Evidence map›Paper›PMID 28003492›Full record

ArticleJournal of virology2017

Residues in the gp41 Ectodomain Regulate HIV-1 Envelope Glycoprotein Conformational Transitions Induced by gp120-Directed Inhibitors.

Beatriz Pacheco, Nirmin Alsahafi, Olfa Debbeche, Jérémie Prévost, Shilei Ding, Jean-Philippe Chapleau, Alon Herschhorn, Navid Madani, Amy Princiotto, Bruno Melillo and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.4field-weighted citation impact, top 7% of its field
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

47 citing papers in PubMed, 64 citations in OpenAlex.

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  16. HIV-1-Infected CD4Journal of immunology (Baltimore, Md. : 1950) · 2022
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 2 countries.

Beatriz PachecoCentre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
Nirmin AlsahafiCentre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
Olfa DebbecheCentre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
Jérémie PrévostCentre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
Shilei DingCentre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
Jean-Philippe ChapleauCentre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
Alon HerschhornDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Navid MadaniDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Amy PrinciottoDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Bruno MelilloDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Christopher GuDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Xin ZengDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Youdong MaoDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Amos B SmithDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Joseph SodroskiDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA joseph_sodroski@dfci.harvard.edu andres.finzi@umontreal.ca.
Andrés FinziCentre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada joseph_sodroski@dfci.harvard.edu andres.finzi@umontreal.ca.
Dana-Farber Cancer Institute · USCentre Hospitalier de l’Université de Montréal · CAUniversity of Pennsylvania · USMcGill University · CAUniversité de Montréal · CA

Funding

Viral Sequencing CoreU19AI067854 · NIAID · DUKE UNIVERSITY · PI BHARDWAJ, NINA · 2006 to 2011
$290.5M
Understanding 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
$31.2M
Viral and Host Determinants of HIV-1 TransmissionU01AI067854 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F · 2005 to 2005
$14.9M
HIV-1 ENVELOPE GLYCOPROTEINSR37AI024755 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1996 to 2015
$11.6M
Conformational Landscape of the HIV-1 Envelope GlycoproteinsR01AI124982 · NIAID · DANA-FARBER CANCER INST · PI SODROSKI, JOSEPH G · 2016 to 2025
$6.7M
Single-particle Reconstruction of HIV-1 Envelope Glycoprotein TrimersR01AI093256 · NIAID · DANA-FARBER CANCER INST · PI SODROSKI, JOSEPH G · 2011 to 2015
$2.2M
Design of dendrimeric HIV-1 transmission inhibitors targeting gp120 Phe-43 cavityR56AI090682 · NIAID · DANA-FARBER CANCER INST · PI MADANI, NAVID · 2010 to 2010
$576k
CIHR 352417NIAID NIH HHS R01 AI093256NIAID NIH HHS R01 AI124982NIAID NIH HHS R37 AI024755NIAID NIH HHS R56 AI090682NIAID NIH HHS U01 AI067854NIAID NIH HHS U19 AI067854NIGMS NIH HHS P01 GM056550
6 · The paper itself

Abstract

Interactions between the gp120 and gp41 subunits of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer maintain the metastable unliganded form of the viral spike. Binding of gp120 to the receptor, CD4, changes the Env conformation to promote gp120 interaction with the second receptor, CCR5 or CXCR4. CD4 binding also induces the transformation of Env into the prehairpin intermediate, in which the gp41 heptad repeat 1 (HR1) coiled coil is assembled at the trimer axis. In nature, HIV-1 Envs must balance the requirements to maintain the noncovalent association of gp120 with gp41 and to evade the host antibody response with the need to respond to CD4 binding. Here we show that the gp41 HR1 region contributes to gp120 association with the unliganded Env trimer. Changes in particular amino acid residues in the gp41 HR1 region decreased the efficiency with which Env moved from the unliganded state. Thus, these gp41 changes decreased the sensitivity of HIV-1 to cold inactivation and ligands that require Env conformational changes to bind efficiently. Conversely, these gp41 changes increased HIV-1 sensitivity to small-molecule entry inhibitors that block Env conformational changes induced by CD4. Changes in particular gp41 HR1 amino acid residues can apparently affect the relative stability of the unliganded state and CD4-induced conformations. Thus, the gp41 HR1 region contributes to the association with gp120 and regulates Env transitions from the unliganded state to downstream conformations.

Indexed as

Amino Acid MotifsAnimalsAnti-HIV AgentsDogsHEK293 CellsHIV-1HIV Envelope Protein gp120HIV Envelope Protein gp41HumansPiperazinesAnti-HIV AgentsBMS 806gp120 protein, Human immunodeficiency virus 1gp41 protein, Human immunodeficiency virus 1HIV Envelope Protein gp120HIV Envelope Protein gp41Piperazinesantibody resistancegp120gp41HIV-1HR1intrinsic envelope reactivitysoluble CD4

Identifiers

PMID28003492
PMCPMC5309946
OpenAlexW2564058179

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.