Anti-NSP4 antibody can block rotavirus-induced diarrhea in mice

J Pediatr Gastroenterol Nutr. 2008 Apr;46(4):376-85. doi: 10.1097/MPG.0b013e3181661ae4.

Abstract

Background: Rotavirus infection is the most common cause of infectious diarrhea and gastroenteritis among children worldwide. The viral proteins (VP), especially VP4- and VP7-induced neutralizing antibodies, were considered to be critical in protective immunity to rotavirus disease. However, whether the antibody to rotavirus nonstructural protein 4 (NSP4) protects against rotavirus-induced diarrhea directly is not completely clear, especially for the protective time course.

Materials and methods: To obtain direct evidence, 12-day-old ICR mice were treated with NSP4 and entire rotavirus to induce diarrhea.

Results: Both NSP4 and rotavirus-treated mice developed diarrhea, which was accompanied by histological changes in the small intestine compared to age-matched control mice. Anti-NSP4 antibody demonstrated protection against both entire rotavirus-induced diarrhea and NSP4-induced diarrhea. The histological changes in the small intestinal were reversible. These data show that early intervention with anti-NSP4 antibody can prevent rotavirus-induced diarrhea in mice; late intervention with anti-NSP4 antibody could halt diarrhea progression in mice.

Conclusions: Our findings demonstrate for the first time that administration of anti-NSP4 antibody is effective both prior to and during the time course of rotavirus infection. These observations extend our knowledge of rotavirus infection and its therapeutic options.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Diarrhea / immunology*
  • Diarrhea / prevention & control
  • Disease Models, Animal
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Glycoproteins / immunology*
  • Intestine, Small / pathology
  • Mice
  • Mice, Inbred ICR
  • Random Allocation
  • Rotavirus / immunology*
  • Rotavirus Infections / immunology*
  • Rotavirus Infections / prevention & control
  • Specific Pathogen-Free Organisms
  • Toxins, Biological / immunology*
  • Viral Nonstructural Proteins / immunology*

Substances

  • Antibodies, Viral
  • Glycoproteins
  • NS28 protein, rotavirus
  • Toxins, Biological
  • Viral Nonstructural Proteins