The differential regulation of nitric oxide by Herpes simplex virus-1 and-2 in a corneal epithelial cell line

Herpes simplex keratitis is a significant cause of blindness worldwide. Nit ric oxide (NO) has been shown to play a role in non-specific defence mechan isms and cell signalling in bacterial and parasitic infections. We investig ated if Herpes simplex virus (HSV) isolated from keratitis could induce NO production. Human corneal epithelial cells were infected with high (multipl icity of infection; MOI 0.4) and low (MOI 0.04) HSV-1 and HSV-2 concentrati ons. Culture supernatants were collected at 1 h, 4 h, 8 h, 12 h and 24 h po st-challenge. Samples were prepared by removal of proteins by ultrafiltrati on. Production of NO was measured using nitrite and nitrate assays. Herpes simplex virus-1 downregulated the production of NO, while HSV-2 upregulated NO production. Downregulation of NO could be a survival strategy against t he cytotoxic action of NO, to eliminate infected cells. Upregulation of NO production may be associated with the presence of glycoproteins on the vira l coat, which have been shown to induce NO in other disease conditions. Fur ther studies are required to confirm the role of NO in viral keratitis.