Primary infection with varicella-zoster virus (VZV) causes chickenpox, and reactivation of the virus from latency results in zoster. The purpose of this project is to study the molecular basis for the pathogenesis and latency of VZV. We have developed a rodent model to study VZV latency. Inoculation of rodents with VZV by the intramuscular route results in a latent infection in the central nervous system of most of the animals. Viral DNA and RNA can be detected in ganglia from the animals at least one month after inoculation. The pattern of latent infection in the animals resembles that seen in humans naturally infected with the virus. We have found that both wild-type and vaccine strains of VZV become latent in the nervous system of these animals. We have developed a series of VZV mutants, which lack individual VZV genes, and we are testing which genes are required for latent infection. We have determined that several genes can be deleted from VZV and that the """"""""knock-out"""""""" viruses are still able to establish a latent infection in the nervous system with expression of viral RNA. We have identified the product of a new VZV gene (ORF65) and have shown that it encodes a protein that localizes to the Golgi apparatus of infected cells. The VZV protein is phosphorylated by a cellular protein kinase, termed casein kinase II. The protein forms part of the structure of the virion. Deletion of this gene from the virus does not impair the growth of the virus in cell culture.
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