Evidence map›Paper›PMID 25927990›Full record

ArticlePloS one2015

The ubiquitin proteasome system plays a role in venezuelan equine encephalitis virus infection.

Moushimi Amaya, Forrest Keck, Michael Lindquist, Kelsey Voss, Lauren Scavone, Kylene Kehn-Hall, Brian Roberts, Charles Bailey, Connie Schmaljohn, Aarthi Narayanan

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.0field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Eastern Equine Encephalitis Virus: A Scoping Review of the Global Evidence.Vector borne and zoonotic diseases (Larchmont, N.Y.) · 2021
    Article
  12. Review
  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

10 authors at 3 institutions in 1 country.

Moushimi AmayaNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Forrest KeckNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Michael LindquistUnited States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
Kelsey VossNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Lauren ScavoneNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Kylene Kehn-HallNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Brian RobertsLeidos Health Life Sciences, Frederick, Maryland, United States of America.
Charles BaileyNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
Connie SchmaljohnUnited States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
Aarthi NarayananNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, United States of America.
George Mason University · USUnited States Army Medical Research Institute of Infectious Diseases · USLeidos (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS) to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV) belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-toxic concentrations Bortezomib, a FDA-approved inhibitor of the proteasome, proved to be a potent inhibitor of VEEV multiplication in the human astrocytoma cell line U87MG. Bortezomib inhibited the virulent Trinidad donkey (TrD) strain and the attenuated TC-83 strain of VEEV. Additional studies with virulent strains of Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV) demonstrated that Bortezomib is a broad spectrum inhibitor of the New World alphaviruses. Time-of-addition assays showed that Bortezomib was an effective inhibitor of viral multiplication even when the drug was introduced many hours post exposure to the virus. Mass spectrometry analyses indicated that the VEEV capsid protein is ubiquitinated in infected cells, which was validated by confocal microscopy and immunoprecipitation assays. Subsequent studies revealed that capsid is ubiquitinated on K48 during early stages of infection which was affected by Bortezomib treatment. This study will aid future investigations in identifying host proteins as potential broad spectrum therapeutic targets for treating alphavirus infections.

Indexed as

AnimalsBlotting, WesternBortezomibCell SurvivalEncephalitis Virus, Venezuelan EquineEncephalomyelitis, Venezuelan EquineGuinea PigsImmunoprecipitationIn Situ Hybridization, FluorescenceProteasome Endopeptidase ComplexTandem Mass SpectrometryUbiquitinBortezomibProteasome Endopeptidase ComplexUbiquitin

Identifiers

PMID25927990
PMCPMC4415917
OpenAlexW2016433543

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.