Abstract
Abstract: :
PURPOSE: Sight threatening corneal opacification and neovascularization are manifestations of recurrent herpetic corneal disease in patients with latent ocular herpes simplex virus (HSV) infection. The corneal stromal inflammation that causes these lesions is known as herpetic stromal keratitis (HSK) and results from the interplay of cytokines produced by cells in the herpes infected, inflamed eye. In primary HSK, interferon–γ (IFN–γ) may help control viral replication and contribute to corneal pathology. Its role in recurrent HSK is unknown and is the focus of the present study. METHODS: Normal and IFN–γ gene knockout (IFN–γ KO) C57BL/6 mice were infected on the scarified cornea with 106 PFU HSV–1 McKrae strain and administered anti–HSV antiserum to limit ocular morbidity and death. Five weeks after primary infection, eyes of mice with latent ocular HSV infection were UV–B irradiated to stimulate viral recrudescence. Subsequently, eyes were monitored for viral shedding (reactivation) and pathology. Results: IFN–γ KO mice had a greater incidence and severity of opacity, neovascularization, and blepharitis following viral reactivation. The percentage of latently infected eyes that shed virus after UV–B exposure was greater (16/19–84%) in IFN–γ KO mice than in normal mice (11/19–58%), and shedding was prolonged in the IFN–γ KO groups. Additionally, tear film virus titers were higher in IFN–γ KO mice than in normal mice. Diminished delayed type hypersensitivity responses in KO mice confirmed their IFN–γ deficiency. CONCLUSIONS: Enhanced recurrent viral shedding and disease in IFN–γ KO mice may indicate a role for IFN–γ in viral clearance during primary infection –that leads to greater virus load in latency, and/or during recurrent infection –that directly exacerbates disease. While preliminary data shows that anti– IFN–γ antibody treatment of latently infected normal mice worsens post–reactivation corneal pathology, investigation into anti–viral and immunolopathologic properties of IFN–γ in recurrent HSK continues.
Keywords: cornea: basic science • herpes simplex virus • cytokines/chemokines