IMMUNITY TO HSV-1 INFECTION IN THE NERVOUS SYSTEM

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HSV-1 infections can produce recurrent viral lesions at the site of initial infection and has the ability to cause severe disease. Herpetic stromal keratitis (HSK) is one such disease caused by HSV-1 infection and is the leading cause of corneal blindness in humans within the United States. This disease is thought to be immune-mediated and several investigators have started to dissect the potential mechanisms involved. While many of these investigations have focused on immune mechanisms such as the presence or absence of cytokines on disease progression, very little has been done to determine the effects of these immune factors on viral gene regulation or replication within the sensory neuron which is known to harbor latent HSV-1. The mechanisms that control the latent state of HSV-1 remain elusive. The utilization of an in vitro neuronal model, developed in this laboratory, allows for the direct examination of the neuron and is useful for determining which immune factors contribute to the maintenance or reactivation of HSV-1 latently infected neurons. The effects of immune modulation and HSV-1 infection on the regulation of neuronal genes can also be examined using this system. The HSK mouse model will be used to stud) HSV-1 infection in vivo. Immune deficient mice will be used to determine if immune components, which are discovered in our studies to have an effect on maintenance or reactivation in the in vitro neuronal HSV-1 latency model are involved in the establishment, maintenance or reactivation of HSV- 1 infection in vivo. Understanding the events involved in the establishment of HSV latency and reactivation will conceivably lead to the development of immunotherapeutic techniques which may potentially ameliorate damaging immune responses or enhance the protective immune responses against infection with HSV-1.