Evidence map›Paper›PMID 20335257›Full record

ArticleJournal of virology2010

Role of complex carbohydrates in human immunodeficiency virus type 1 infection and resistance to antibody neutralization.

James M Binley, Yih-En Andrew Ban, Emma T Crooks, Dirk Eggink, Keiko Osawa, William R Schief, Rogier W Sanders

Abstract read
In one paragraph

Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

92 citing papers in PubMed, 140 citations in OpenAlex.

  1. Review
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  8. Review
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  11. Synthetic Carbohydrate Chemistry and Translational Medicine.The Journal of organic chemistry · 2020
    Article
  12. Article
  13. Article
  14. Article
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  19. Signal peptide of HIV envelope protein impacts glycosylation and antigenicity of gp120.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  20. Article

32 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

7 authors at 5 institutions in 2 countries.

James M BinleyTorrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA. jbinley@tpims.org
Yih-En Andrew Ban
Emma T Crooks
Dirk Eggink
Keiko Osawa
William R Schief
Rogier W Sanders
General Atomics (United States) · USUniversity of Washington · USAcademic Medical Center · NLTorrey Pines Institute For Molecular Studies · USUniversity of Amsterdam · NL

Funding

Pure and Authentic HIV-1 Env ImmunogensR01AI093278 · NIAID · TORREY PINES INST FOR MOLECULAR STUDIES · PI BINLEY, JAMES M · 2011 to 2024
$11.6M
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 SubunitsR21AI084714 · NIAID · TORREY PINES INST FOR MOLECULAR STUDIES · PI BINLEY, JAMES M · 2009 to 2010
$493k
NIAID NIH HHS R01 AI058763NIAID NIH HHS R01 AI093278NIAID NIH HHS R01 AI58763NIAID NIH HHS R21 AI084714
6 · The paper itself

Abstract

Complex N-glycans flank the receptor binding sites of the outer domain of HIV-1 gp120, ostensibly forming a protective "fence" against antibodies. Here, we investigated the effects of rebuilding this fence with smaller glycoforms by expressing HIV-1 pseudovirions from a primary isolate in a human cell line lacking N-acetylglucosamine transferase I (GnTI), the enzyme that initiates the conversion of oligomannose N-glycans into complex N-glycans. Thus, complex glycans, including those that surround the receptor binding sites, are replaced by fully trimmed oligomannose stumps. Conversely, the untrimmed oligomannoses of the silent domain of gp120 are likely to remain unchanged. For comparison, we produced a mutant virus lacking a complex N-glycan of the V3 loop (N301Q). Both variants exhibited increased sensitivities to V3 loop-specific monoclonal antibodies (MAbs) and soluble CD4. The N301Q virus was also sensitive to "nonneutralizing" MAbs targeting the primary and secondary receptor binding sites. Endoglycosidase H treatment resulted in the removal of outer domain glycans from the GnTI- but not the parent Env trimers, and this was associated with a rapid and complete loss in infectivity. Nevertheless, the glycan-depleted trimers could still bind to soluble receptor and coreceptor analogs, suggesting a block in post-receptor binding conformational changes necessary for fusion. Collectively, our data show that the antennae of complex N-glycans serve to protect the V3 loop and CD4 binding site, while N-glycan stems regulate native trimer conformation, such that their removal can lead to global changes in neutralization sensitivity and, in extreme cases, an inability to complete the conformational rearrangements necessary for infection.

Indexed as

Drug ResistanceAntibodies, ViralBinding SitesCD4 AntigensCell LineHIV-1HIV Envelope Protein gp120HIV InfectionsHumansN-AcetylglucosaminyltransferasesNeutralization TestsPolysaccharidesVirionAntibodies, ViralCD4 AntigensHIV Envelope Protein gp120N-AcetylglucosaminyltransferasesPolysaccharidesUDP-GlcNAc alpha-D-mannoside beta-1,2-N-acetylglucosaminyltransferase

Identifiers

PMID20335257
PMCPMC2876609
OpenAlexW2149132834

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.