title: CD36-specific antibodies block release of HIV-1 from infected primary macrophages and its transmission to T cells.
abstract: HIV-1-infected macrophages likely represent viral reservoirs, as they accumulate newly formed virions in internal virus-containing compartments (VCCs). However, the nature and biogenesis of VCCs remain poorly defined. We show that upon HIV-1 infection of primary human macrophages, Gag is recruited to preexisting compartments containing the scavenger receptor CD36, which then become VCCs. Silencing of CD36 in HIV-1-infected macrophages decreases the amount of virions released. Strikingly, soluble anti-CD36 antibodies, but not the natural ligands of CD36, inhibit release of virions from HIV-1-infected macrophages and the transmission of virus to CD4(+) T cells. The effect of the antibodies is potent, rapid, and induces the retention of virions within VCCs. Ectopic expression of CD36 in HeLa cells renders them susceptible to the inhibitory effect of the anti-CD36 mAb upon HIV-1 infection. We show that the anti-CD36 mAb inhibits HIV-1 release by clustering newly formed virions at their site of budding, and that signaling via CD36 is not required. Thus, HIV-1 reservoirs in macrophages may be tackled therapeutically using anti-CD36 antibodies to prevent viral dissemination.
authors.affiliation: Institut Curie, Centre de Recherche, F-75248 Paris, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Berre
authors.forename: Raphaël
authors.initials: R
authors.lastname: Gaudin
authors.forename: Bruna
authors.initials: B
authors.lastname: Cunha de Alencar
authors.forename: Marion
authors.initials: M
authors.lastname: Desdouits
authors.forename: Mélanie
authors.initials: M
authors.lastname: Chabaud
authors.forename: Nadia
authors.initials: N
authors.lastname: Naffakh
authors.forename: Marc
authors.initials: M
authors.lastname: Rabaza-Gairi
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Gobert
authors.forename: Mabel
authors.initials: M
authors.lastname: Jouve
authors.forename: Philippe
authors.initials: P
authors.lastname: Benaroch
mesh_terms: D000595:Amino Acid Sequence; D018033:Antibodies, Bispecific; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D018955:CD36 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D014771:Virion / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D019065:Virus Assembly / Q000276:immunology; D057074:Virus Release / Q000276:immunology
chemical_list: D018033:Antibodies, Bispecific; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D016655:HIV Core Protein p24; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C514799:p24 protein, Human Immunodeficiency Virus Type 1