EGFP-Tagged VZV for the Study of Neuronal Infection

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DESCRIPTION (provided by applicant): Varicella-zoster virus (VZV) is a member of the herpesvirus family. Infection with VZV causes chickenpox, which typically resolves on its own. Following primary infection, VZV establishes lifelong latency in neurons within the dorsal root ganglia of the host. Later in life, VZV can reactivate from latency and re-infect the skin to cause shingles. After resolution of the acute symptoms, a substantial proportion of shingles patients develop long-lasting, severe pain at the site of the rash referred to postherpetic neuralgia (PHN). PHN is highly resistant to medical therapy making it a particularly debilitating illness that can persist for years. Shingles, PHN and other diseases resulting from VZV reactivation are common and cause substantial morbidity. Valuable insights into herpesvirus infection of neurons have been provided by studies of HSV-1 and PRV. However, the unique clinical syndromes caused by VZV reactivation as well as its distinctive growth properties in cultured cells emphasize the need for direct studies of this pathogen in neuronal tissue. To date no studies have been reported addressing the molecular biology of VZV assembly and egress in nerve cells. The goal of the proposed experiments is to facilitate such studies by generating fluorescent tagged VZV recombinant viruses and assessing their ability to infect and express the fluorescent proteins in cultured neurons. Successful completion of these studies will result in reagents and the development of techniques that will open new avenues of research into the molecular biology of VZV pathogenesis.