MOLECULAR BIOLOGY OF VARICELLA-ZOSTER VIRUS INFECTIONS

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Primary infection with varicella-zoster virus (VZV) causes chickenpox, and reactivation of the virus from latency results in zoster. The goals of this project are to identify and determine the function of VZV genes that are expressed during active infection and during latency in the body. We are currently investigating the functions of VZV genes that regulate viral gene expression. Analysis of VZV gene products during acute infection indicate that at least five VZV genes, ORF4, ORF1O, ORF6l, ORF62, and ORF63, transactivate the expression of other VZV genes in vitro. Two of these genes (ORFlO, ORF62) activate transcription directly and their activation domains have been identified. Three of these vzv genes (ORF1O, ORF61, and ORF62) can complement the function of their herpes simplex virus homologs, while one of the genes (ORF4) cannot. Chimeric proteins, containing portions of VZV proteins and their HSV-1 homologs, have been constructed to compare functional domains of these proteins. Two VZV genes, ORF28 and ORF29, have bidirectional, overlapping promoters that regulate their expression. These control elements are activated by a viral protein (ORF62) and a cellular protein termed USF. While both of these genes are expressed in acute infection, one of the genes (ORF29) is expressed during dormant infection, while the other gene (ORF28) is not. Analysis of trigeminal ganglia from human cadavers without active evidence of VZV infection indicates that at least two VZV genes (ORF29 and ORF62) are expressed during viral latency, while other genes (ORF1O, ORF28, and ORF61) are not.