A gastrointestinal rotavirus infection mouse model for immune modulation studies

Virol J. 2011 Mar 8:8:109. doi: 10.1186/1743-422X-8-109.

Abstract

Background: Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R®) could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection.

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Cell Line
  • Diarrhea / immunology*
  • Diarrhea / virology
  • Disease Models, Animal*
  • Gastrointestinal Tract / immunology*
  • Gastrointestinal Tract / virology
  • Humans
  • Mice*
  • Mice, Inbred BALB C
  • Rotavirus / immunology
  • Rotavirus / physiology*
  • Rotavirus Infections / immunology*
  • Rotavirus Infections / virology

Substances

  • Antibodies, Viral