologie Clinique, Créteil, France

    • José-Luis López-Zaragoza
    • , Timothée Bruel
    • , Christine Lacabaratz
    • , Yves Levy
    • , Olivier Schwartz
    •  & Jean Daniel Lelievre
  3. Inserm, U955, Equipe 16, Créteil, France

    • José-Luis López-Zaragoza
    • , Christine Lacabaratz
    • , Yves Levy
    •  & Jean Daniel Lelievre
  4. AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d’Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France

    • José-Luis López-Zaragoza
    • , Christine Lacabaratz
    • , Yves Levy
    •  & Jean Daniel Lelievre
  5. Institut Pasteur, Virus and Immunity Unit, URA CNRS 3015, Paris, France

    • Timothée Bruel
    •  & Olivier Schwartz
  6. Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France

    • Christina Psomas
    •  & Jacques Reynes


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M.B. conceived the study. M.B., G.P. and B.D. designed experiments, interpreted data and wrote the paper. R.R. analysed the RNA-seq data. T.B. and O.S. performed highly sensitive p24 assays. J.D.L., J.-L.L.-Z., C.L., C.P., J.R. and Y.L. recruited participants and collected blood samples. All the authors read and approved the final manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Benjamin Descours or Gaël Petitjean or Monsef Benkirane.

Reviewer Information Nature thanks N. Chomont, F. Nimmerjahn, D. Richman, G. Silvestri and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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