Evidence map›Paper›PMID 31789594›Full record

ArticleeLife2019

Herpesviral lytic gene functions render the viral genome susceptible to novel editing by CRISPR/Cas9.

Hyung Suk Oh, Werner M Neuhausser, Pierce Eggan, Magdalena Angelova, Rory Kirchner, Kevin C Eggan, David M Knipe

Abstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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, 1 synthesis or guideline pooled it.

  1. Pooled it
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  14. Therapeutic potentials of CRISPR-Cas genome editing technology in human viral infections.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022
    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

7 authors.

Hyung Suk Oh *Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, United States.ORCID 0000-0002-1739-0389
Werner M Neuhausser *Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States.ORCID 0000-0002-5092-2658
Pierce EgganDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States.
Magdalena AngelovaDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, United States.
Rory KirchnerDepartment of Biostatistics, Harvard TH Chan School of Public Health, Boston, United States.
Kevin C EgganDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States.
David M KnipeDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, United States.ORCID 0000-0003-1554-6236

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
CRISPR/Cas9 based antivirals for treatment of latent and lytic Herpesvirus-1 and -2 infection in vivoR21AI135423 · NIAID · HARVARD UNIVERSITY · PI EGGAN, KEVIN C · 2018 to 2019
$465k
Harvard Medical School Q-FASTR AwardNIAID NIH HHS P01 AI098681NIAID NIH HHS R21 AI135423NIH HHS P01 AI098681NIH HHS R21 AI135423
6 · The paper itself

Abstract

Herpes simplex virus (HSV) establishes lifelong latent infection and can cause serious human disease, but current antiviral therapies target lytic but not latent infection. We screened for sgRNAs that cleave HSV-1 DNA sequences efficiently in vitro and used these sgRNAs to observe the first editing of quiescent HSV-1 DNA. The sgRNAs targeted lytic replicating viral DNA genomes more efficiently than quiescent genomes, consistent with the open structure of lytic chromatin. Editing of latent genomes caused short indels while editing of replicating genomes produced indels, linear molecules, and large genomic sequence loss around the gRNA target site. The HSV ICP0 protein and viral DNA replication increased the loss of DNA sequences around the gRNA target site. We conclude that HSV, by promoting open chromatin needed for viral gene expression and by inhibiting the DNA damage response, makes the genome vulnerable to a novel form of editing by CRISPR-Cas9 during lytic replication.

Indexed as

Gene EditingGenes, ViralAnimalsBase SequenceCell LineCRISPR-Associated Protein 9CRISPR-Cas SystemsDNA RepairDNA, ViralGene Expression Regulation, ViralHerpesviridaeHerpesvirus 1, HumanHumansModels, GeneticMutagenesisRNA, Guide, CRISPR-Cas SystemsCRISPR-Associated Protein 9DNA, ViralRNA, Guide, CRISPR-Cas SystemsCRISPRgeneticsGenome editinggenomicsherpes simplex virusinfectious diseaselatent infectionlytic replicationmicrobiologyreactivationvirus

Identifiers

PMID31789594
PMCPMC6917492

What OpenQuestion holds

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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.