Suppression of transcription factor early growth response 1 reduces herpes simplex virus 1-induced corneal disease in mice.
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.
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Hui-Wen
HW
Yao
Shih-Heng
SH
Chen
Ching
C
Li
Yuk-Ying
YY
Tung
Shun-Hua
SH
Chen
D000818:Animals; D003315:Cornea / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors*; D005260:Female; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D016849:Keratitis, Herpetic / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic; D014157:Transcription Factors; D014779:Virus Replication
D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D014157:Transcription Factors