A gastrointestinal rotavirus infection mouse model for immune modulation studies

BALB/c mice were treated by gavage once daily with Gastrogard-R？ from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV) at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM) virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH) responses were also measured.Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R？ were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R？. Mice receiving Gastrogard-R？ however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected.Preventing RRV-induced diarrhea by Gastrogard-R？ early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection.Rotavirus is one of the leading causes of severe dehydrating diarrhea in children under the age of five and causes the deaths of >600,000 children annually [1]. Rotaviruses, belonging to a genus of double-stranded RNA viruses in the family Reoviridae, infect the mature villus epithelial cells of the small intestine, often leading to fever, vomiting, and diarrhea in children. Current treatment is non-specific and consists mainly of oral rehydration therapy to prevent dehydration. Two live-attenuated vaccines have been licensed recently and ha