Virus Name | Human herpesvirus 1 |
Virus Short Name | HSV1 |
Order | Herpesvirales |
Virus Family | Herpesviridae |
Virus Subfamily | Alphaherpesvirinae |
Genus | Simplexvirus |
Species | Herpes simplex virus 1 |
Host | Human, mammals |
Cell Tropism | Primary site of infection: epithelial mucosal cells , latency: remains latent in sensory neurons (ganglions) |
Associated Disease | Skin vesicles or mucosal ulcers, rarely encephalitis and meningitis |
Mode of Transmission | Contact, saliva |
VIPR DB link | http://www.viprbrc.org/brc/vipr_allSpecies_search.do?method=SubmitForm&decorator=herpes |
ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/91/herpesviridae |
Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Herpesviridae |
Paper Title | Activation of Checkpoint Kinase 2 Is Critical for Herpes Simplex Virus Type 1 Replication in Corneal Epithelium |
Author's Name | Oleg Alekseev, Vladimir Limonnik, Kelly Donovan, and Jane Azizkhan-Clifford |
Journal Name | Ophthalmic Research |
Pubmed ID | 25531207 |
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. |
Used Model | Human corneal epithelial cell |
DOI | 10.1159/000366228 |