Although HSV is a human pathogen mice can be infected with HSV, providing a reasonably good animal model for the study of HSV pathogenesis. The major goal of this proposal is to identify and characterize the cellular component that mediate infectious entry of HSV in mouse. The proposal outlines three basic aims. Firstly, HSV-1 entry mediator cDNAs will be identified and cloned either by a functional screening of mouse cDNA libraries or by homology search by PCR. For the latter approach primers designed against known human mediators will be used to screen mouse cDNA libraries. Secondly, a comparative study of mouse and human mediators will be made to define functional sites, domains, and specificity for different HSV strains. Finally, expression levels of mouse mediators will be determined for several mouse cell types and mediators used for HSV-1 entry identified. The results obtained from these experiments will contribute to the understanding of the herpesvirus infection and spread. A thorough understanding of herpesvirus infection should facilitate the development of treatment to prevent or eliminate herpesvirus infection.