CYTOKINE-MEDIATED SURVIVAL FROM LETHAL HERPES-SIMPLEX VIRUS-INFECTION- ROLE OF PROGRAMMED NEURONAL DEATH

The mechanisms responsible for cytokine-mediated antiviral effects are not fully understood. We approached this problem by studying the outc ome of intraocular herpes simplex (HSV) infection in transgenic mice t hat express interferon gamma in the photoreceptor cells of the retina. These transgenic mice showed selective survival from lethal HSV-2 inf ection manifested in both eyes, the optic nerve, and the brain. Althou gh transgenic mice developed greater inflammatory responses to the vir us in the eyes, inflammation and viral titers in their brains were equ ivalent to nontransgenic mice. However, survival of transgenic mice co rrelated with markedly lower numbers of central neurons undergoing apo ptosis. The protooncogene Bcl2 was found to be induced in the HSV-2-in fected brains of transgenic mice, allowing us to speculate on its role in fostering neuronal survival in this model. These observations impl y a complex interaction between cytokine, virus, and host cellular fac tors. Our results suggest a cytokine-regulated salvage pathway that al lows for survival of infected neurons.