Evidence map›Paper›PMID 29263259›Full record

ArticleJournal of virology2018

The ATM and Rad3-Related (ATR) Protein Kinase Pathway Is Activated by Herpes Simplex Virus 1 and Required for Efficient Viral Replication.

Terri G Edwards, David C Bloom, Chris Fisher

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

20 citing papers in PubMed, 30 citations in OpenAlex.

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  17. Article
  18. Early Nuclear Events after Herpesviral Infection.Journal of clinical medicine · 2019
    Review
  19. Coalescing replication compartments provide the opportunity for recombination between coinfecting herpesviruses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  20. Article
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

3 authors at 1 institution in 1 country.

Terri G EdwardsDepartment of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
David C BloomDepartment of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
Chris FisherDepartment of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA ctopherfis@ufl.edu.ORCID https://orcid.org/0000-0002-2461-1020
University of Florida · US

Funding

Pre-clinical Development of a Broad Spectrum Antiviral Compound to Treat Human PaR42AI068159 · NIAID · NANOVIR, LLC. · PI FISHER, CHRISTOPHER · 2010 to 2012
$3.0M
Pre-Clinical HPV16 Antiviral Compound DevelopmentR42AI062182 · NIAID · NANOVIR, LLC. · PI FISHER, CHRISTOPHER · 2008 to 2010
$2.9M
Regulation of lytic and latent infection by HSV-1 encoded miRNAsR01AI097376 · NIAID · UNIVERSITY OF FLORIDA · PI BLOOM, DAVID C. · 2012 to 2016
$1.9M
NIAID NIH HHS R01 AI097376NIAID NIH HHS R42 AI062182NIAID NIH HHS R42 AI068159
6 · The paper itself

Abstract

The ATM and Rad3-related (ATR) protein kinase and its downstream effector Chk1 are key sensors and organizers of the DNA damage response (DDR) to a variety of insults. Previous studies of herpes simplex virus 1 (HSV-1) showed no evidence for activation of the ATR pathway. Here we demonstrate that both Chk1 and ATR were phosphorylated by 3 h postinfection (h.p.i.). Activation of ATR and Chk1 was observed using 4 different HSV-1 strains in multiple cell types, while a specific ATR inhibitor blocked activation. Mechanistic studies point to early viral gene expression as a key trigger for ATR activation. Both pATR and pChk1 localized to the nucleus within viral replication centers, or associated with their periphery, by 3 h.p.i. Significant levels of pATR and pChk1 were also detected in the cytoplasm, where they colocalized with ICP4 and ICP0. Proximity ligation assays confirmed that pATR and pChk1 were closely and specifically associated with ICP4 and ICP0 in both the nucleus and cytoplasm by 3 h.p.i., but not with ICP8 or ICP27, presumably in a multiprotein complex. Chemically distinct ATR and Chk1 inhibitors blocked HSV-1 replication and infectious virion production, while inhibitors of ATM, Chk2, and DNA-dependent protein kinase (DNA-PK) did not. Together our data show that HSV-1 activates the ATR pathway at early stages of infection and that ATR and Chk1 kinase activities play important roles in HSV-1 replication fitness. These findings indicate that the ATR pathway may provide insight for therapeutic approaches.

Indexed as

Signal TransductionAtaxia Telangiectasia Mutated ProteinsCell LineCheckpoint Kinase 1DNA-Activated Protein KinaseDNA-Binding ProteinsHerpes SimplexHerpesvirus 1, HumanHumansImmediate-Early ProteinsNuclear ProteinsUbiquitin-Protein LigasesViral ProteinsVirus ReplicationAtaxia Telangiectasia Mutated ProteinsATM protein, humanATR protein, humanCheckpoint Kinase 1CHEK1 protein, humanDNA-Activated Protein KinaseDNA-Binding Proteinsherpes simplex virus, type 1 protein ICP4ICP27 protein, human herpesvirus 1ICP8 protein, SimplexvirusImmediate-Early ProteinsNuclear ProteinsPRKDC protein, humanUbiquitin-Protein LigasesViral ProteinsVmw110 protein, Human herpesvirus 1ATM and Rad3-related (ATR) kinaseATRChk1DNA damage responseherpes simplex virusviral replication

Identifiers

PMID29263259
PMCPMC5827400
OpenAlexW2778843889

What OpenQuestion 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 OpenQuestion graph.