MOLECULAR BIOLOGY OF VARICELLA-ZOSTER VIRUS INFECTIONS

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Varicella-zoster virus causes chickenpox on primary infection, and zoster during reactivation from viral latency. The goals of this project are to identify and determine the function of varicella-zoster virus (VZV) genes that are expressed during active infection and during latency in the body. RNA transcripts corresponding to immediate-early and early VZV genes have been detected in human trigeminal ganglia using in situ hybridization and Northern analysis. At present, we mapping transcripts from these VZV genes and assaying their ability to regulate expression of other VZV genes by transient expression assays in vitro. VZV genes that are expressed during active infection and regulate viral gene expression are being studied. The transcriptional activation or repression domains of two of these regulatory proteins are being mapped. Cell lines have been constructed that stably express several of these VZV proteins and we are analyzing the effect of these proteins during infection of the cells with wild-type VZV or herpes simplex virus mutants. In addition cell lines are being constructed that secrete VZV glycoproteins which will be useful for evaluating the immune response to VZV and may be useful for generating subunit vaccines. Finally, we are constructing VZV mutants which are deleted for several of these regulatory genes or for genes encoding viral glycoproteins. Analysis of these viral mutants in cell culture and in animal models should provide further information on the role of individual VZV genes in active infection and during latency.