ArticleInvestigative ophthalmology & visual science2014
Inhibition of ataxia telangiectasia mutated (ATM) kinase suppresses herpes simplex virus type 1 (HSV-1) keratitis.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- The Host Cell Factor Phosphatase-2A Subunit PR130 Restricts Replication of Herpes Simplex Virus Type-1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DNA-PK and ATM drive phosphorylation signatures that antagonistically regulate cytokine responses to herpesvirus infection or DNA damage.Cell systems · 2024Article
- Cell Intrinsic Determinants of Alpha Herpesvirus Latency and Pathogenesis in the Nervous System.Viruses · 2023Review
- Nuclear antiviral innate responses at the intersection of DNA sensing and DNA repair.Trends in microbiology · 2022Review
- Transcriptomic analysis revealed increased expression of genes involved in keratinization in the tears of COVID-19 patients.Scientific reports · 2021Article
- Blocking HSV-1 glycoprotein K binding to signal peptide peptidase reduces virus infectivity in vitro and in vivo.PLoS pathogens · 2021Article
- Inflammasome, the Constitutive Heterochromatin Machinery, and Replication of an Oncogenic Herpesvirus.Viruses · 2021Review
- Herpes Simplex Virus 1 Manipulates Host Cell Antiviral and Proviral DNA Damage Responses.mBio · 2021Article
- Targeting Host Cellular Factors as a Strategy of Therapeutic Intervention for Herpesvirus Infections.Frontiers in cellular and infection microbiology · 2021Review
- Monocaprin eye drop formulation to combat antibiotic resistant gonococcal blindness.Scientific reports · 2020Article
- HSV-1 Hijacks the Host DNA Damage Response in Corneal Epithelial Cells through ICP4-Mediated Activation of ATM.Investigative ophthalmology & visual science · 2020Article
- Combination Therapy with Reovirus and ATM Inhibitor Enhances Cell Death and Virus Replication in Canine Melanoma.Molecular therapy oncolytics · 2019Article
- ATM and ATR Expression Potentiates HBV Replication and Contributes to Reactivation of HBV Infection upon DNA Damage.Viruses · 2019Article
- Article
- H2AX phosphorylation and DNA damage kinase activity are dispensable for herpes simplex virus replication.Virology journal · 2016Article
- Establishment of a novel therapeutic vector targeting the trigeminal ganglion in rats.Drug design, development and therapy · 2016Article
- Pattern recognition receptors in microbial keratitis.Eye (London, England) · 2015Review
- HSV-I and the cellular DNA damage response.Future virology · 2015Article
- Activation of checkpoint kinase 2 is critical for herpes simplex virus type 1 replication in corneal epithelium.Ophthalmic research · 2015Article
- O-GlcNAc modification of transcription factor Sp1 mediates hyperglycemia-induced VEGF-A upregulation in retinal cells.Investigative ophthalmology & visual science · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeHerpes keratitis (HK) remains the leading cause of cornea-derived blindness in the developed world, despite the availability of effective antiviral drugs. Treatment toxicity and the emergence of drug resistance highlight the need for additional therapeutic approaches. This study examined ataxia telangiectasia mutated (ATM), an apical kinase in the host DNA damage response, as a potential new target for the treatment of HK.
methodsSmall molecule inhibitor of ATM (KU-55933) was used to treat herpes simplex virus type 1 (HSV-1) infection in three experimental models: (1) in vitro--cultured human corneal epithelial cells, hTCEpi, (2) ex vivo--organotypically explanted human and rabbit corneas, and (3) in vivo--corneal infection in young C57BL/6J mice. Infection productivity was assayed by plaque assay, real-time PCR, Western blot, and disease scoring.
resultsRobust ATM activation was detected in HSV-1-infected human corneal epithelial cells. Inhibition of ATM greatly suppressed viral replication in cultured cells and in explanted human and rabbit corneas, and reduced the severity of stromal keratitis in mice. The antiviral effect of KU-55933 in combination with acyclovir was additive, and KU-55933 suppressed replication of a drug-resistant HSV-1 strain. KU-55933 caused minimal toxicity, as monitored by clonogenic survival assay and fluorescein staining.
conclusionsThis study identifies ATM as a potential target for the treatment of HK. ATM inhibition by KU-55933 reduces epithelial infection and stromal disease severity without producing appreciable toxicity. These findings warrant further investigations into the DNA damage response as an area for therapeutic intervention in herpetic ocular diseases.
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