title: Role of HIV-1 Envelope Glycoproteins Conformation and Accessory Proteins on ADCC Responses.
abstract: The role of antibody Fc-mediated effector functions in controlling or preventing infections by human immunodeficiency type 1 (HIV-1) and simian immunodeficiency (SIV) viruses has been recently highlighted in multiple studies. One of those effector functions, antibody-dependent cellular cytotoxicity (ADCC) was suggested as correlating with decreased HIV-1 acquisition risk in the recent Thai RV144 vaccine trial. RV144-elicited antibodies with potent ADCC activity were recently found to recognize HIV envelope (Env) epitopes exposed upon Env-CD4 interaction. However, HIV-1 efficiently limits the exposure of those epitopes by strongly downregulating CD4 by both Nef and Vpu accessory proteins, as well as indirectly preventing the accumulation of Env at the cell surface by Vpu-mediated BST-2 antagonism. These accessory proteins were thus proposed to play a critical role in decreasing the susceptibility of HIV-infected cells to elimination by ADCC. In this review we will summarize these recent findings and discuss the critical role that HIV-1 envelope glycoproteins conformation plays on ADCC responses, how these responses can be measured in the laboratory, the role of HIV-1-transmission on ADCC responses and how this knowledge can be used to develop new strategies aimed at targeting HIV-1-infected cells.
authors: Maxime
authors: M
authors: Veillette
authors: Jonathan
authors: J
authors: Richard
authors: Marzena
authors: M
authors: Pazgier
authors: George K
authors: GK
authors: Lewis
authors: Matthew S
authors: MS
authors: Parsons
authors: Centre de recherche du CHUM (CRCHUM), 900 St-Denis street, Tour Viger, R09.420, Montreal, Quebec, H2X 0A9, Canada. andres.finzi@umontreal.ca.
authors: Andrés
authors: A
authors: Finzi
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D002450:Cell Communication; D000939:Epitopes / Q000276:immunology; D005470:Fluorometry; D053804:Granzymes / Q000378:metabolism; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D016915:AIDS Vaccines; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D053804:Granzymes