Evidence map›Paper›PMID 25395053›Full record

ArticleScientific reports2014

Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops.

Carlos G Moscoso, Li Xing, Jinwen Hui, Jeffrey Hu, Mohammad Baikoghli Kalkhoran, Onur M Yenigun, Yide Sun, Lassi Paavolainen, Loïc Martin, Anders Vahlne and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 28% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016
    Pooled it
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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

14 authors at 4 institutions in 4 countries.

Carlos G MoscosoDepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616.
Li XingDepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616.
Jinwen HuiDepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616.
Jeffrey HuDepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616.
Mohammad Baikoghli KalkhoranDepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616.
Onur M YenigunDepartment of Molecular and Cellular Biology, University of California, Davis, CA 95616.
Yide SunNovartis Vaccines and Diagnostics Inc., 45 Sydney Street, Cambridge, MA 02139.
Lassi PaavolainenDepartment of Biological and Environmental Science/Nanoscience Center, University of Jyväskylä, FI-40351 Jyväskylä, Finland.
Loïc MartinCommissariat à l'énergie atomique et aux énergies alternatives, Institut de Biologie et Technologies de Saclay, Service d'Ingénierie Moléculaire des Protéines, Gif-sur-Yvette F-91191, France.
Anders VahlneKarolinska Institutet, Structural Virology, Clinical Microbiology/University Hospital, 171 77 Stockholm, Sweden.
Carlo ZambonelliNovartis Vaccines and Diagnostics Inc., 45 Sydney Street, Cambridge, MA 02139.
Susan W BarnettNovartis Vaccines and Diagnostics Inc., 45 Sydney Street, Cambridge, MA 02139.
Indresh K SrivastavaNovartis Vaccines and Diagnostics Inc., 45 Sydney Street, Cambridge, MA 02139.
R Holland Cheng1] Department of Molecular and Cellular Biology, University of California, Davis, CA 95616 [2] Karolinska Institutet, Structural Virology, Clinical Microbiology/University Hospital, 171 77 Stockholm, Sweden.
University of California, Davis · USKarolinska Institutet · SECommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRUniversity of Jyväskylä · FI

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Laura Marcu · 2002 to 2026
$84.9M
NCI NIH HHS P30 CA093373
6 · The paper itself

Abstract

Hypervariable loops of HIV-1 Env protein gp120 are speculated to play roles in the conformational transition of Env to the receptor binding-induced metastable state. Structural analysis of full-length Env-based immunogens, containing the entire V2 loop, displayed tighter association between gp120 subunits, resulting in a smaller trimeric diameter than constructs lacking V2. A prominent basal quaternary location of V2 and V3' that challenges previous reports would facilitate gp41-independent gp120-gp120 interactions and suggests a quaternary mechanism of epitope occlusion facilitated by hypervariable loops. Deletion of V2 resulted in dramatic exposure of basal, membrane-proximal gp41 epitopes, consistent with its predicted basal location. The structural features of HIV-1 Env characterized here provide grounds for a paradigm shift in loop exposure and epitope occlusion, while providing substantive rationale for epitope display required for elicitation of broadly neutralizing antibodies, as well as substantiating previous pertinent literature disregarded in recent reports.

Indexed as

Protein MultimerizationCD4 Antigensenv Gene Products, Human Immunodeficiency VirusEpitopesHIV Envelope Protein gp120HIV Envelope Protein gp41HumansModels, MolecularPeptide FragmentsProtein BindingProtein ConformationProtein Interaction Domains and MotifsSequence DeletionCD4 Antigensenv Gene Products, Human Immunodeficiency VirusEpitopesHIV Envelope Protein gp120HIV Envelope Protein gp41Peptide Fragments

Identifiers

PMID25395053
PMCPMC4231788
OpenAlexW1985663620

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.