Document Detail

The induction and suppression of the apoptotic response of HSV-1 in human corneal epithelial cells.
MedLine Citation:
PMID:  17251479     Owner:  NLM     Status:  MEDLINE    
PURPOSE: HSV-1 has been shown to block apoptosis in some cell lines when the cells are exposed to exogenous agents (e.g., sorbitol). The purpose of this study was to determine whether HSV-1 infection of human corneal epithelial (HCE) cells alone induces an early proapoptotic response and whether this response is subsequently downregulated during the infection. METHODS: HCE cells were infected with HSV-1 or subjected to osmotic shock (sorbitol). Fluorescent staining for annexin V binding, mitochondrial membrane potential, and DNA condensation and assays for caspase 8, 9, and 3 activity and cytokeratin 18 cleavage were performed, to assess the apoptotic pathway. RESULTS: HSV-1 infection of HCE cells induced a rapid proapoptotic response, characterized by translocation of phosphatidylserine to the external membrane, activation of caspases 8 and 3 within 2 hours, and cleavage of cytokeratin 18. However, the induced response was downregulated during the infection, and later stages of the apoptotic responses (e.g., DNA condensation) were not produced. Sorbitol treatment led to terminal apoptosis by 12 hours, as indicated by DNA condensation of treated cells and reduction in the number of viable cells. CONCLUSIONS: HSV-1 can induce and subsequently suppress the apoptotic pathway in HCE. Suppression of apoptosis occurred only during HSV-1 infection and not after treatment with sorbitol, suggesting that the suppression of apoptosis may be a mechanism of viral survival.
David H Miles; Archana Thakur; Nerida Cole; Mark D P Willcox
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  48     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-25     Completed Date:  2007-03-01     Revised Date:  2007-03-22    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  789-96     Citation Subset:  IM    
Vision Cooperative Research Centre, Sydney, Australia.
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MeSH Terms
Annexin A5 / metabolism
Caspase 3 / metabolism
Caspase 8 / metabolism
Cell Line
DNA / metabolism
Enzyme Inhibitors / pharmacology
Epithelium, Corneal / drug effects,  metabolism,  pathology,  virology*
Herpesvirus 1, Human / physiology*
Keratin-18 / metabolism
Membrane Potential, Mitochondrial
Microscopy, Fluorescence
Osmotic Pressure
Phosphatidylserines / metabolism
Protein Transport
Sorbitol / pharmacology
Reg. No./Substance:
0/Annexin A5; 0/Enzyme Inhibitors; 0/Keratin-18; 0/Phosphatidylserines; 50-70-4/Sorbitol; 9007-49-2/DNA; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8
Erratum In:
Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1000

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