Evidence map›Paper›PMID 39253431›Full record

ArticlebioRxiv : the preprint server for biology2024

The asymmetric opening of HIV-1 Env by a potent CD4 mimetic enables anti-coreceptor binding site antibodies to mediate ADCC.

Jonathan Richard, Michael W Grunst, Ling Niu, Marco A Díaz-Salinas, William D Tolbert, Lorie Marchitto, Fei Zhou, Catherine Bourassa, Derek Yang, Ta Jung Chiu and 20 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors.

Jonathan RichardCentre de Recherche du CHUM, Montréal, Québec, Canada.
Michael W GrunstDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
Ling NiuInfectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Marco A Díaz-SalinasDepartment of Microbiology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
William D TolbertInfectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Lorie MarchittoCentre de Recherche du CHUM, Montréal, Québec, Canada.
Fei ZhouUnit on Structural Biology, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.
Catherine BourassaCentre de Recherche du CHUM, Montréal, Québec, Canada.
Derek YangDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Ta Jung ChiuDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Hung-Ching ChenDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Mehdi BenlarbiCentre de Recherche du CHUM, Montréal, Québec, Canada.
Guillaume-Beaudoin-Buissières
Suneetha GottumukkalaInfectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Wenwei LiDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
Katrina DionneCentre de Recherche du CHUM, Montréal, Québec, Canada.
Étienne BélangerCentre de Recherche du CHUM, Montréal, Québec, Canada.
Debashree ChatterjeeCentre de Recherche du CHUM, Montréal, Québec, Canada.
Halima MedjahedCentre de Recherche du CHUM, Montréal, Québec, Canada.
Wayne A HendricksonDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
Joseph SodroskiDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Zabrina C LangLaboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, USA.
Abraham J MortonLaboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, USA.
Rick K HuangLaboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, USA.
Doreen MatthiesUnit on Structural Biology, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.ORCID 0000-0001-9221-4484
Amos B SmithDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Walther MothesDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
James B MunroDepartment of Microbiology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.ORCID 0000-0001-7634-4633
Marzena PazgierInfectious Diseases Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Andrés FinziCentre de Recherche du CHUM, Montréal, Québec, Canada.

Funding

ERASE HIV: Enterprise for Research and Advancements to Stop and Eradicate HIVUM1AI164562 · NIAID · EMORY UNIVERSITY · PI Deanna A Kulpa, Mirko Paiardini · 2021 to 2026
$30.0M
Structure-Function Analytics CoreP01AI162242 · NIAID · DUKE UNIVERSITY · PI TOMARAS, GEORGIA DORIS · 2021 to 2025
$22.2M
Towards high-resolution structural biology of membrane protein complexes in their native lipid environmentZIAHD008998 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MATTHIES, DOREEN · 2021 to 2025
$10.7M
Understanding 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
$7.8M
Exploring HIV-1 Env open conformations for therapeutic interventionR01AI150322 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Andres Finzi, James B Munro · 2020 to 2026
$4.2M
Identifying vulnerabilities in the long-lived HIV reservoir to accelerate its decayR01AI176531 · NIAID · FRED HUTCHINSON CANCER CENTER · PI Nicolas Chomont, ANN C DUERR · 2023 to 2026
$4.1M
Targeting the HIV-1 reservoir at cART initiation with CD4-mimetic interventionsR01AI186809 · NIAID · YALE UNIVERSITY · PI Priti Kumar, JOSEPH G SODROSKI · 2024 to 2026
$4.0M
Assessing ADCC and Fc-mediated Protection against HIVR01AI148379 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI EVANS, DAVID T, FINZI, ANDRES · 2019 to 2023
$3.8M
Predoctoral Training Program in VirologyT32AI055403 · NIAID · YALE UNIVERSITY · PI KUMAR, PRITI, MOTHES, WALTHER H · 2003 to 2024
$3.6M
Probing functional HIV-1 envelope glycoprotein conformations with novel potent CD4-mimetic compoundsR01AI176904 · NIAID · DANA-FARBER CANCER INST · PI WAYNE A. HENDRICKSON, WALTHER H MOTHES · 2023 to 2026
$3.4M
HIV-1 Env protein structure and function assessed by parallel smFRET and cryoETR37AI150560 · NIAID · YALE UNIVERSITY · PI WALTHER H MOTHES · 2023 to 2026
$3.2M
A new strategy to eliminate HIV-1-infected cells by unlocking the Env trimerR01AI174908 · NIAID · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI Marzena Elzbieta Pazgier · 2023 to 2026
$2.8M
Intramural NIH HHS ZIA HD008998NIAID NIH HHS F31 AI176650NIAID NIH HHS P01 AI150471NIAID NIH HHS P01 AI162242NIAID NIH HHS R01 AI148379NIAID NIH HHS R01 AI150322NIAID NIH HHS R01 AI174908NIAID NIH HHS R01 AI176531NIAID NIH HHS R01 AI176904NIAID NIH HHS R01 AI186809NIAID NIH HHS R37 AI150560NIAID NIH HHS T32 AI055403NIAID NIH HHS UM1 AI164562
6 · The paper itself

Abstract

HIV-1 envelope glycoproteins (Env) from primary HIV-1 isolates typically adopt a pretriggered "closed" conformation that resists to CD4-induced (CD4i) non-neutralizing antibodies (nnAbs) mediating antibody-dependent cellular cytotoxicity (ADCC). CD4-mimetic compounds (CD4mcs) "open-up" Env allowing binding of CD4i nnAbs, thereby sensitizing HIV-1-infected cells to ADCC. Two families of CD4i nnAbs, the anti-cluster A and anti-coreceptor binding site (CoRBS) Abs, are required to mediate ADCC in combination with the indane CD4mc BNM-III-170. Recently, new indoline CD4mcs with improved potency and breadth have been described. Here, we show that the lead indoline CD4mc, CJF-III-288, sensitizes HIV-1-infected cells to ADCC mediated by anti-CoRBS Abs alone, contributing to improved ADCC activity. Structural and conformational analyses reveal that CJF-III-288, in combination with anti-CoRBS Abs, potently stabilizes an asymmetric "open" State-3 Env conformation, This Env conformation orients the anti-CoRBS Ab to improve ADCC activity and therapeutic potential.

Identifiers

PMID39253431
PMCPMC11383012

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.