Evidence map›Paper›PMID 12502809›Full record

ArticleJournal of virology2003

Identification of gp120 binding sites on CXCR4 by using CD4-independent human immunodeficiency virus type 2 Env proteins.

George Lin, Frédéric Baribaud, Josephine Romano, Robert W Doms, James A Hoxie

Abstract read
In one paragraph

Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
0.9field-weighted citation impact, top 31% 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

27 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Endogenous Peptide Inhibitors of HIV Entry.Advances in experimental medicine and biology · 2022
    Article
  6. Article
  7. Molecular Mechanism of HIV-1 Entry.Trends in microbiology · 2019
    Review
  8. Effects of HIV-1 gp120 and TAT-derived microvesicles on endothelial cell function.Journal of applied physiology (Bethesda, Md. : 1985) · 2019
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

5 authors at 2 institutions in 1 country.

George LinHematology-Oncology Division, Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Frédéric Baribaud
Josephine Romano
Robert W Doms
James A Hoxie
Palmetto Hematology Oncology · USUniversity of Pennsylvania · US

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6M
EVALUATION OF CD4 INDEPENDENT HIV AND SIV ENV PROTEINSR01AI045378 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HOXIE, JAMES A · 1999 to 2003
$1.8M
NIAID NIH HHS P30 AI045008NIAID NIH HHS P30 AI45008NIAID NIH HHS R01 AI045378NIAID NIH HHS R01 AI45378NIMHD NIH HHS L60 MD003100PHS HHS R01 35383PHS HHS R01 40880
6 · The paper itself

Abstract

Human immunodeficiency virus (HIV) and simian (SIV) immunodeficiency virus entry is mediated by binding of the viral envelope glycoprotein (Env) to CD4 and chemokine receptors, CCR5 and/or CXCR4. CD4 induces extensive conformational changes that expose and/or induce formation of a chemokine receptor binding site on gp120. CD4-independent Env's of HIV type 1 (HIV-1), HIV-2, and SIV have been identified that exhibit exposed chemokine receptor binding sites and can bind directly to CCR5 or CXCR4 in the absence of CD4. While many studies have examined determinants for gp120-CCR5 binding, analysis of gp120-CXCR4 binding has been hindered by the apparently lower affinity of this interaction for X4-tropic HIV-1 isolates. We show here that gp120 proteins from two CD4-independent HIV-2 Env's, VCP and ROD/B, bind directly to CXCR4 with an apparently high affinity. By use of CXCR4 N-terminal deletion constructs, CXCR4-CXCR2 chimeras, and human-rat CXCR4 chimeras, binding determinants were shown to reside in the amino (N) terminus, extracellular loop 2 (ECL2), and ECL3. Alanine-scanning mutagenesis of charged residues, tyrosines, and phenylalanines in extracellular CXCR4 domains implicated multiple amino acids in the N terminus (E14/E15, D20, Y21, and D22), ECL2 (D187, R188, F189, Y190, and D193), and ECL3 (D262, E268, E277, and E282) in binding, although minor differences were noted between VCP and ROD/B. However, mutations in CXCR4 that markedly reduced binding did not necessarily hinder cell-cell fusion by VCP or ROD/B, especially in the presence of CD4. These gp120 proteins will be useful in dissecting determinants for CXCR4 binding and Env triggering and in evaluating pharmacologic inhibitors of the gp120-CXCR4 interaction.

Indexed as

AnimalsBinding SitesCD4 AntigensHIV-2HIV Envelope Protein gp120HumansMutationProtein BindingRatsReceptors, CXCR4Recombinant Fusion ProteinsSequence DeletionCD4 AntigensHIV Envelope Protein gp120Receptors, CXCR4Recombinant Fusion Proteins

Identifiers

PMID12502809
PMCPMC140809
OpenAlexW2135626219

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.