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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Activation of Checkpoint Kinase 2 Is Critical for Herpes Simplex Virus Type 1 Replication in Corneal Epithelium
Ophthalmic research, v 53(2), pp 55-64
01 Jan 2015
PMCID: PMC4380435
PMID: 25531207
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background/Aims: Herpes simplex virus (HSV) type I keratitis remains a leading cause of corneal morbidity, despite the availability of effective antiviral drugs. Improved understanding of virus-host interactions at the level of the host DNA damage response (DDR), a known factor in the development of HSV-1 keratitis, may shed light on potential new therapeutic targets. This report examines the role of checkpoint kinase 2 (Chk2), a DDR mediator protein, in corneal epithelial HSV-1 infection. Methods: A small-molecule inhibitor of Chk2 (Chk2 inhibitor II) was applied to HSV-1-infected cultured human corneal epithelial cells (hTCEpi and HCE) as well as to explanted and organotypically cultured human and rabbit corneas. Infection levels were assessed by plaque assay and real-time PCR. RNAi-mediated depletion of Chk2 was performed to confirm the effect of the inhibitor. Results: Inhibition of the Chk2 kinase activity greatly suppresses the cytopathic effect, genome replication and infectious progeny production in vitro and ex vivo. Conclusion: This report demonstrates the critical role of Chk2 kinase in the establishment of HSV-1 corneal epithelial infection. These data contribute to our understanding of herpesvirus-host interactions and underscore the significance of DDR activation in HSV-1 keratitis. (C) 2014 S. Karger AG, Basel
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Details
- Title
- Activation of Checkpoint Kinase 2 Is Critical for Herpes Simplex Virus Type 1 Replication in Corneal Epithelium
- Creators
- Oleg Alekseev - Drexel UniversityVladimir Limonnik - Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USAKelly Donovan - Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USAJane Azizkhan-Clifford - Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA
- Publication Details
- Ophthalmic research, v 53(2), pp 55-64
- Publisher
- Karger
- Number of pages
- 10
- Grant note
- Drexel University College of Medicine F30DK094612 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) 1F30DK094612-O1A1 / NRSA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000350268300001
- Scopus ID
- 2-s2.0-84924265699
- Other Identifier
- 991019168232604721
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- Web of Science research areas
- Ophthalmology