The proposed research project focuses on the characterization of proteins involved in the Varicella zoster virus (VZV) DNA encapsidation process. Little work has been done on VZV assembly and in particular on the proteins involved in the cleavage and packaging of VZV DNA. The experiments proposed in the specific aims will (i) allow for the identification and characterization of the VZV encapsidation proteins and (ii) have the potential to better clarify our understanding of the protein-protein interactions involved in the process of DNA cleavage and packaging not only for VZV but for the Herpesviridae in general. Previous studies have shown that it is feasible to identify antiviral inhibitors that specifically target the encapsidation process of herpesviruses. Recently, a series of alpha-methylbenzyl thiourea compounds were described with specific anti-VZV activity. It appears that these compounds inhibit the VZV DNA encapsidation process and likely do so through an interaction with the VZV Open Reading Frame (ORF) 54 protein. Our laboratory has been fortunate to generate a background of information on the ORF54 gene/protein and begun to develop reagents to study the other encapsidation proteins. The studies proposed for this project will (i) characterize, for the first time, the proteins involved in DNA cleavage and packaging for VZV, (ii) further define the mechanism by which the alpha-methylbenzyl thiorurea inhibitors work and (iii) have the potential to define new antiviral drug targets within the DNA cleavage and packaging process. ? ?
