Evidence map›Paper›PMID 15650179›Full record

ArticleJournal of virology2005

Elimination of retroviral infectivity by N-ethylmaleimide with preservation of functional envelope glycoproteins.

David R Morcock, James A Thomas, Tracy D Gagliardi, Robert J Gorelick, J David Roser, Elena N Chertova, Julian W Bess, David E Ott, Quentin J Sattentau, Ines Frank and 4 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
0.9field-weighted citation impact, top 30% 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

21 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Antigenic composition of single nano-sized extracellular blood vesicles.Nanomedicine : nanotechnology, biology, and medicine · 2015
    Article
  8. Nucleocapsid Protein: A Desirable Target for Future Therapies Against HIV-1.Current topics in microbiology and immunology · 2015
    Review
  9. HIV-1 gag: an emerging target for antiretroviral therapy.Current topics in microbiology and immunology · 2015
    Review
  10. Review
  11. Article
  12. Simian immunodeficiency virus interactions with macaque dendritic cells.Advances in experimental medicine and biology · 2013
    Review
  13. Article
  14. HIV type 1 Gag as a target for antiviral therapy.AIDS research and human retroviruses · 2012
    Review
  15. Article
  16. Article
  17. Review
  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

14 authors at 4 institutions in 2 countries.

David R MorcockAIDS Vaccine Program, SAIC Frederick, NCI-Frederick, Building 535, 5th Floor, PO Box B, Frederick, MD 21702, USA.
James A Thomas
Tracy D Gagliardi
Robert J Gorelick
J David Roser
Elena N Chertova
Julian W Bess
David E Ott
Quentin J Sattentau
Ines Frank
Melissa Pope
Jeffrey D Lifson
Louis E Henderson
Bruce J Crise
National Cancer Institute · USScience Applications International Corporation (United States) · USPopulation Council · USUniversity of Oxford · GB

Funding

The Mucosal Dendritic Cell T Milieu and SIV SpreadR01AI040877 · NIAID · ROCKEFELLER UNIVERSITY · PI DERBY, NINA R. · 1997 to 2016
$6.9M
Modulating mucosal DCs and T cells to limit SIV spreadR37AI040877 · NIAID · POPULATION COUNCIL · PI ROBBIANI, MELISSA J · 2007 to 2013
$6.4M
PHARMACOKINETICS/TOXICOLOGY OF CARRAGEENAN MICROBICIDESP01HD041752 · NICHD · POPULATION COUNCIL · PI PHILLIPS, DAVID · 2001 to 2004
$6.0M
HIV 1 fusion/entry inhibitors in tissue modelsP01AI052048 · NIAID · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI MOORE, JOHN P · 2001 to 2004
$5.2M
NCI NIH HHS N01 CO012400NCI NIH HHS N01-CO-12400NIAID NIH HHS AI40877NIAID NIH HHS AI52048NIAID NIH HHS P01 AI052048NIAID NIH HHS R01 AI040877NIAID NIH HHS R37 AI040877NICHD NIH HHS HD41752NICHD NIH HHS P01 HD041752
6 · The paper itself

Abstract

The zinc finger motifs in retroviral nucleocapsid (NC) proteins are essential for viral replication. Disruption of these Cys-X2-Cys-X4-His-X4-Cys zinc-binding structures eliminates infectivity. To determine if N-ethylmaleimide (NEM) can inactivate human immunodeficiency virus type 1 (HIV-1) or simian immunodeficiency virus (SIV) preparations by alkylating cysteines of NC zinc fingers, we treated infectious virus with NEM and evaluated inactivation of infectivity in cell-based assays. Inactivation was rapid and proportional to the NEM concentration. NEM treatment of HIV-1 or SIV resulted in extensive covalent modification of NC and other internal virion proteins. In contrast, viral envelope glycoproteins, in which the cysteines are disulfide bonded, remained intact and functional, as assayed by high-performance liquid chromatography, fusion-from-without analyses, and dendritic cell capture. Quantitative PCR assays for reverse transcription intermediates showed that NEM and 2,2'-dipyridyl disulfide (aldrithiol-2), a reagent which inactivates retroviruses through oxidation of cysteines in internal virion proteins such as NC, blocked HIV-1 reverse transcription prior to the formation of minus-strand strong-stop products. However, the reverse transcriptase from NEM-treated virions remained active in exogenous template assays, consistent with a role for NC in reverse transcription. Since disruption of NC zinc finger structures by NEM blocks early postentry steps in the retroviral infection cycle, virus preparations with modified NC proteins may be useful as vaccine immunogens and probes of the role of NC in viral replication.

Indexed as

Cell LineDendritic CellsEthylmaleimideGene Products, envHeLa CellsHIV-1HumansKineticsNucleocapsidSimian Immunodeficiency VirusZinc FingersEthylmaleimideGene Products, env

Identifiers

PMID15650179
PMCPMC544125
OpenAlexW2129061204

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.