Rotaviruses are the leading causes of severe and life-threatening gastroenteritis in children and animals. Children are susceptible to symptomatic infection between the ages of 6 months to 2 years. The pathogenesis of the diarrhea remains poorly understood but it has been attributed to changes in transepithelial fluid balance, malabsorption due to destruction of epithelial lining of bowel, and vacular damage and ischemia of villi. In the April 12, 96 issue of Science, Ball et al describe that the NSP4, a non-structural glycoprotein of rotavirus acts as a viral enterotoxin. This protein is an intracellular receptor that mediates the acquisition of a transient membrane envelope during the budding of the subviral particles into the endoplasmic reticulum. Purified NSP4 protein induced diarrhea in mice. The protein was shown to potentiate the chloride secretion by a calcium-dependent signalling pathway. In the same issue of Science, using a murine model and “backpack tumor” tranplants, Burns et al evaluated the protective effect of antibodies against VP4 (an outer capsid viral protein) and VP6 (a major inner capsid viral protein) in confering immunity against the infection by rotavirus. Only two non-neutralizaing immunoglobulin (IgA) antibodies to VP6 prevented primary and resolving chronic murine rotavirus infections. In addition, data were presented that showed that only when the antibody reached the basolateral side of the epithelium, the protective effect could be seen and the antibody presented to the luminal side of the epithelium was ineffective in rendering a similar immunity. These findings support the idea that the inactivation of the virus presumably occurs during transcytosis of secretory IgA.
Rotaviruses are the leading causes of severe and life-threatening gastroenteritis in children and animals. Children are susceptible to symptomatic infection between the ages of 6 months to 2 years. The pathogenesis of the diarrhea remains poorly understood but it has been attributed to changes in transepithelial fluid balance, malabsorption due to destruction of epithelial lining of bowel, and vacular damage and ischemia of villi. In the April 12, 96 issue of Science, Ball et al describe that the NSP4, a non-structural glycoprotein of rotavirus acts as a viral enterotoxin. This protein is an intracellular receptor that mediates the acquisition of a transient membrane envelope during the budding of the subviral particles into the endoplasmic reticulum. Purified NSP4 protein induced diarrhea in mice. The protein was shown to potentiate the chloride secretion by a calcium-dependent signalling pathway. In the same issue of Science, using a murine model and “backpack tumor” tranplants, Burns et al evaluated the protective effect of antibodies against VP4 (an outer capsid viral protein) and VP6 (a major inner capsid viral protein) in confering immunity against the infection by rotavirus. Only two non-neutralizaing immunoglobulin (IgA) antibodies to VP6 prevented primary and resolving chronic murine rotavirus infections. In addition, data were presented that showed that only when the antibody reached the basolateral side of the epithelium, the protective effect could be seen and the antibody presented to the luminal side of the epithelium was ineffective in rendering a similar immunity. These findings support the idea that the inactivation of the virus presumably occurs during transcytosis of secretory IgA.
