Simian varicella virus (SVV) infection of primates and varicella-zoster virus (VZV) infection of humans share clinical, pathological, immunological and virological features. Both viruses become latent in ganglia at all levels of the neuraxis. Unlike any animal model of varicella latency, both VZV and SVV reactivate from latently infected ganglia of their natural host. Furthermore, human ganglia cannot be removed during life, while monkey ganglia containing latently infected or reactivated SVV can be analyzed before death in anaesthetized monkeys. These features provide a rationale for our hypothesis that the physical state of latent SVV in ganglia of monkeys naturally infected with SVV parallels VZV latency in humans, and that this model can be used to test immunosuppression as an effector ofvaricella reactivation. To test our hypothesis, we will identify all SVV genes that are transcribed and translated in intently infected monkey ganglia as wall as identify the calls within Intently infected monkey ganglia that harbor SVV. Also, based on clinical protocols currently being used that result in VZV reactivation in humans, we will analyze reactivation of latent SVV induced by x-irradiation, immunosuppressive drugs, and anti-inflammatory drug therapy, separately and in combinations. A more comprehensive knowledge of the physical state of latent and reactivated simian varicella virus, gained by testing our hypothesis, will lead to experiments designed to understand and prevent the cascade of events leading to human varicella reactivation, a cause of serious neurologic disease, particularly in the rapidly increasing elderly and immunocompromised populations.
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