The Role of Humoral Immunity in The Resolution of Rotavirus Infection in Mice

264 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1987.The immune response to rotaviruses has been studied extensively in several animal species. However, the importance of a humoral immune response in the resolution of active rotavirus infection has not been investigated directly. Most animals became resistant to rotavirus-induced diarrhea after a certain age. The study of host factors, such as the intestinal antibody response, involved in the resolution of virus infection in the neonate may shed light on the mechanisms of age-dependent resistance to disease. The mouse offers a unique opportunity to study the role of virus-specific intestinal antibodies in resolution because most, if not all, antibodies in the neonatal intestine during the course of infection are passively acquired in milk via suckling.In two sequential studies, murine rotavirus infection in neonatal Balb/c mice was characterized chronologically by: (1) signs of diarrhea, (2) virus antigen excretion in feces, (3) histologic lesions in the intestine, and (4) rotavirus antigen expression in the intestinal epithelium. Antirotavirus antibodies titers were measured in the sera, stomach milk curds, and intestinal contents of the infected neonates and in the sera of their dams. The first study showed that virus-specific antibodies were present in milk and intestinal contents after 4 days postinfection (pi), while diarrhea and histologic lesions resolved at 8 days pi and rotavirus antigen was cleared from the intestinal epithelium and feces at 8 to 10 days pi. In the second study, the course of rotavirus infection in neonatal mice allowed to acquire antirotavirus antibodies in milk was compared to the course of infection in mice denied milk antibodies, so that the importance of passively acquired, lactogenic humoral immunity in resolution could be assessed. There was no difference in times of resolution of infection and disease between mice which received milk antibodies and mice which did not. Therefore, rotavirus-specific intestinal antibodies were not important in resolution. Morphologic and physiologic factors associated with the maturation of the murine intestinal tract at 2 to 3 weeks of age are most significant in the resolution of rotavirus infection and the development of resistance to disease.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD