Abstract
Herpes simplex virus type 1 (HSV-1) causes a latent infection in sensory ganglia neurons in humans and in the mouse model. The ability of the virus to latently infect neurons and reactivate is central to the ability of HSV-1 to remain in the human population and spread to new hosts. It is possible that neuronal transcriptional proteins control latency and reactivation by modulating activation of the HSV-1 immediate-early (IE) gene ICP0. We have previously shown that factors in trigeminal ganglia neurons can differentially activate the IE ICP0 promoter and the IE ICP4 promoter in developing trigeminal ganglia neurons of transgenic mice. Ultraviolet (UV) irradiation and hyperthermic stress have been shown to result in HSV-1 reactivation from sensory neurons in the mouse model. Reporter transgenic mice were exposed to UV irradiation or hyperthermia to test whether stimuli that are known to reactivate HSV-1 could activate viral IE promoters in the absence of viral proteins. Measurement of g -galactosidase activity in trigeminal ganglia from these transgenic mice indicated that the ICP0 promoter activity was significantly increased by both UV irradiation and hyperthermia. The IE genes ICP4 and ICP27 and the late gene gC reporter transgenes failed to be activated in parallel experiments. These results suggest that the ICP0 promoter is a target for activation by host transcription factors in sensory neurons that have undergone damage. It further suggests the possibility that activation of ICP0 gene expression by neuronal transcription factors may be important in reactivation of HSV-1 in neurons.