HSV-1 continues to be a threat of morbidity and mortality worldwide. Because the virus can maintain a reservoir in the human host through latency or dormancy, the virus is capable of reactivating causing both relatively benign effects, such as skin lesions, to severe corneal lesions leading to blindness and encephalitis, which can be fatal. HSV-1 can also cause severe effects in the immunocompromised individuals, such as AIDS patients. Although treatment with acyclovir can attenuate the productive infection, there is no known treatment for latently infected neurons. The latent infection maintains the viral reservoir that, with reactivation can spread the virus. Reactivation occurs most frequently following a stress stimulus, which include damage to the skin and fever. Hence, understanding the mechanisms controlling HSV-1 reactivation and latency is essential to potentially reduce reactivation and eradicate this virus from latently infected individuals.
The aim of this project is to determine the mechanism of reactivation during neuronal stress stimuli including nerve growth factor deprivation and heat shock. Preliminary results indicated that pro-apoptotic proteolytic enzyme, caspase-3 activation accelerates HSV-1 reactivation, indicating that apoptotic signaling is involved in viral reactivation. The project is designed to elucidate the signal transduction mechanism controlling reactivation induced by stress stimulus in neurons; this includes both neuronal and apoptosis specific signaling pathways.
