ArticleCell reports2022
HIV-1 Vpu restricts Fc-mediated effector functions in vivo.
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Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24citing papers in PubMed
2.0field-weighted citation impact, top 11% of its field
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- Extended hinge length of human IgG3-like antibody enhances early antiviral activity of VRC01 in SHIV-infected rhesus macaques.Journal of virology · 2026Article
- mGem: Opening Env and harnessing NK cell effector functions to eliminate HIV-1-infected cells.mBio · 2026Review
- The asymmetric opening of HIV-1 Env by a potent CD4 mimetic enables anti-coreceptor binding site antibodies to mediate ADCC.Nature communications · 2025Article
- Effects and mechanisms of monoclonal and polyclonal human antibodies in protection of humanized mice from HIV-1 challenge.bioRxiv : the preprint server for biology · 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
- Unpredicted Protective Function of Fc-Mediated Inhibitory Antibodies for HIV and SARS-CoV-2 Vaccines.The Journal of infectious diseases · 2025Review
- Understanding the performance of HIV-1 viral vector vaccines: adenovirus and poxvirus case studies.Frontiers in immunology · 2025Review
- Viral glycoprotein-mediated entry and antibody-mediated immunity in HIV-1 and SARS-CoV-2 infection.Frontiers in immunology · 2025Review
- Optimization of a Piperidine CD4-Mimetic Scaffold Sensitizing HIV-1 Infected Cells to Antibody-Dependent Cellular Cytotoxicity.ACS medicinal chemistry letters · 2024Article
- Article
- 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
- 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
- Article
- The combination of three CD4-induced antibodies targeting highly conserved Env regions with a small CD4-mimetic achieves potent ADCC activity.bioRxiv : the preprint server for biology · 2024Article
- Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in presence of CD4-mimetics.medRxiv : the preprint server for health sciences · 2024Article
- Potent antibody-dependent cellular cytotoxicity of a V2-specific antibody is not sufficient for protection of macaques against SIV challenge.PLoS pathogens · 2024Article
- Excess BAFF May Impact HIV-1-Specific Antibodies and May Promote Polyclonal Responses Including Those from First-Line Marginal Zone B-Cell Populations.Current issues in molecular biology · 2023Article
- Article
Corrections and comments
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Authors and funding
23 authors at 10 institutions in 3 countries.
Jérémie PrévostCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada. Electronic address: jeremie.prevost@umontreal.ca.
Sai Priya AnandCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
Jyothi Krishnaswamy RajashekarDepartment of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06510, USA.
Li ZhuDepartment of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06510, USA.
Jonathan RichardCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
Guillaume GoyetteCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
Halima MedjahedCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
Gabrielle Gendron-LepageCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
Hung-Ching ChenDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
Yaozong ChenInfectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.
Joshua A HorwitzLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Michael W GrunstDepartment of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06510, USA.
Susan Zolla-PaznerDepartment of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Barton F HaynesDuke Human Vaccine Institute, Departments of Medicine and Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), Duke University, Durham, NC 27710, USA.
Dennis R BurtonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02139, USA.
Richard A FlavellDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
Frank KirchhoffInstitute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Beatrice H HahnDepartments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6076, USA.
Amos B SmithDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
Marzena PazgierInfectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.
Michel C NussenzweigLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Priti KumarDepartment of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06510, USA.
Andrés FinziCentre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada. Electronic address: andres.finzi@umontreal.ca.
Centre Hospitalier de l’Université de Montréal · CAYale University · USUniversity of Pennsylvania · USRockefeller University · USUniformed Services University of the Health Sciences · USDuke University · USIcahn School of Medicine at Mount Sinai · USMcGill University · CARagon Institute of MGH, MIT and Harvard · USUniversität Ulm · DE
Funding
Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6MVirus and Antibody Gene Sequencing CoreP01AI131251 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Kevin Wiehe · 2017 to 2026
$40.7MUnderstanding Envelope Function in HIV-1 Infection: The Design, Synthesis and Validation of Small Molecule HIV-1 Env InhibitorsP01GM056550 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI HENDRICKSON, WAYNE A. · 1997 to 2018
$31.2MERASE HIV: Enterprise for Research and Advancements to Stop and Eradicate HIVUM1AI164562 · NIAID · EMORY UNIVERSITY · PI Deanna A Kulpa, Mirko Paiardini · 2021 to 2026
$30.0MVirus TransmissionP50AI150464 · NIAID · UNIVERSITY OF UTAH · PI HOPE, THOMAS · 2019 to 2021
$14.9MUnderstanding Envelope Function in HIV-1 Infection: The Design, Synthesis and Validation of Small Molecule HIV-1 Env InhibitorsP01AI150471 · NIAID · DREXEL UNIVERSITY · PI CHAIKEN, IRWIN M, MOTHES, WALTHER H · 2019 to 2022
$7.8MOptimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogensR37AI150590 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Beatrice H Hahn · 2019 to 2026
$6.9MNatural SIV Reservoirs and Human Zoonotic RiskR01AI050529 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HAHN, BEATRICE H · 2001 to 2022
$6.1MExploring HIV-1 Env open conformations for therapeutic interventionR01AI150322 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Andres Finzi, James B Munro · 2020 to 2026
$4.2MTargeting the HIV-1 reservoir at cART initiation with CD4-mimetic interventionsR01AI186809 · NIAID · YALE UNIVERSITY · PI Priti Kumar, JOSEPH G SODROSKI · 2024 to 2026
$4.0MAssessing ADCC and Fc-mediated Protection against HIVR01AI148379 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI EVANS, DAVID T, FINZI, ANDRES · 2019 to 2023
$3.8MT cell-targeted lentiviral vectors with Cas9/RNP for the in vivo gene therapy of HIV-AIDSR01AI145164 · NIAID · YALE UNIVERSITY · PI KUMAR, PRITI · 2019 to 2024
$3.7MNIAID NIH HHS P01 AI131251NIAID NIH HHS P01 AI150471NIAID NIH HHS P50 AI150464NIAID NIH HHS R01 AI050529NIAID NIH HHS R01 AI116274NIAID NIH HHS R01 AI129769NIAID NIH HHS R01 AI145164NIAID NIH HHS R01 AI148379NIAID NIH HHS R01 AI150322NIAID NIH HHS R01 AI186809NIAID NIH HHS R33 AI122384NIAID NIH HHS R37 AI150590NIAID NIH HHS UM1 AI144462NIAID NIH HHS UM1 AI164562NIGMS NIH HHS P01 GM056550
Abstract
Non-neutralizing antibodies (nnAbs) can eliminate HIV-1-infected cells via antibody-dependent cellular cytotoxicity (ADCC) and were identified as a correlate of protection in the RV144 vaccine trial. Fc-mediated effector functions of nnAbs were recently shown to alter the course of HIV-1 infection in vivo using a vpu-defective virus. Since Vpu is known to downregulate cell-surface CD4, which triggers conformational changes in the viral envelope glycoprotein (Env), we ask whether the lack of Vpu expression was linked to the observed nnAbs activity. We find that restoring Vpu expression greatly reduces nnAb recognition of infected cells, rendering them resistant to ADCC. Moreover, administration of nnAbs in humanized mice reduces viral loads only in animals infected with a vpu-defective but not with a wild-type virus. CD4-mimetics administration, known to "open" Env and expose nnAb epitopes, renders wild-type viruses sensitive to nnAbs Fc-effector functions. This work highlights the importance of Vpu-mediated evasion of humoral responses.
Indexed as
HIV-1HIV InfectionsHIV SeropositivityAnimalsAntibodies, NeutralizingAntibody-Dependent Cell CytotoxicityHIV AntibodiesHumansMiceAntibodies, NeutralizingHIV AntibodiesADCCbroadly neutralizing antibodiesCD4 mimeticsCP: ImmunologyEnvFc-effector functionsHIV-1humanized miceimmune evasionnon-neutralizing antibodiesVpu
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