A major research obstacle in the study of the Norwalk-like human caliciviruses has been our inability to grow them in cell culture. The growth of Norwalk virus (NV) in cell culture would be a major advance in studies that address: (1) antigenic relationships among human caliciviruses; (2) identification of immune correlates of resistance to illness; (3) viral replication strategies of the Caliciviridae, unique single-stranded RNA viruses that have not been well characterized; (4) control of epidemic gastroenteritis by treatment or immunization; and (5) the epidemiology of human caliciviruses and the extent of their role in human diarrheal disease. Thus, a major goal of this project is to develop systems for study of the basic molecular biology and replication of these fastidious human pathogens.