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. Nitric oxide (NO) has been shown to play a role in non-specific defence mechanisms and cell signalling in bacterial and parasitic infections. We investigated if Herpes simplex virus (HSV) isolated from keratitis could induce NO production. Human corneal epithelial cells were infected with high (multiplicity of infection; MOI 0.4) and low (MOI 0.04) HSV-1 and HSV-2 concentrations. Culture supernatants were collected at 1 h, 4 h, 8 h, 12 h and 24 h post-challenge. Samples were prepared by removal of proteins by ultrafiltration. 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 the cytotoxic action of NO, to eliminate infected cells. Upregulation of NO production may be associated with the presence of glycoproteins on the viral coat, which have been shown to induce NO in other disease conditions. Further studies are required to confirm the role of NO in viral keratitis.