We study the molecular genetics, pathogenesis, and clinical aspects of human herpesviruses, including Epstein-Barr virus (EBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV). The laboratory focuses on vaccine development, genes important for virus entry and replication, and identification of cellular mutations in patients with severe herpesvirus infections. Recent findings include development of candidate vaccines for HSV and rhesus EBV; identification of cellular genes that predispose to severe EBV infections; discovery of cells in the blood, other than B cells, that are infected by EBV; and a novel entry molecule for VZV into cells. Clinical projects complement the laboratory studies. These include a Phase I study of a replication defective herpes simplex virus vaccine, studies of patients with severe virus infections to define genetic mutations or polymorphisms associated with the disease, studies of patients with EBV diseases, studies of immune responses in persons after vaccination with the smallpox or varicella vaccines, and attempts to identify novel viruses in patients with unexplained syndromes.