Rotavirus infection impairs intestinal brush-border membrane Na(+)-solute cotransport activities in young rabbits.
The mechanism of rotavirus diarrhea was investigated by infecting young, specific pathogen-free, New Zealand rabbits with a lapine rotavirus, strain La/RR510. With 4-wk-old animals, virus shedding into the intestinal lumen peaked at 72 h postinfection (hpi), and a mild, watery diarrhea appeared at 124 hpi. No intestinal lesions were seen up to 144 hpi, indicating that diarrhea does not follow mucosal damage but can precede it, as if cell dysfunction were the cause, not the consequence, of the histological lesions. Kinetic analyses with brush-border membrane vesicles isolated from infected rabbits revealed strong inhibition of both Na(+)-D-glucose (SGLT1) and Na(+)-L-leucine symport activities. For both symporters, only maximum velocity decreased with time. The density of phlorizin-binding sites and SGLT1 protein antigen in the membrane remained unaffected, indicating that the virus effect on this symporter is direct. Because SGLT1 supports water reabsorption under physiological conditions, the mechanism of rotavirus diarrhea may involve a generalized inhibition of Na(+)-solute symport systems, hence, of water reabsorption. Massive water loss through the intestine may eventually overwhelm the capacity of the organ for water reabsorption, thereby helping the diarrhea to get established.
Halaihel
N
N
Institut National de la Santé et de la Recherche Médicale, Unité 510, Faculté de Pharmacie, Université de Paris XI, 92296 Châtenay-Malabry, France.
Liévin
V
V
Alvarado
F
F
Vasseur
M
M
D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D003967:Diarrhea / Q000378:metabolism; D005947:Glucose / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism* / Q000821:virology*; D007700:Kinetics; D007930:Leucine / Q000493:pharmacokinetics; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism / Q000821:virology; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000378:metabolism*; D011817:Rabbits; D012400:Rotavirus Infections / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1; D014867:Water / Q000378:metabolism
D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D051269:Sodium-Glucose Transporter 1; D014867:Water; D012964:Sodium; D007930:Leucine; D005947:Glucose