Evidence map›Paper›PMID 17092531›Full record

ArticleVirology2007

Specific amino acids in the N-terminus of the gp41 ectodomain contribute to the stabilization of a soluble, cleaved gp140 envelope glycoprotein from human immunodeficiency virus type 1.

Antu K Dey, Kathryn B David, Per J Klasse, John P Moore

Open access · greenAbstract read
In one paragraph

Article in Virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

29 citing papers in PubMed, 48 citations in OpenAlex.

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  14. Stable, uncleaved HIV-1 envelope glycoprotein gp140 forms a tightly folded trimer with a native-like structure.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  15. Article
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  17. HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120.Proceedings of the National Academy of Sciences of the United States of America · 2012
    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

4 authors at 1 institution in 1 country.

Antu K DeyDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Room W-805, New York, NY 10021, USA.
Kathryn B David
Per J Klasse
John P Moore
Cornell University · US

Funding

NEUTRALIZATION OF PRIMARY HIV1 VIRUSESR37AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 1998 to 2017
$7.0M
Neutralization of Primate Immunodeficiency VirusesR01AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI JOHN P MOORE · 1994 to 2026
$4.3M
MODIFIED ENVELOPE GLYCOPROTEINS FOR HIV1 VACCINER01AI045463 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 1999 to 2010
$4.2M
HIV VACCINE DESIGN AND DEVELOPMENT TEAMS (HVDDT)-266030030N01AI030030 · NIAID · PROGENICS PHARMACEUTICALS, INC · PI MADDON, PAUL J · 2003 to 2003
–
NIAID NIH HHS AI 36082NIAID NIH HHS AI 45463NIAID NIH HHS N01 AI030030NIAID NIH HHS R01 AI036082NIAID NIH HHS R01 AI045463NIAID NIH HHS R37 AI036082
6 · The paper itself

Abstract

The HIV-1 envelope glycoprotein is expressed on the viral membrane as a trimeric complex, formed by three gp120 surface glycoproteins non-covalently associated with three membrane-anchored gp41 subunits. The labile nature of the association between gp120 and gp41 hinders the expression of soluble, fully cleaved, trimeric gp140 proteins for structural and immunization studies. Disruption of the primary cleavage site within gp160 allows the production of stable gp140 trimers, but cleavage-defective trimers are antigenically dissimilar from their cleaved counterparts. Soluble, stabilized, proteolytically cleaved, trimeric gp140 proteins can be generated by engineering an intermolecular disulfide bond between gp120 and gp41 (SOS), combined with a single residue change, I559P, within gp41 (SOSIP). We have found that SOSIP gp140 proteins based on the subtype A HIV-1 strain KNH1144 form particularly homogenous trimers compared to a prototypic strain (JR-FL, subtype B). We now show that the determinants of this enhanced stability are located in the N-terminal region of KNH11144 gp41 and that, when substituted into heterologous Env sequences (e.g., JR-FL and Ba-L) they have a similarly beneficial effect on trimer stability. The stabilized trimers retain the epitopes for several neutralizing antibodies (b12, 2G12, 2F5 and 4E10) and the CD4-IgG2 molecule, suggesting that the overall antigenic structure of the gp140 protein has not been adversely impaired by the trimer-stabilizing substitutions. The ability to increase the stability of gp140 trimers might be useful for neutralizing antibody-based vaccine strategies based on the use of this type of immunogen.

Indexed as

Amino Acid SequenceAntibodies, MonoclonalCD4 ImmunoadhesinsCell Lineenv Gene Products, Human Immunodeficiency VirusEpitopesGene Products, envHIV-1HIV AntibodiesHIV Envelope Protein gp41HumansMolecular Sequence DataNeutralization TestsProtein Structure, TertiarySequence AlignmentSolubilityAntibodies, MonoclonalCD4 Immunoadhesinsenv Gene Products, Human Immunodeficiency VirusEpitopesGene Products, envgp140 envelope protein, Human immunodeficiency virus 1HIV AntibodiesHIV Envelope Protein gp41

Identifiers

PMID17092531
PMCPMC1857345
OpenAlexW1976584377

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.