The mechanisms of binding and entry of alphaherpesviruses are unclear. These early events in the herpesvirus life cycle are important to our understanding and our attempts to control herpesvirus diseases. We are investigating the binding of varicella-zoster virus (VZV) glycoproteins and glycoprotein B from herpes simplex virus type 2 (HSV-2) to cell membrane preparations from cultured cell lines, to isolated proteins, and to glycosaminoglycans. The genes for the major envelope glycoproteins of VZV have been cloned into high level expression vectors including the baculovirus expression system. Secreted soluble forms of the VZV gE and gI glycoproteins have been expressed in large amounts (milligram) to allow for biochemical, immunological, and functional studies of these proteins. The ability of these glycoproteins to inhibit VZV infections in vitro by binding to cell-surface receptors is being examined. Monoclonal antibodies to cell membrane proteins are being developed to identify specific cell surface membrane proteins that serve as receptors for VZV envelope glycoproteins. The immune response to these VZV glycoproteins is being investigated in a small animal model system. Soluble VZV glycoprotein B (VZV-gB) produced using the baculovirus expression system is being used to investigate the interaction of VZV-gB with heparin-like glycosaminoglycans. These interactions of VZV-gB are being compared with those of the HSV-2 homologous glycoprotein HSV-2-gB. These studies will lead to a detailed understanding of the affinity and specificity of the interactions of the VZV glycoproteins and of HSV-2-gB with their cell surface receptors that are important to disease processes of these herpesviruses.
