title: Enhancing Virion Tethering by BST2 Sensitizes Productively and Latently HIV-infected T cells to ADCC Mediated by Broadly Neutralizing Antibodies.
abstract: Binding of anti-HIV antibodies (Abs) to envelope (Env) glycoproteins on infected cells can mark them for elimination via antibody-dependent cell-mediated cytotoxicity (ADCC). BST2, a type I interferon (IFN)-stimulated restriction factor that anchors nascent Env-containing virions at the surface of infected cells has been shown to enhance ADCC functions. In a comprehensive analysis of ADCC potency by neutralizing anti-HIV Abs (NAbs), we show in this study that NAbs are capable of mediating ADCC against HIV-infected T cells with 3BNC117, PGT126 and PG9 being most efficient. We demonstrate that HIV-induced BST2 antagonism effectively attenuates Ab binding and ADCC responses mediated by all classes of NAbs that were tested. Interestingly, IFNα treatment can reverse this effect in a BST2-dependent manner. Importantly, while reactivated latent T cell lines display some susceptibility to ADCC mediated by broadly NAbs, inactivating BST2 viral countermeasures and/or exogenous IFNα augment their elimination. Overall, our findings support the notion that NAbs can induce ADCC. They highlight that while BST2 antagonism by HIV promotes ADCC evasion, strategies aimed at restoring BST2 restriction could improve anti-HIV responses and potentially provide a means to eliminate reactivated cells in latent reservoirs.
authors.affiliation: Institut de Recherches Cliniques de Montréal, Montréal, Québec, H2W 1R7, Canada.
authors.forename: Tram N Q
authors.initials: TN
authors.lastname: Pham
authors.affiliation: Institut de Recherches Cliniques de Montréal, Montréal, Québec, H2W 1R7, Canada.
authors.forename: Sabelo
authors.initials: S
authors.lastname: Lukhele
authors.affiliation: Institut de Recherches Cliniques de Montréal, Montréal, Québec, H2W 1R7, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dallaire
authors.affiliation: Institut de Recherches Cliniques de Montréal, Montréal, Québec, H2W 1R7, Canada.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Perron
authors.affiliation: Institut de Recherches Cliniques de Montréal, Montréal, Québec, H2W 1R7, Canada.|Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, Québec, H3T 1J4, Canada.
authors.forename: Éric A
authors.initials: ÉA
authors.lastname: Cohen
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D014771:Virion / Q000276:immunology*; D017735:Virus Latency / Q000276:immunology*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D057134:Antibodies, Neutralizing; D015703:Antigens, CD; D058851:GPI-Linked Proteins; D015483:HIV Antibodies; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2