title: CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses.
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.
authors.affiliation: Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, UMR9002, CNRS, Université de Montpellier, Montpellier, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Descours
authors.affiliation: Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, UMR9002, CNRS, Université de Montpellier, Montpellier, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Petitjean
authors.affiliation: 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.|Inserm, U955, Equipe 16, Créteil, France.|AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France.
authors.forename: José-Luis
authors.initials: JL
authors.lastname: López-Zaragoza
authors.affiliation: 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.|Institut Pasteur, Virus and Immunity Unit, URA CNRS 3015, Paris, France.
authors.forename: Timothée
authors.initials: T
authors.lastname: Bruel
authors.affiliation: Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, UMR9002, CNRS, Université de Montpellier, Montpellier, France.
authors.forename: Raoul
authors.initials: R
authors.lastname: Raffel
authors.affiliation: Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Psomas
authors.affiliation: Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.affiliation: 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.|Inserm, U955, Equipe 16, Créteil, France.|AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lacabaratz
authors.affiliation: 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.|Inserm, U955, Equipe 16, Créteil, France.|AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.affiliation: 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.|Institut Pasteur, Virus and Immunity Unit, URA CNRS 3015, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.affiliation: 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.|Inserm, U955, Equipe 16, Créteil, France.|AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France.
authors.forename: Jean Daniel
authors.initials: JD
authors.lastname: Lelievre
authors.affiliation: Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, UMR9002, CNRS, Université de Montpellier, Montpellier, France.
authors.forename: Monsef
authors.initials: M
authors.lastname: Benkirane
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D002455:Cell Division; D002469:Cell Separation; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification; D006801:Humans; D011533:Proviruses / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification; D017452:Receptors, IgG / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D017735:Virus Latency / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG