ArticleProceedings of the National Academy of Sciences of the United States of America2015
CD4 mimetics sensitize HIV-1-infected cells to ADCC.
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Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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116citing papers in PubMed, 1 pooled it
9.7field-weighted citation impact, top 1% of its field
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- Article
- Rapid and robust immune response boosting with potent, next-generation adjuvant in viral vector-primed primates.Journal of virology · 2026Article
- HIV tri-specific killer engagers directly enhance NK cell function and safely expand NK cells in vivo.Cell reports. Medicine · 2026Article
- Nef and Vpu protect infected cells from ADCP mediated by plasma from people with HIV-1.bioRxiv : the preprint server for biology · 2026Article
- mGem: Opening Env and harnessing NK cell effector functions to eliminate HIV-1-infected cells.mBio · 2026Review
- Retinoids enhance NK effector function against HIV-infected CD4 T cells.Journal of virology · 2026Article
- Conformational dynamics of the HIV-1 envelope glycoprotein from CRF01_AE is associated with susceptibility to antibody-dependent cellular cytotoxicity.Journal of virology · 2026Article
- The asymmetric opening of HIV-1 Env by a potent CD4 mimetic enables anti-coreceptor binding site antibodies to mediate ADCC.Nature communications · 2025Article
- Factors associated with resistance of HIV-1 reservoir viruses to neutralization by autologous IgG antibodies.The Journal of clinical investigation · 2025Article
- CD4-mimetics sensitize HIV-infected cells to ADCC mediated by plasma from persons with early-stage HIV-1 infection.Journal of virology · 2025Article
- Safety, pharmacokinetics, and biological activity of CD4-mimetic BNM-III-170 in SHIV-infected rhesus macaques.Journal of virology · 2025Article
- Association between HIV-1 Nef-mediated MHC-I downregulation and the maintenance of the replication-competent latent viral reservoir in individuals with virally suppressed HIV-1 in Uganda: an exploratory cohort study.The Lancet. Microbe · 2025Article
- Molecular parameters governing antibody FcγR signaling and effector functions in the context of HIV envelope.Cell reports · 2025Article
- Optimization of a Piperidine CD4-Mimetic Scaffold Sensitizing HIV-1 Infected Cells to Antibody-Dependent Cellular Cytotoxicity.ACS medicinal chemistry letters · 2024Article
- Article
- Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in the presence of CD4-mimetics.Journal of virology · 2024Article
- The combination of three CD4-induced antibodies targeting highly conserved Env regions with a small CD4-mimetic achieves potent ADCC activity.Journal of virology · 2024Article
- Potent broadly neutralizing antibodies mediate efficient antibody-dependent phagocytosis of HIV-infected cells.PLoS pathogens · 2024Article
- Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 11 institutions in 3 countries.
Jonathan RichardCentre de Recherche du Centre hospitalier de l'Université de Montréal and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada H2X 0A9;
Maxime VeilletteCentre de Recherche du Centre hospitalier de l'Université de Montréal and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada H2X 0A9;
Nathalie BrassardCentre de Recherche du Centre hospitalier de l'Université de Montréal and.
Shilpa S IyerDepartment of Medicine and Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6076;
Michel RogerCentre de Recherche du Centre hospitalier de l'Université de Montréal and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada H2X 0A9;
Loïc MartinCommissariat à l'énergie atomique, Institut de biologie et de technologies de Saclay, Service d'Ingénierie Moléculaire des Protéines, 91191 Gif sur Yvette, France;
Marzena PazgierInstitute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201;
Arne SchönDepartment of Biology, The Johns Hopkins University, Baltimore, MD 21218-2685;
Ernesto FreireDepartment of Biology, The Johns Hopkins University, Baltimore, MD 21218-2685;
Jean-Pierre RoutyDepartment of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4;
Amos B SmithDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323;
Jongwoo ParkDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323;
David M JonesDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323;
Joel R CourterDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323;
Bruno N MelilloDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323;
Daniel E KaufmannCentre de Recherche du Centre hospitalier de l'Université de Montréal and Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139-3583; Department of Medicine, Université de Montréal, Montreal, Quebec, Canada H2X 0A9; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037;
Beatrice H HahnDepartment of Medicine and Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6076; andres.finzi@umontreal.ca bhahn@upenn.edu.
Sallie R PermarDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710;
Barton F HaynesDuke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710;
Navid MadaniDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115; Department of Microbiology and Immunobiology, Division of AIDS, Harvard Medical School, Boston, MA 02115; and Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115.
Joseph G SodroskiDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115; Department of Microbiology and Immunobiology, Division of AIDS, Harvard Medical School, Boston, MA 02115; and Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115.
Andrés FinziCentre de Recherche du Centre hospitalier de l'Université de Montréal and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada H2X 0A9; Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4; andres.finzi@umontreal.ca bhahn@upenn.edu.
University of Pennsylvania · USCentre Hospitalier de l’Université de Montréal · CADuke Medical Center · USJohns Hopkins University · USMcGill University · CAUniversité de Montréal · CACommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRDana-Farber Cancer Institute · USHarvard University · USScripps Research Institute · USUniversity of Maryland, Baltimore · US
Funding
Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2012 to 2018
$204.7MSupport Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5MVirus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6MUnderstanding Envelope Function in HIV-1 Infection: The Design, Synthesis and Validation of Small Molecule HIV-1 Env InhibitorsP01GM056550 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI ABRAMS, CAMERON F · 1997 to 2018
$31.2MHIV-1 ENVELOPE GLYCOPROTEINSR37AI024755 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1996 to 2015
$11.6MImmunoregulatory networks and HIV pathogenesisR01HL092565 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI KAUFMANN, DANIEL E · 2007 to 2015
$3.4MTransmission-blocking potential of novel HIV Env-specific mucosal antibodiesR01AI106380 · NIAID · DUKE UNIVERSITY · PI PERMAR, SALLIE R. · 2013 to 2017
$3.4MRestriction of HIV-1 transmission by type 1 interferonsR01AI114266 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HAHN, BEATRICE H · 2014 to 2018
$3.2MBroadly Neutralizing Monoclonal Antibodies Against HIV-1R01AI087181 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI LEWIS, GEORGE K · 2010 to 2014
$2.7MHarnessing type 1 IFN-stimulated antiviral mechanisms for HIV vaccine designR01AI111789 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HAHN, BEATRICE H · 2014 to 2017
$816kDesign of dendrimeric HIV-1 transmission inhibitors targeting gp120 Phe-43 cavityR56AI090682 · NIAID · DANA-FARBER CANCER INST · PI MADANI, NAVID · 2010 to 2010
$576kROLE OF THE HTLV-III ENVELOPE GLYCOPROTEIN IN VIRUSR01AI024755 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1987 to 1995
–Canadian Institutes of Health Research 119334Canadian Institutes of Health Research 134117Canadian Institutes of Health Research 135349Canadian Institutes of Health Research 291485NHLBI NIH HHS R01 HL092565NHLBI NIH HHS R01HL092565NIAID NIH HHS AI090682NIAID NIH HHS AI100645NIAID NIH HHS AI106380NIAID NIH HHS P30 AI045008NIAID NIH HHS P30AI045008NIAID NIH HHS R01 AI087181NIAID NIH HHS R01AI087181NIAID NIH HHS R01 AI106380NIAID NIH HHS R01 AI111789NIAID NIH HHS R01AI111789NIAID NIH HHS R01 AI114266NIAID NIH HHS R01AI114266NIAID NIH HHS R37 AI024755NIAID NIH HHS R56 AI090682NIAID NIH HHS UM1 AI100645NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1AI100663NIAID NIH HHS UM1AI24755NIGMS NIH HHS GM56550NIGMS NIH HHS P01 GM056550
Abstract
HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by limiting the overall amount of Env at the cell surface. Here we report that small-molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1-infected individuals. Importantly, we identified one CD4 mimetic with the capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells to ADCC killing mediated by autologous sera and effector cells. Thus, CD4 mimetics hold the promise of therapeutic utility in preventing and controlling HIV-1 infection.
Indexed as
Antibody-Dependent Cell CytotoxicityCD4 AntigensCD4-Positive T-Lymphocytesenv Gene Products, Human Immunodeficiency VirusFlow CytometryHEK293 CellsHIV-1HIV InfectionsHumansMutagenesis, Site-DirectedProtein ConformationRecombinant ProteinsCD4 Antigensenv Gene Products, Human Immunodeficiency VirusRecombinant ProteinsADCCCD4 mimeticsenvelope glycoproteinsgp120HIV-1
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