Evidence map›Paper›PMID 37745449›Full record

ArticlebioRxiv : the preprint server for biology2023

Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted / founder sensitivity to broadly neutralizing antibodies.

Durgadevi Parthasarathy, Karunakar Reddy Pothula, Kim-Marie A Dam, Sneha Ratnapriya, Héctor Cervera Benet, Ruth Parsons, Xiao Huang, Salam Sammour, Katarzyna Janowska, Miranda Harris and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Durgadevi ParthasarathyDivision of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Karunakar Reddy PothulaDuke Human Vaccine Institute, Durham, NC, USA.
Kim-Marie A DamDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Sneha RatnapriyaDivision of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Héctor Cervera BenetDivision of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Ruth ParsonsDuke Human Vaccine Institute, Durham, NC, USA.
Xiao HuangDuke Human Vaccine Institute, Durham, NC, USA.
Salam SammourDuke Human Vaccine Institute, Durham, NC, USA.
Katarzyna JanowskaDuke Human Vaccine Institute, Durham, NC, USA.
Miranda HarrisDivision of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Samuel SaccoDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Joseph SodroskiDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Michael D BridgesJules Stein Eye Institute, University of California, Los Angeles, CA, USA.
Wayne L HubbellJules Stein Eye Institute, University of California, Los Angeles, CA, USA.
Priyamvada AcharyaDuke Human Vaccine Institute, Durham, NC, USA.
Alon HerschhornDivision of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.

Funding

Stuctural basis of bNab activityP01AI100148 · NIAID · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Pamela J Bjorkman · 2013 to 2026
$43.3M
Project 3 - Dynamics of latent HIV-1 reservoirs: High resolution antigenic mapping and strategies to block reboundU54AI170752 · NIAID · DUKE UNIVERSITY · PI Priyamvada Acharya · 2022 to 2026
$32.0M
Virus TransmissionP50AI150464 · NIAID · UNIVERSITY OF UTAH · PI SUNDQUIST, WESLEY I. · 2019 to 2021
$14.9M
Dissecting the mechanisms of HIV resistance in vivo to broadly neutralizing antibodiesU01AI169587 · NIAID · UNIVERSITY OF MINNESOTA · PI Priyamvada Acharya, Brandon James DeKosky · 2022 to 2026
$7.8M
Targeting early metastable intermediates of the SARS-CoV-2 spike for vaccine and therapeutics developmentR01AI145687 · NIAID · DUKE UNIVERSITY · PI Priyamvada Acharya · 2019 to 2026
$6.9M
Dissecting the Conformational Flexibility of HIV-1 Envelope GlycoproteinsR01AI167653 · NIAID · UNIVERSITY OF MINNESOTA · PI HERSCHHORN, ALON · 2022 to 2025
$2.9M
DELINEATION AND VULNERABILITIES OF HIV-1 ESCAPE FROM NEUTRALIZING ANTIBODIESDP2DA049279 · NIDA · UNIVERSITY OF MINNESOTA · PI HERSCHHORN, ALON · 2019 to 2019
$2.3M
NIAID NIH HHS P01 AI100148NIAID NIH HHS P50 AI150464NIAID NIH HHS R01 AI145687NIAID NIH HHS R01 AI167653NIAID NIH HHS U01 AI169587NIAID NIH HHS U54 AI170752NIDA NIH HHS DP2 DA049279
6 · The paper itself

Abstract

HIV-1 envelope glycoproteins (Envs) mediate viral entry and are the sole target of neutralizing antibodies. Envs of most primary HIV-1 strains exist in a closed conformation and occasionally sample more open states. Thus, current knowledge guides immunogen design to mimic the closed Env conformation as the preferred target for eliciting broadly neutralizing antibodies (bnAbs) to block HIV-1 entry. Here we show that Env-preferred conformations of 6 out of 13 (46%) transmitted/founder (T/F) strains tested are incompletely closed. As a result, entry of these T/Fs into target cells is sensitive to antibodies that recognize internal epitopes exposed on open Env conformations. A cryo-electron microscopy structure of unliganded, incompletely closed T/F Envs (1059-SOSIP) at 3.6 Å resolution exhibits an asymmetric configuration of Env protomers with increased sampling of states with incompletely closed trimer apex. Double electron-electron resonance spectroscopy provided further evidence for enriched occupancy of more open Env conformations. Consistent with conformational flexibility, 1059 Envs were associated with resistance to most bnAbs that exhibit reduced potency against functional Env intermediates. To follow the fate of incompletely closed Env in patients, we reconstructed

Identifiers

PMID37745449
PMCPMC10515946

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Registered trials

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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.