Investigations of neurobiological and virological functions important for the establishment of herpes simplex virus (HSV) latent infections of sensory ganglion neurons, and of functions important for the reactivation of such infections are proposed. Latent HSV infections are common in humans, and provide the substrate for recurrent oral and genital HSV infections. Latent HSV infections occur in neurons and it is likely that neuronal functions are of importance in the establishment of latency and in viral reactivation. We propose that appropriate neurological studies of sensory ganglion neurons will provide important insights into this pathological state.
Two specific aims will be addressed in this project in studies of: (1) parameters of the mouse model of HSV latency, and (2) neuronal control of HSV reactivation. In the first group of studies we will investigate viral factors, including amounts of HSV inoculated necessary for latency and for the detection of viral DNA and RNA in ganglia. These studies will provide important information and also will provide a basis of comparison for studies of HSV mutants performed by other investigators in this Program Project. In our second area of emphasis, we will investigate reactivation of latent HSV in vivo following neurobiological manipulation of latently infected neurons. In preliminary studies, evidence of HSV reactivation following nerve section has been noted. These studies will be continued; specifically, the block of virus reactivation by antivirals and examination of viral-specified RNAs and proteins that occur with reactivation. We also will determine whether HSV reactivation occurs after ganglion root sections and whether establishment of latent infections can be prevented by early nerve section. The effect of conditioning nerve section on latency and reactivation will also be investigated. It is expected that by this interdisciplinary virological and neurobiological approach, viral and neuronal factors important for HSV latency and reactivation will be determined.
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