Evidence map›Paper›PMID 31393953›Full record

ArticlePLoS pathogens2019

Identification of murine gammaherpesvirus 68 miRNA-mRNA hybrids reveals miRNA target conservation among gammaherpesviruses including host translation and protein modification machinery.

Whitney L Bullard, Mehmet Kara, Lauren A Gay, Sunantha Sethuraman, Yiping Wang, Shreya Nirmalan, Alim Esemenli, April Feswick, Brett A Hoffman, Rolf Renne and 1 more

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 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.0field-weighted citation impact, top 12% 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

23 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
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  7. Evaluation of immune sensor responses to a viral small noncoding RNA.Frontiers in cellular and infection microbiology · 2024
    Article
  8. Article
  9. Viral miRNA regulation of host gene expression.Seminars in cell & developmental biology · 2023
    Review
  10. Article
  11. Review
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  15. Article
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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

11 authors at 1 institution in 1 country.

Whitney L BullardDept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.
Mehmet KaraDept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.ORCID 0000-0002-9646-4584
Lauren A GayDept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.ORCID 0000-0001-5715-6717
Sunantha SethuramanDept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.
Yiping WangDept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.ORCID 0000-0002-3178-3752
Shreya NirmalanDept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.ORCID 0000-0002-1946-0168
Alim EsemenliDept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.
April FeswickDept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.ORCID 0000-0003-4221-2346
Brett A HoffmanDept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.
Rolf RenneDept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.ORCID 0000-0001-7391-8806
Scott A TibbettsDept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.ORCID 0000-0001-8889-1642
University of Florida Health · US

Funding

"Project 3" MHV68 IncRNA/miRNA interaction in latency and lympomagenesisP01CA214091 · NCI · UNIVERSITY OF FLORIDA · PI Scott A. Tibbetts · 2017 to 2026
$15.9M
Role of MHV68 miRNAs in latencyand pathogenesisR01AI108407 · NIAID · UNIVERSITY OF FLORIDA · PI TIBBETTS, SCOTT A. · 2015 to 2019
$2.0M
NCI NIH HHS P01 CA214091NIAID NIH HHS R01 AI108407
6 · The paper itself

Abstract

Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), establish lifelong latent infection in B cells and are associated with a variety of tumors. In addition to protein coding genes, these viruses encode numerous microRNAs (miRNAs) within their genomes. While putative host targets of EBV and KSHV miRNAs have been previously identified, the specific functions of these miRNAs during in vivo infection are largely unknown. Murine gammaherpesvirus 68 (MHV68) is a natural pathogen of rodents that is genetically related to both EBV and KSHV, and thus serves as an excellent model for the study of EBV and KSHV genetic elements such as miRNAs in the context of infection and disease. However, the specific targets of MHV68 miRNAs remain completely unknown. Using a technique known as qCLASH (quick crosslinking, ligation, and sequencing of hybrids), we have now identified thousands of Ago-associated, direct miRNA-mRNA interactions during lytic infection, latent infection and reactivation from latency. Validating this approach, detailed molecular analyses of specific interactions demonstrated repression of numerous host mRNA targets of MHV68 miRNAs, including Arid1a, Ctsl, Ifitm3 and Phc3. Notably, of the 1,505 MHV68 miRNA-host mRNA targets identified in B cells, 86% were shared with either EBV or KSHV, and 64% were shared among all three viruses, demonstrating significant conservation of gammaherpesvirus miRNA targeting. Pathway analysis of MHV68 miRNA targets further revealed enrichment of cellular pathways involved in protein synthesis and protein modification, including eIF2 Signaling, mTOR signaling and protein ubiquitination, pathways also enriched for targets of EBV and KSHV miRNAs. These findings provide substantial new information about specific targets of MHV68 miRNAs and shed important light on likely conserved functions of gammaherpesvirus miRNAs.

Indexed as

Protein Processing, Post-TranslationalAnimalsGammaherpesvirinaeGene Expression RegulationHerpesviridae InfectionsMiceMicroRNAsRNA, MessengerRNA, ViralTOR Serine-Threonine KinasesTranscription FactorsVirus ReplicationELF2 protein, humanMicroRNAsMTOR protein, humanRNA, MessengerRNA, ViralTOR Serine-Threonine KinasesTranscription Factors

Identifiers

PMID31393953
PMCPMC6687095
OpenAlexW2968769578

What OpenQuestion holds

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LicenceCC BY
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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.