Evidence map›Paper›PMID 30944182›Full record

ArticleJournal of virology2019

Effects of the SOS (A501C/T605C) and DS (I201C/A433C) Disulfide Bonds on HIV-1 Membrane Envelope Glycoprotein Conformation and Function.

Hanh T Nguyen, Nirmin Alsahafi, Andrés Finzi, Joseph G Sodroski

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.9field-weighted citation impact, top 30% 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

14 citing papers in PubMed, 17 citations in OpenAlex.

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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

4 authors at 2 institutions in 2 countries.

Hanh T NguyenDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA.
Nirmin AlsahafiDepartment of Microbiology and Immunology, McGill University, Montréal, Quebec, Canada.
Andrés FinziDepartment of Microbiology and Immunology, McGill University, Montréal, Quebec, Canada.
Joseph G SodroskiDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA joseph_sodroski@dfci.harvard.edu.
Dana-Farber Cancer Institute · USMcGill University · CA

Funding

Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI KELSOE, GARNETT H · 2012 to 2018
$204.7M
Understanding 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
$31.2M
Conformational Landscape of the HIV-1 Envelope GlycoproteinsR01AI124982 · NIAID · DANA-FARBER CANCER INST · PI SODROSKI, JOSEPH G · 2016 to 2025
$6.7M
Enrichment of the State-1 Conformation of the HIV-1 Envelope GlycoproteinR01AI145547 · NIAID · DANA-FARBER CANCER INST · PI SODROSKI, JOSEPH G · 2019 to 2021
$2.2M
CIHRNIAID NIH HHS R01 AI124982NIAID NIH HHS R01 AI145547NIAID NIH HHS UM1 AI100645NIGMS NIH HHS P01 GM056550
6 · The paper itself

Abstract

Most broadly neutralizing antibodies and many entry inhibitors target the pretriggered (state 1) conformation of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env). Here we examine two previously reported Env mutants designed to be stabilized in this conformation by the introduction of artificial disulfide bonds: A501C/T605C (called SOS) and I201C/A433C (called DS). SOS Env supported virus entry and cell-cell fusion only after exposure to a reducing agent, dithiothreitol (DTT). Deletion of the Env cytoplasmic tail improved the efficiency with which the SOS Env supported virus infection in a reducing environment. The antigenicity of the SOS Env was similar to that of the unmodified Env, except for greater sensitivity to some state 1-preferring ligands. In contrast, viruses with the DS Env were not infectious, even after DTT treatment. The proteolytic maturation of the DS Env on both cell surfaces and virions was severely compromised compared with that of the unmodified Env. The DS Env exhibited detectable cell-fusing activity when DTT was present. However, the profiles of cell-surface Env recognition and cell-cell fusion inhibition by antibodies differed for the DS Env and the unmodified Env. Thus, the DS Env appears to be stabilized in an off-pathway conformation that is nonfunctional on the virus. The SOS change exerted more subtle, context-dependent effects on Env conformation and function.

Indexed as

Antibodies, NeutralizingDisulfidesenv Gene Products, Human Immunodeficiency VirusGenes, envHEK293 CellsHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV Envelope Protein gp41HumansMembrane GlycoproteinsProtein ConformationStructure-Activity RelationshipViral Envelope ProteinsVirus InternalizationAntibodies, NeutralizingDisulfidesenv Gene Products, Human Immunodeficiency VirusHIV AntibodiesHIV Envelope Protein gp120HIV Envelope Protein gp41Membrane GlycoproteinsViral Envelope ProteinsantibodyEnvHIV-1inhibitormutantretrovirusstructure

Identifiers

PMID30944182
PMCPMC6613753
OpenAlexW2930186558

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.