Our laboratory studies the mechanisms of herpes simplex virus productive infection of epithelial cells and latent infection of neuronal cells and the host immune response to HSV infection. Studies of productive infection involve the mechanisms of regulation of viral gene expression and intranuclear localization of viral regulatory and DNA replication proteins. Our work on latent infection has identified novel gene regulatory pathways in neurons that lead to nonpermissive infection. Our studies of the host immune responses to HSV have led to the development of genetically engineered replication-defective mutant HSV-2 strains as candidate vaccines for genital herpes and as vectors for AIDS vaccines. We are also using HSV vectors to express prostate cancer antigens as potential cancer vaccines, and we are participating in the study and design of HSV strains that specifically kill tumor cells.