title: The HIV-1 gp120 CD4-bound conformation is preferentially targeted by antibody-dependent cellular cytotoxicity-mediating antibodies in sera from HIV-1-infected individuals.
abstract: Recent studies have linked antibody Fc-mediated effector functions with protection or control of human immunodeficiency type 1 (HIV-1) and simian immunodeficiency (SIV) infections. Interestingly, the presence of antibodies with potent antibody-dependent cellular cytotoxicity (ADCC) activity in the Thai RV144 vaccine trial was suggested to correlate with decreased HIV-1 acquisition risk. These antibodies recently were found to recognize HIV envelope (Env) epitopes exposed upon Env-CD4 interaction. CD4 downregulation by Nef and Vpu, as well as Vpu-mediated BST-2 antagonism, were reported to modulate exposure of those CD4-induced HIV-1 Env epitopes and were proposed to play a role in reducing the susceptibility of infected cells to ADCC mediated by this class of antibodies. Here, we report the high prevalence of antibodies recognizing CD4-induced HIV-1 Env epitopes in sera from HIV-1-infected individuals, which correlated with their ability to mediate ADCC responses against HIV-1-infected cells, exposing these Env epitopes at the cell surface. Furthermore, our results indicate that Env variable regions V1, V2, V3, and V5 do not represent a major determinant for ADCC responses mediated by sera from HIV-1-infected individuals. Altogether, these findings suggest that HIV-1 tightly controls the exposure of certain Env epitopes at the surface of infected cells in order to prevent elimination by Fc-effector functions.
  
  
  OBJECTIVE
  Here, we identified a particular conformation of HIV-1 Env that is specifically targeted by ADCC-mediating antibodies present in sera from HIV-1-infected individuals. This observation suggests that HIV-1 developed sophisticated mechanisms to minimize the exposure of these epitopes at the surface of infected cells.
authors.affiliation: Centre de Recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Maxime
authors.initials: M
authors.lastname: Veillette
authors.affiliation: Centre de Recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Coutu
authors.affiliation: Centre de Recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Richard
authors.affiliation: Centre de Recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Laurie-Anne
authors.initials: LA
authors.lastname: Batraville
authors.affiliation: Centre de Recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Olina
authors.initials: O
authors.lastname: Dagher
authors.affiliation: Department of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bernard
authors.affiliation: Centre de Recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Cécile
authors.initials: C
authors.lastname: Tremblay
authors.affiliation: Centre de Recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.affiliation: Centre de Recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Roger
authors.affiliation: Centre de Recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada andres.finzi@umontreal.ca.
authors.forename: Andrés
authors.initials: A
authors.lastname: Finzi
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D015704:CD4 Antigens / Q000378:metabolism*; D015331:Cohort Studies; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D011485:Protein Binding
chemical_list: D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1