Evidence map›Paper›PMID 31658290›Full record

ArticlePLoS pathogens2019

Cooperativity between the 3' untranslated region microRNA binding sites is critical for the virulence of eastern equine encephalitis virus.

Derek W Trobaugh, Chengqun Sun, Nishank Bhalla, Christina L Gardner, Matthew D Dunn, William B Klimstra

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.3field-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

19 citing papers in PubMed, 28 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Derek W TrobaughCenter for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America.ORCID 0000-0002-7312-0260
Chengqun SunCenter for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America.
Nishank BhallaCenter for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America.
Christina L GardnerCenter for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America.ORCID 0000-0002-3475-8966
Matthew D DunnCenter for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America.
William B KlimstraCenter for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America.ORCID 0000-0003-4506-7842
University of Pittsburgh · US

Funding

Molecular Mechanisms of Eastern Equine Encephalitis Virus PathogenesisR01AI095436 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLIMSTRA, WILLIAM B · 2012 to 2022
$4.5M
T cell responses during eastern equine encephalitis virus infectionR21AI132909 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TROBAUGH, DEREK W. · 2017 to 2018
$426k
Characterization of microRNA binding sites in the eastern equine encephalitis virus 3'NTRR21AI111115 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLIMSTRA, WILLIAM B · 2015 to 2016
$412k
NIAID NIH HHS R01 AI095436NIAID NIH HHS R21 AI111115NIAID NIH HHS R21 AI132909
6 · The paper itself

Abstract

Eastern equine encephalitis virus (EEEV), a mosquito-borne RNA virus, is one of the most acutely virulent viruses endemic to the Americas, causing between 30% and 70% mortality in symptomatic human cases. A major factor in the virulence of EEEV is the presence of four binding sites for the hematopoietic cell-specific microRNA, miR-142-3p, in the 3' untranslated region (3' UTR) of the virus. Three of the sites are "canonical" with all 7 seed sequence residues complimentary to miR-142-3p while one is "non-canonical" and has a seed sequence mismatch. Interaction of the EEEV genome with miR-142-3p limits virus replication in myeloid cells and suppresses the systemic innate immune response, greatly exacerbating EEEV neurovirulence. The presence of the miRNA binding sequences is also required for efficient EEEV replication in mosquitoes and, therefore, essential for transmission of the virus. In the current studies, we have examined the role of each binding site by point mutagenesis of the seed sequences in all combinations of sites followed by infection of mammalian myeloid cells, mosquito cells and mice. The resulting data indicate that both canonical and non-canonical sites contribute to cell infection and animal virulence, however, surprisingly, all sites are rapidly deleted from EEEV genomes shortly after infection of myeloid cells or mice. Finally, we show that the virulence of a related encephalitis virus, western equine encephalitis virus, is also dependent upon miR-142-3p binding sites.

Indexed as

3' Untranslated RegionsAedesAnimalsBinding SitesCell LineCricetinaeEncephalitis Virus, Eastern EquineEncephalitis Virus, Western EquineEncephalomyelitis, EquineFemaleImmunity, InnateL CellsMiceMice, Inbred C3HMice, Inbred C57BLMicroRNAs3' Untranslated RegionsMicroRNAsMirn142 microRNA, mouse

Identifiers

PMID31658290
PMCPMC6936876
OpenAlexW2982631953

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.