Broadly neutralizing antibodies that inhibit HIV-1 cell to cell transmission
| Autor: | Olivier Schwartz, Florian Klein, Caroline Eden, Réjane Rua, Michel C. Nussenzweig, Joshua A. Horwitz, Marine Malbec, Johannes F. Scheid, Ari Halper-Stromberg, Françoise Porrot, Hugo Mouquet |
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| Přispěvatelé: | Virus et Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Cellule Pasteur UPMC, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris], Laboratory of Molecular Immunology, Rockefeller University [New York], Réponse humorale aux pathogènes, Howard Hughes Medical Institute (HHMI), O. Schwartz was supported by grants from the Agence Nationale de Recherchesur le Sida, Sidaction, AREVA Foundation, the Vaccine Research Institute, the LabexIBEID program, the FP7 program HIT Hidden HIV (Health-F3-2012-305762), andInstitut Pasteur. M. Malbec was supported by fellowships from Sidaction, Fonds dedotation Pierre Bergé, and Fondation pour la Recherche Médicale. H. Mouquet wassupported by the Milieu Intérieur program (ANR-10-LABX-69-01). M.C. Nussenzweigwas supported by grants from the Bill and Melinda Gates Foundation (Collaborationfor AIDS Vaccine Discovery grant 38619s) and the Center for HIV/AIDS VaccineImmunology and Immunogen Discovery grant AI 100663-01, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP) |
| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Time Factors viruses HIV Infections MESH: Microscopy Fluorescence HIV Antibodies V3 loop MESH: Antibodies Neutralizing Cell to cell transmission Immunology and Allergy MESH: Inhibitory Concentration 50 0303 health sciences MESH: Dendritic Cells MESH: HIV Transmission (medicine) virus diseases MESH: CD4-Positive T-Lymphocytes MESH: HIV Infections 3. Good health MESH: HEK293 Cells [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology MESH: Virion [SDV.IMM]Life Sciences [q-bio]/Immunology Antibody Glycan Immunology Biology MESH: Coculture Techniques Inhibitory Concentration 50 03 medical and health sciences Humans Potency 030304 developmental biology MESH: Humans MESH: HIV Antibodies 030306 microbiology MESH: Time Factors HEK 293 cells Virion Brief Definitive Report HIV Dendritic Cells Antibodies Neutralizing Virology Coculture Techniques HEK293 Cells Microscopy Fluorescence Cell culture MESH: HeLa Cells biology.protein HeLa Cells |
| Zdroj: | Journal of Experimental Medicine Journal of Experimental Medicine, Rockefeller University Press, 2013, 210 (13), pp.2813-21. ⟨10.1084/jem.20131244⟩ The Journal of Experimental Medicine Journal of Experimental Medicine, 2013, 210 (13), pp.2813-21. ⟨10.1084/jem.20131244⟩ |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20131244 |
| Popis: | A subset of broadly neutralizing anti-HIV antibodies inhibits cell to cell transmission of the virus. The neutralizing activity of anti–HIV-1 antibodies is typically measured in assays where cell-free virions enter reporter cell lines. However, HIV-1 cell to cell transmission is a major mechanism of viral spread, and the effect of the recently described broadly neutralizing antibodies (bNAbs) on this mode of transmission remains unknown. Here we identify a subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes. These antibodies target either the CD4-binding site (NIH45-46 and 3BNC60) or the glycan/V3 loop (10-1074 and PGT121) on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. These antibodies accumulate at virological synapses and impair the clustering and fusion of infected and target cells and the transfer of viral material to uninfected T cells. In addition, they block viral cell to cell transmission to plasmacytoid DCs and thereby interfere with type-I IFN production. Thus, only a subset of bNAbs can efficiently prevent HIV-1 cell to cell transmission, and this property should be considered an important characteristic defining antibody potency for therapeutic or prophylactic antiviral strategies. |
| Databáze: | OpenAIRE |
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