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Publication : Suppression of transcription factor early growth response 1 reduces herpes simplex virus 1-induced corneal disease in mice.

First Author  Yao HW Year  2012
Journal  J Virol Volume  86
Issue  16 Pages  8559-67
PubMed ID  22647700 Mgi Jnum  J:186165
Mgi Id  MGI:5431148 Doi  10.1128/JVI.00505-12
Citation  Yao HW, et al. (2012) Suppression of transcription factor early growth response 1 reduces herpes simplex virus 1-induced corneal disease in mice. J Virol 86(16):8559-67
abstractText  Herpes simplex virus 1 replication initiates angiogenesis and inflammation in the cornea. This can result in herpetic stromal keratitis (HSK), which is a leading cause of infection-induced corneal blindness. Host cellular factors mediate the progression of HSK, but little is known about these cellular factors and their mechanisms of action. We show here that the expression of the cellular transcription factor early growth response 1 (Egr-1) in HSV-1-infected mouse corneas was enhanced. Enhanced Egr-1 expression aggravated HSK by increasing viral replication and subsequent neovascularization with high levels of potent angiogenic factors, fibroblast growth factor 2, and vascular endothelial growth factor. Furthermore, Egr-1 deficiency due to a targeted disruption of the gene or knockdown of Egr-1 expression topically using a DNA-based enzyme significantly reduced HSK by decreasing both viral replication and the angiogenic response. The present study provides the first evidence that endogenous Egr-1 aggravates HSK and that blocking Egr-1 reduces corneal damage.
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