Evidence map›Paper›PMID 27852852›Full record

ArticleJournal of virology2017

Ablation of Programmed -1 Ribosomal Frameshifting in Venezuelan Equine Encephalitis Virus Results in Attenuated Neuropathogenicity.

Joseph A Kendra, Cynthia de la Fuente, Ashwini Brahms, Caitlin Woodson, Todd M Bell, Bin Chen, Yousuf A Khan, Jonathan L Jacobs, Kylene Kehn-Hall, Jonathan D Dinman

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 55 citations in OpenAlex.

  1. Review
  2. Integrated phenotypic screening and chemical proteomics identifies ETF1 ligands that modulate viral translation and replication.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  13. Innate immune evasion by alphaviruses.Frontiers in immunology · 2022
    Review
  14. Review
  15. Shiftless inhibits flavivirus replication in vitro and is neuroprotective in a mouse model of Zika virus pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  16. Review
  17. Article
  18. Alphavirus Virulence Determinants.Pathogens (Basel, Switzerland) · 2021
    Review
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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.

Joseph A KendraDepartment of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA.
Cynthia de la FuenteNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA.
Ashwini BrahmsNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA.
Caitlin WoodsonNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA.
Todd M BellNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA.
Bin ChenDepartment of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA.
Yousuf A KhanDepartment of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA.
Jonathan L JacobsMRIGlobal, Global Health Security, Rockville, Maryland, USA.
Kylene Kehn-HallNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA kkehnhal@gmu.edu dinman@umd.edu.
Jonathan D DinmanDepartment of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA kkehnhal@gmu.edu dinman@umd.edu.ORCID http://orcid.org/0000-0002-2402-9698
George Mason University · USUniversity of Maryland, College Park · USMRIGlobal · US

Funding

Mechanisms of Virus Replication and Gene ExpressionT32AI051967 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI SIMON, ANNE ELIZABETH · 2002 to 2013
$1.8M
Graduate Training in VirologyT32AI125186 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI SIMON, ANNE ELIZABETH · 2016 to 2020
$1.3M
NIAID NIH HHS T32 AI051967NIAID NIH HHS T32 AI125186
6 · The paper itself

Abstract

The alphaviruses Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV) are arthropod-borne positive-strand RNA viruses that are capable of causing acute and fatal encephalitis in many mammals, including humans. VEEV was weaponized during the Cold War and is recognized as a select agent. Currently, there are no FDA-approved vaccines or therapeutics for these viruses. The spread of VEEV and other members of this family due to climate change-mediated vector range expansion underscores the need for research aimed at developing medical countermeasures. These viruses utilize programmed -1 ribosomal frameshifting (-1 PRF) to synthesize the viral trans-frame (TF) protein, which has previously been shown to be important for neuropathogenesis in the related Sindbis virus. Here, the alphavirus -1 PRF signals were characterized, revealing novel -1 PRF stimulatory structures. -1 PRF attenuation mildly affected the kinetics of VEEV accumulation in cultured cells but strongly inhibited its pathogenesis in an aerosol infection mouse model. Importantly, the decreased viral titers in the brains of mice infected with the mutant virus suggest that the alphavirus TF protein is important for passage through the blood-brain barrier and/or for neuroinvasiveness. These findings suggest a novel approach to the development of safe and effective live attenuated vaccines directed against VEEV and perhaps other closely related -1 PRF-utilizing viruses. IMPORTANCE: Venezuelan equine encephalitis virus (VEEV) is a select agent that has been weaponized. This arthropod-borne positive-strand RNA virus causes acute and fatal encephalitis in many mammals, including humans. There is no vaccine or other approved therapeutic. VEEV and related alphaviruses utilize programmed -1 ribosomal frameshifting (-1 PRF) to synthesize the viral trans-frame (TF) protein, which is important for neuropathogenesis. -1 PRF attenuation strongly inhibited VEEV pathogenesis in mice, and viral replication analyses suggest that the TF protein is critical for neurological disease. These findings suggest a new approach to the development of safe and effective live attenuated vaccines directed against VEEV and other related viruses.

Indexed as

Frameshifting, RibosomalAnimalsCell LineEncephalitis Virus, Venezuelan EquineEncephalomyelitis, Venezuelan EquineFemaleGenome, ViralHorsesHumansNucleic Acid ConformationOpen Reading FramesRNA, MessengerRNA, ViralVirus ReplicationRNA, MessengerRNA, Viralalphavirusneuropathologyribosomal frameshiftingvaccinevirus

Identifiers

PMID27852852
PMCPMC5244343
OpenAlexW2553775999

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.