Evidence map›Paper›PMID 21471242›Full record

ArticleJournal of virology2011

Enzyme digests eliminate nonfunctional Env from HIV-1 particle surfaces, leaving native Env trimers intact and viral infectivity unaffected.

Ema T Crooks, Tommy Tong, Keiko Osawa, James M Binley

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

81 citing papers in PubMed, 106 citations in OpenAlex.

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21 more citing papers are in PubMed but not listed here.

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 1 country.

Ema T CrooksTorrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA.
Tommy Tong
Keiko Osawa
James M Binley
General Atomics (United States) · USTorrey Pines Institute For Molecular Studies · US

Funding

Pure and Authentic HIV-1 Env ImmunogensR01AI093278 · NIAID · TORREY PINES INST FOR MOLECULAR STUDIES · PI BINLEY, JAMES M · 2011 to 2024
$11.6M
Rescue of broadly neutralizing mAbs using native trimerR01AI100790 · NIAID · TORREY PINES INST FOR MOLECULAR STUDIES · PI BINLEY, JAMES M · 2012 to 2016
$2.3M
SELECTING ENV TRIMERS IN HIV-VLP VACCINE PRESENTATIONSR01AI058763 · NIAID · TORREY PINES INST FOR MOLECULAR STUDIES · PI BINLEY, JAMES M · 2004 to 2007
$1.9M
Stabilizing HIV-1 Trimers by Linking gp120 SubunitsR33AI084714 · NIAID · TORREY PINES INST FOR MOLECULAR STUDIES · PI BINLEY, JAMES M · 2012 to 2014
$957k
Selecting Env Trimers in HIV-VLP Vaccine PresentationsR56AI058763 · NIAID · TORREY PINES INST FOR MOLECULAR STUDIES · PI BINLEY, JAMES M · 2008 to 2009
$591k
Stabilizing HIV-1 Trimers by Linking gp120 SubunitsR21AI084714 · NIAID · TORREY PINES INST FOR MOLECULAR STUDIES · PI BINLEY, JAMES M · 2009 to 2010
$493k
NIAID NIH HHS AI58763NIAID NIH HHS AI84714NIAID NIH HHS R01 AI058763NIAID NIH HHS R01 AI093278NIAID NIH HHS R01 AI100790NIAID NIH HHS R21 AI084714NIAID NIH HHS R33 AI084714NIAID NIH HHS R56 AI058763
6 · The paper itself

Abstract

HIV-1 viruses and virus-like particles (VLPs) bear nonnative "junk" forms of envelope (Env) glycoprotein that may undermine the development of antibody responses against functional gp120/gp41 trimers, thereby blunting the ability of particles to elicit neutralizing antibodies. Here, we sought to better understand the nature of junk Env with a view to devising strategies for its removal. Initial studies revealed that native trimers were surprisingly stable in the face of harsh conditions, suggesting that junk Env is unlikely to arise by trimer dissociation or gp120 shedding. Furthermore, the limited gp120 shedding that occurs immediately after synthesis of primary HIV-1 isolate Envs is not caused by aberrant cleavage at the tandem gp120/gp41 cleavage sites, which were found to cleave in a codependent manner. A major VLP contaminant was found to consist of an early, monomeric form of gp160 that is glycosylated in the endoplasmic reticulum (gp160ER) and then bypasses protein maturation and traffics directly into particles. gp160ER was found to bind two copies of monoclonal antibody (MAb) 2G12, consistent with its exclusively high-mannose glycan profile. These findings prompted us to evaluate enzyme digests as a way to remove aberrant Env. Remarkably, sequential glycosidase-protease digests led to a complete or near-complete removal of junk Env from many viral strains, leaving trimers and viral infectivity largely intact. "Trimer VLPs" may be useful neutralizing antibody immunogens.

Indexed as

Antibodies, MonoclonalBinding SitesBroadly Neutralizing AntibodiesCell LineEndoplasmic Reticulumenv Gene Products, Human Immunodeficiency VirusGlycoside HydrolasesGlycosylationHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV Envelope Protein gp160HIV Envelope Protein gp41HumansPeptide HydrolasesProtein Binding2G12 monoclonal antibodyAntibodies, MonoclonalBroadly Neutralizing Antibodiesenv Gene Products, Human Immunodeficiency VirusGlycoside HydrolasesHIV AntibodiesHIV Envelope Protein gp120HIV Envelope Protein gp160HIV Envelope Protein gp41Peptide Hydrolases

Identifiers

PMID21471242
PMCPMC3126298
OpenAlexW2165390070

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.