Although ocular infections with herpes simplex virus type 1 (HSV- 1) are a major cause of human corneal disease and blindness, as yet the mechanisms responsible for the pathological processes seen in association with HSV-1 induced ocular disease are not well- understood. An interesting pattern of bilateral ocular disease results when hsv-1 is inoculated into the anterior chamber of one eye of a BALB/c mouse. In the injected eye, there is an acute destructive inflammatory reaction in the anterior segment (cornea, anterior chamber) and anterior portion of the uveal tract (iris and ciliary body) which occurs within three days of virus inoculation. In spite of the massive anterior segment inflammation, severe inflammation, necrosis or choroidal infiltration occur rarely in the posterior segment of the injected eye. The uninoculated contralateral eye exhibits a delayed destructive reaction which is limited to the posterior segment of the injected eye. The uninoculated contralateral eye exhibits a delayed destructive reaction which is limited to the posteror segment (vitreous, retina, choroid). There is also a mild but non-progressive iridocytlitis in the uninjected eye. It is still unkown how much of the damage to the retina of the uninoculated eye is due to the direct cytopathic effects of the virus, how much is due to virus- specific host-mediated cytotoxicity towards virus-infected retinal cells and how much is due to non-specific damage to uninfected retinal cells by inflammation in the ocular compartment. Using the mouse model of herpes simplex virus retinitis, The aims of the research proposed herein are to: (1) use intertypic HSV-1/HSV-2 recombinant viruses to identify areas of the HSV-1 genome responsible for contralateral retinis; (2) defined the role of the HSV-1-injected eye in the pathogenesis of the retinitis in the uninoculated eye and the location of this virus in the uninoculated eye; and (4) determine the effect of specific and non-specific immune mediators and inflammatory processes on the progression of contralateral retinitis and subsequent necrosis. The goals of this project will be achieved by (1) molecular biological studies to analyze the genomes of HSV-1/HSV-2 recombinant viruses, (2) virological studies to locate (by in situ DNA:DNA hybridization and immunoperoxidase staining) and recover virus (by culture) from ocular and central nervous system structures, and (3) immunological studies to recover and characterize the cells that comprise the inflammatory infiltrate in the contralateral eye during the evolution of retinitis.
| Richter, Elizabeth R; Dias, James K; Gilbert 2nd, James E et al. (2009) Distribution of herpes simplex virus type 1 and varicella zoster virus in ganglia of the human head and neck. J Infect Dis 200:1901-6 |
| Cathcart, Heather M; Fields, Mark A; Zheng, Mei et al. (2009) Infiltrating cells and IFNgamma production in the injected eye after uniocular anterior chamber inoculation of HSV-1. Invest Ophthalmol Vis Sci 50:2269-75 |
