Evidence map›Paper›PMID 25473037›Full record

ArticleScience translational medicine2014

Inhibition of LSD1 reduces herpesvirus infection, shedding, and recurrence by promoting epigenetic suppression of viral genomes.

James M Hill, Debra C Quenelle, Rhonda D Cardin, Jodi L Vogel, Christian Clement, Fernando J Bravo, Timothy P Foster, Marta Bosch-Marce, Priya Raja, Jennifer S Lee and 4 more

Abstract read
In one paragraph

Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
7.1field-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

69 citing papers in PubMed, 86 citations in OpenAlex.

  1. Article
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  4. Article
  5. Review
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  8. Article
  9. Article
  10. Article
  11. Strategies that regulate LSD1 for novel therapeutics.Acta pharmaceutica Sinica. B · 2024
    Review
  12. Article
  13. Discovery of Pyrrolo[2,3-ACS medicinal chemistry letters · 2023
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Histone modifiers at the crossroads of oncolytic and oncogenic viruses.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  20. Article

9 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

14 authors at 3 institutions in 1 country.

James M HillDepartment of Ophthalmology and Department of Microbiology, Immunology, and Parasitology, LSU Eye Center, Louisiana State University Health Science Center School of Medicine, New Orleans, LA 70112, USA.
Debra C QuenelleDepartment of Pediatric Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Rhonda D CardinDivision of Infectious Diseases, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
Jodi L VogelNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Christian ClementDepartment of Ophthalmology and Department of Microbiology, Immunology, and Parasitology, LSU Eye Center, Louisiana State University Health Science Center School of Medicine, New Orleans, LA 70112, USA.
Fernando J BravoDivision of Infectious Diseases, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
Timothy P FosterDepartment of Ophthalmology and Department of Microbiology, Immunology, and Parasitology, LSU Eye Center, Louisiana State University Health Science Center School of Medicine, New Orleans, LA 70112, USA.
Marta Bosch-MarceCenter for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20852, USA.
Priya RajaDepartment of Microbiology and Immunology, Harvard Medical School, Boston, MA 02115, USA.
Jennifer S LeeDepartment of Microbiology and Immunology, Harvard Medical School, Boston, MA 02115, USA. Harvard Program in Virology, Harvard Medical School, Boston, MA 02115, USA.
David I BernsteinDivision of Infectious Diseases, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
Philip R KrauseCenter for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20852, USA.
David M KnipeDepartment of Microbiology and Immunology, Harvard Medical School, Boston, MA 02115, USA. Harvard Program in Virology, Harvard Medical School, Boston, MA 02115, USA.
Thomas M KristieNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. tkristie@niaid.nih.gov.
Harvard University · USCenter for Biologics Evaluation and Research · USNational Institute of Allergy and Infectious Diseases · US

Funding

VIral and host mechanisms that tilt the HSV lytic/latent balanceP01AI098681 · NIAID · HARVARD MEDICAL SCHOOL · PI PESOLA, JEAN M · 2013 to 2023
$19.2M
Transcriptional control of herpes simplex virus lytic infection and latency-reactivation cyclesZIAAI000712 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI KRISTIE, THOMAS M · 2009 to 2025
$13.0M
HCF-1, A Mammalian Factor Controlling HSV Gene ExpressionZIAAI000711 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI KRISTIE, THOMAS M · 2009 to 2017
$5.4M
OCULAR HSV: LATENCY, REACTIVATION, &RECURRENCER01EY006311 · NEI · LSU HEALTH SCIENCES CENTER · PI LUKIW, WALTER J · 1985 to 2012
$5.3M
NOVEL MAMMALIAN TRANSCRIPTION FACTOR INVOLVED IN HSV GENE EXPRESSIONZ01AI000711 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI KRISTIE, THOMAS M · 1994 to 2008
$1.3M
Regulation Of Transcription Of Herpes Simplex VirusZ01AI000712 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI KRISTIE, THOMAS M · 1994 to 2008
$847k
Intramural NIH HHS Z01 AI000711Intramural NIH HHS Z01 AI000712NEI NIH HHS R01 EY006311NEI NIH HHS R01-EY006311NIAID NIH HHS HHSN272201000027CNIAID NIH HHS P01 AI098681NIAID NIH HHS P01-AI098681
6 · The paper itself

Abstract

Herpesviruses are highly prevalent and maintain lifelong latent reservoirs, thus posing challenges to the control of herpetic disease despite the availability of antiviral pharmaceuticals that target viral DNA replication. The initiation of herpes simplex virus infection and reactivation from latency is dependent on a transcriptional coactivator complex that contains two required histone demethylases, LSD1 (lysine-specific demethylase 1) and a member of the JMJD2 family (Jumonji C domain-containing protein 2). Inhibition of either of these enzymes results in heterochromatic suppression of the viral genome and blocks infection and reactivation in vitro. We demonstrate that viral infection can be epigenetically suppressed in three animal models of herpes simplex virus infection and disease. Treating animals with the monoamine oxidase inhibitor tranylcypromine to inhibit LSD1 suppressed viral lytic infection, subclinical shedding, and reactivation from latency in vivo. This phenotypic suppression was correlated with enhanced epigenetic suppression of the viral genome and suggests that, even during latency, the chromatin state of the virus is dynamic. Therefore, epi-pharmaceuticals may represent a promising approach to treat herpetic diseases.

Indexed as

Epigenesis, GeneticAnimalsDisease Models, AnimalFemaleGenome, ViralGuinea PigsHerpesviridae InfectionsHistone DemethylasesMiceMice, Inbred BALB CMonoamine Oxidase InhibitorsOxidoreductases, N-DemethylatingPhenotypeProtein Structure, TertiaryRabbitsRecurrenceHistone DemethylasesKDM1a protein, mouseMonoamine Oxidase InhibitorsOxidoreductases, N-DemethylatingTranylcypromine

Identifiers

PMID25473037
PMCPMC4416407
OpenAlexW2110020189

What OpenQuestion holds

Textmetadata
LicenceTDM
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.