Evidence map›Paper›PMID 22069466›Full record

ArticlePloS one2011

An inducible cell-cell fusion system with integrated ability to measure the efficiency and specificity of HIV-1 entry inhibitors.

Alon Herschhorn, Andres Finzi, David M Jones, Joel R Courter, Akihiro Sugawara, Amos B Smith, Joseph G Sodroski

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
0.1field-weighted citation impact, top 56% 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

30 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Alternative substitutions of N332 in HIV-1bioRxiv : the preprint server for biology · 2023
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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 3 institutions in 1 country.

Alon HerschhornDepartment of Immunology Cancer and AIDS, Dana-Farber Cancer Institute and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
Andres Finzi
David M Jones
Joel R Courter
Akihiro Sugawara
Amos B Smith
Joseph G Sodroski
University of Pennsylvania · USDana-Farber Cancer Institute · USHarvard University · US

Funding

Viral Sequencing CoreU19AI067854 · NIAID · DUKE UNIVERSITY · PI CRUMP, JOHN ANDREW · 2006 to 2011
$290.5M
The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ROBERT A. PARKER · 2004 to 2026
$94.4M
Understanding Envelope Function in HIV-1 Infection: The Design, Synthesis and Validation of Small Molecule HIV-1 Env InhibitorsP01GM056550 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI ABRAMS, CAMERON F · 1997 to 2018
$31.2M
Viral and Host Determinants of HIV-1 TransmissionU01AI067854 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F · 2005 to 2005
$14.9M
HIV-1 ENVELOPE GLYCOPROTEINSR37AI024755 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1996 to 2015
$11.6M
ROLE OF THE HTLV-III ENVELOPE GLYCOPROTEIN IN VIRUSR01AI024755 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1987 to 1995
–
NIAID NIH HHS AI24755NIAID NIH HHS AI60354NIAID NIH HHS AI67854NIAID NIH HHS P30 AI060354NIAID NIH HHS R37 AI024755NIAID NIH HHS U01 AI067854NIAID NIH HHS U19 AI067854NIGMS NIH HHS GM56550NIGMS NIH HHS P01 GM056550
6 · The paper itself

Abstract

HIV-1 envelope glycoproteins (Envs) mediate virus entry by fusing the viral and target cell membranes, a multi-step process that represents an attractive target for inhibition. Entry inhibitors with broad-range activity against diverse isolates of HIV-1 may be extremely useful as lead compounds for the development of therapies or prophylactic microbicides. To facilitate the identification of such inhibitors, we have constructed a cell-cell fusion system capable of simultaneously monitoring inhibition efficiency and specificity. In this system, effector cells stably express a tetracycline-controlled transactivator (tTA) that enables tightly inducible expression of both HIV-1 Env and the Renilla luciferase (R-Luc) reporter protein. Target cells express the HIV-1 receptors, CD4 and CCR5, and carry the firefly luciferase (F-Luc) reporter gene under the control of a tTA-responsive promoter. Thus, Env-mediated fusion of these two cell types allows the tTA to diffuse to the target cell and activate the expression of the F-Luc protein. The efficiency with which an inhibitor blocks cell-cell fusion is measured by a decrease in the F-Luc activity, while the specificity of the inhibitor is evaluated by its effect on the R-Luc activity. The system exhibited a high dynamic range and high Z'-factor values. The assay was validated with a reference panel of inhibitors that target different steps in HIV-1 entry, yielding inhibitory concentrations comparable to published virus inhibition data. Our system is suitable for large-scale screening of chemical libraries and can also be used for detailed characterization of inhibitory and cytotoxic properties of known entry inhibitors.

Indexed as

CCR5 Receptor AntagonistsCD4 AntigensCell FusionFlow CytometryHeLa CellsHIV-1HIV Envelope Protein gp120HIV Fusion InhibitorsHIV InfectionsHumansImmunoprecipitationLuciferases, RenillaMembrane FusionReceptors, CCR5Receptors, HIVVirus InternalizationCCR5 Receptor AntagonistsCD4 AntigensHIV Envelope Protein gp120HIV Fusion InhibitorsLuciferases, RenillaReceptors, CCR5Receptors, HIV

Identifiers

PMID22069466
PMCPMC3206054
OpenAlexW2080108288

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.