Evidence map›Paper›PMID 10954535›Full record

ArticleJournal of virology2000

Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120.

C A Derdeyn, J M Decker, J N Sfakianos, X Wu, W A O'Brien, L Ratner, J C Kappes, G M Shaw, E Hunter

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 480 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
480citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 8% 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

480 citing papers in PubMed, 2 syntheses or guidelines pooled it, 747 citations in OpenAlex.

  1. Pooled it
  2. 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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420 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

9 authors at 5 institutions in 2 countries.

C A DerdeynDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
J M Decker
J N Sfakianos
X Wu
W A O'Brien
L Ratner
J C Kappes
G M Shaw
E Hunter
Czech Academy of Sciences, Institute of Microbiology · CZHoward Hughes Medical Institute · USUniversity of Alabama at Birmingham · USThe University of Texas Medical Branch at Galveston · USWashington University in St. Louis · US

Funding

PATHOGENESIS OF HUMAN IMMUNODEFICIENCY VIRUS INFECTIONR01AI024745 · NIAID · WASHINGTON UNIVERSITY · PI RATNER, LEE · 1987 to 2007
$1.5M
NIAID NIH HHS R01 AI024745NIAID NIH HHS R37AI24745PHS HHS P30-A1-27767PHS HHS R37A133319
6 · The paper itself

Abstract

T-20 is a synthetic peptide that potently inhibits replication of human immunodeficiency virus type 1 by interfering with the transition of the transmembrane protein, gp41, to a fusion active state following interactions of the surface glycoprotein, gp120, with CD4 and coreceptor molecules displayed on the target cell surface. Although T-20 is postulated to interact with an N-terminal heptad repeat within gp41 in a trans-dominant manner, we show here that sensitivity to T-20 is strongly influenced by coreceptor specificity. When 14 T-20-naive primary isolates were analyzed for sensitivity to T-20, the mean 50% inhibitory concentration (IC(50)) for isolates that utilize CCR5 for entry (R5 viruses) was 0.8 log(10) higher than the mean IC(50) for CXCR4 (X4) isolates (P = 0. 0055). Using NL4.3-based envelope chimeras that contain combinations of envelope sequences derived from R5 and X4 viruses, we found that determinants of coreceptor specificity contained within the gp120 V3 loop modulate this sensitivity to T-20. The IC(50) for all chimeric envelope viruses containing R5 V3 sequences was 0.6 to 0.8 log(10) higher than that for viruses containing X4 V3 sequences. In addition, we confirmed that the N-terminal heptad repeat of gp41 determines the baseline sensitivity to T-20 and that the IC(50) for viruses containing GIV at amino acid residues 36 to 38 was 1.0 log(10) lower than the IC(50) for viruses containing a G-to-D substitution. The results of this study show that gp120-coreceptor interactions and the gp41 N-terminal heptad repeat independently contribute to sensitivity to T-20. These results have important implications for the therapeutic uses of T-20 as well as for unraveling the complex mechanisms of virus fusion and entry.

Indexed as

Anti-HIV AgentsCD4 AntigensCell LineEnfuvirtideHeLa CellsHIV-1HIV Envelope Protein gp120HIV Envelope Protein gp41HumansPeptide FragmentsReceptors, CCR5Receptors, CXCR4Receptors, HIVVirus ReplicationAnti-HIV AgentsCD4 AntigensEnfuvirtideHIV Envelope Protein gp120HIV Envelope Protein gp41Peptide FragmentsReceptors, CCR5Receptors, CXCR4Receptors, HIV

Identifiers

PMID10954535
PMCPMC116346
OpenAlexW2153747683

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.