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. 1984;29(11):1028–1035. doi: 10.1007/BF01311255

Pathogenesis of rotavirus-induced diarrhea

Preliminary studies in miniature swine piglet

David Y Graham 1,2,✉, Jeffrey W Sackman 1,2, Mary K Estes 1,2
PMCID: PMC7088308  PMID: 6489082

Abstract

The pathogenesis of diarrhea caused by rotavirus infection was studied in miniature swine piglets. The animals were inoculated orally with 2×107 plaque-forming units of porcine rotavirus (OSU strain). During the height of diarrhea, intestinal function was investigated byin vivo perfusion of a 30-cm segment of proximal jejunum and a 30-cm segment of distal ileum. Absorption of Na+ and water decreased and 3-O-methylglucose transport was markedly reduced,P<0.01 compared to control animals. Mucosal lactase and sucrase levels were depressed in both the jejunum and ileum,P<0.001. Na+, K+-ATPase activity was significantly depressed only in the ileum,P<0.001. These changes were associated with a marked reduction in villous height, suggesting that the diarrhea could be an osmotic diarrhea due to nutrient (carbohydrate) malabsorption. Fresh stool samples were obtained and analyzed immediately for NA+,K+, osmolarity, glucose, and lactose; the osmotic gap was also determined. Stool osmolarity continually increased from 248±20 mosm/liter prior to inoculation to 348±20 mosm/liter at 75±1 hr postinoculation (P<0.005); the majority of the fecal osmotic gap could be accounted for by the amount of lactose present in the stools. Stool sodium increased from 34±6 mM prior to inoculation to a maximum of 65±4 mM at 53±1 hr postinoculation,P<0.001. There was no significant change in potassium concentration. The present investigation suggests that rotavirus-induced diarrhea is due to virus destruction of enterocytes lining the intestinal villi, thus reducing the mucosal surface area and important digestive enzymes. This destruction leads to an osmotic diarrhea due to nutrient (primarily carbohydrate) malabsorption. A possible contributing role of unopposed secretion from the crypt cannot be excluded from this study.

Keywords: Lactase, Miniature Swine, Villous Height, Fresh Stool, Osmotic Diarrhea

Footnotes

This work was supported by the Veterans Administration, and by grants from the USDA-ARS Children's Nutrition Research Center, Baylor College of Medicine, by a grant R808333-01 from the Environmental Protection Agency, and from Vicks Health Care Division of Richardson-Vicks, Inc. (Mount Vernon, New York).

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