How do the rotavirus NSP4 and bacterial enterotoxins lead differently to diarrhea?
Rotavirus is the major cause of infantile gastroenteritis and each year causes 611,000 deaths worldwide. The virus infects the mature enterocytes of the villus tip of the small intestine and induces a watery diarrhea. Diarrhea can occur with no visible tissue damage and, conversely, the histological lesions can be asymptomatic. Rotavirus impairs activities of intestinal disaccharidases and Na+-solute symports coupled with water transport. Maldigestion of carbohydrates and their accumulation in the intestinal lumen as well as malabsorption of nutrients and a concomitant inhibition of water reabsorption can lead to a malabsorption component of diarrhea. Since the discovery of the NSP4 enterotoxin, diverse hypotheses have been proposed in favor of an additional secretion component in the pathogenesis of diarrhea. Rotavirus induces a moderate net chloride secretion at the onset of diarrhea, but the mechanisms appear to be quite different from those used by bacterial enterotoxins that cause pure secretory diarrhea. Rotavirus failed to stimulate Cl- secretion in crypt, whereas it stimulated Cl- reabsorption in villi, questioning, therefore, the origin of net Cl- secretion. A solution to this riddle was that intestinal villi do in fact secrete chloride as a result of rotavirus infection. Also, the overall chloride secretory response is regulated by a phospholipase C-dependent calcium signaling pathway induced by NSP4. However, the overall response is weak, suggesting that NSP4 may exert both secretory and subsequent anti-secretory actions, as did carbachol, hence limiting Cl- secretion. All these characteristics provide the means to make the necessary functional distinction between viral NSP4 and bacterial enterotoxins.
Lorrot
Mathie
M
Hôpital Robert Debré, Service de Pédiatrie Générale, Paris, F-75019, France. mathie.lorrot@rdb.ap-hop-paris.fr
Vasseur
Monique
M
D000042:Absorption; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D018938:Caco-2 Cells; D002712:Chlorides / Q000378:metabolism; D003967:Diarrhea / Q000382:microbiology / Q000503:physiopathology* / Q000821:virology; D004768:Enterotoxins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D012401:Rotavirus / Q000378:metabolism / Q000472:pathogenicity*; D014118:Toxins, Biological / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
D001427:Bacterial Toxins; D002712:Chlorides; D004768:Enterotoxins; D006023:Glycoproteins; C081369:NS28 protein, rotavirus; D014118:Toxins, Biological; D017361:Viral Nonstructural Proteins; D005947:Glucose