Evidence map›Paper›PMID 23536669›Full record

ArticleJournal of virology2013

Mutational inactivation of herpes simplex virus 1 microRNAs identifies viral mRNA targets and reveals phenotypic effects in culture.

Omar Flores, Sanae Nakayama, Adam W Whisnant, Hassan Javanbakht, Bryan R Cullen, David C Bloom

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
6.6field-weighted citation impact, top 2% 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

65 citing papers in PubMed, 106 citations in OpenAlex.

  1. Article
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  13. Review
  14. Herpesviral Latency-Common Themes.Pathogens (Basel, Switzerland) · 2020
    Review
  15. Article
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  17. Article
  18. Article
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  20. Article

5 more citing papers are in PubMed but not listed here.

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 5 institutions in 1 country.

Omar FloresDepartment of Molecular Genetics and Microbiology and Center for Virology, Duke University Medical Center, Durham, North Carolina, USA.
Sanae Nakayama
Adam W Whisnant
Hassan Javanbakht
Bryan R Cullen
David C Bloom
University of Florida · USDuke Medical Center · USDuke University · USDuke University Hospital · USLa Roche College · US

Funding

Viral Oncology Training GrantT32CA009111 · NCI · DUKE UNIVERSITY · PI LUFTIG, MICAH A. · 1985 to 2023
$8.9M
Regulation of lytic and latent infection by HSV-1 encoded miRNAsR01AI097376 · NIAID · UNIVERSITY OF FLORIDA · PI BLOOM, DAVID C. · 2012 to 2016
$1.9M
NCI NIH HHS T32 CA009111NIAID NIH HHS R01 AI097376NIAID NIH HHS R01-AI097376
6 · The paper itself

Abstract

Herpes simplex virus 1 (HSV-1), a ubiquitous human pathogen, expresses several viral microRNAs (miRNAs). These, along with the latency-associated transcript, represent the only viral RNAs detectable in latently infected neuronal cells. Here, for the first time, we analyze which HSV-1 miRNAs are loaded into the RNA-induced silencing complex (RISC), the key effector of miRNA function. Only 9 of the 17 reported HSV-1 miRNAs, i.e., miR-H1 to miR-H8 plus miR-H11, were found to actually load into the RISC. Surprisingly, this analysis also revealed that HSV-1 miRNAs loaded into the RISC with efficiencies that differed widely; <1% of the miR-H1-3p miRNA detectable in HSV-1-infected cells was loaded into the RISC. Analysis of HSV-1 mutants individually lacking the viral miR-H2, miR-H3, or miR-H4 miRNA revealed that loss of these miRNAs affected the rate of replication of HSV-1 in neuronal cells but not in fibroblasts. Analysis of mRNA and protein expression, as well as assays mapping viral miRNA binding sites in infected cells, showed that endogenous HSV-1 miR-H2 binds to viral ICP0 mRNA and inhibits its expression, while endogenous miR-H4 inhibits the expression of the viral ICP34.5 gene. In contrast, no viral mRNA target for miR-H3 could be detected, even though miR-H3, like miR-H4, is perfectly complementary to ICP34.5 mRNA. Together, these data demonstrate that endogenous HSV-1 miRNA expression can significantly alter viral replication in culture, and they also identify two viral mRNA targets for miR-H2 and miR-H4 that can partially explain this phenotype.

Indexed as

MutationAnimalsBinding SitesCell LineFibroblastsGene Expression Regulation, ViralHEK293 CellsHerpesvirus 1, HumanHumansImmediate-Early ProteinsMiceMicroRNAsNeuronsNIH 3T3 CellsPhenotypeRabbitsgamma 34.5 protein, Human herpesvirus 1Immediate-Early ProteinsMicroRNAsRNA-Induced Silencing ComplexRNA, MessengerRNA, ViralUbiquitin-Protein LigasesViral ProteinsVmw110 protein, Human herpesvirus 1

Identifiers

PMID23536669
PMCPMC3676078
OpenAlexW2147495957

What Socratic 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 Socratic graph.