Rotaviruses are the major known etiologic agents of severe diarrhea in infants young children worldwide, and the need for the development of vaccines against rotavirus diseases has been widely acknowledged. The complete rotavirus particle contains three major structural components, enclosing the viral genome of eleven segments of double-stranded RNA. The goals of this project are two-fold: (i) to identify the viral genes that play a major role in virulence of rotaviruses by using a semi-homologous system of colostrum-deprived gnotobiotic newborn pigs and various reassortants of porcine rotavirus SB-1A strain (which causes diarrhea in gnotobiotic piglets) and human rotavirus DS-1 strain (which does not induce productive infection or diarrhea in gnotobiotic piglets), and (ii) to apply such information to the formulation of a strategy for the development of safe and effective rotavirus vaccines that are of optimal efficacy. In addition, this approach may expand our understanding of the mechanisms controlling rotavirus tissue tropism and replication in the gastrointestinal tract.