This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Halaihel, N.
Right arrow Articles by Vasseur, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Halaihel, N.
Right arrow Articles by Vasseur, M.

 Previous Article  |  Next Article 

Journal of Virology, October 2000, p. 9464-9470, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Direct Inhibitory Effect of Rotavirus NSP4(114-135) Peptide on the Na+-D-Glucose Symporter of Rabbit Intestinal Brush Border Membrane

Nabil Halaihel,1 Vanessa Liévin,1 Judith M. Ball,2 Mary K. Estes,3 Francisco Alvarado,1,dagger and Monique Vasseur1,*

Institut National de la Santé et de la Recherche Médicale, Unité 510, Faculté de Pharmacie, Université de Paris XI, 92296 Châtenay-Malabry, France1; Department of Pathobiology, Texas Veterinary Medical Center, Texas A&M University, College Station, Texas 77843-44672; and Division of Molecular Biology, Baylor College of Medicine, Texas Medical Center, Houston, Texas 770303

Received 31 March 2000/Accepted 27 July 2000

The direct effect of a rotavirus nonstructural glycoprotein, NSP4, and certain related peptides on the sodium-coupled transport of D-glucose and of L-leucine was studied by using intestinal brush border membrane vesicles isolated from young rabbits. Kinetic analyses revealed that the NSP4(114-135) peptide, which causes diarrhea in young rodents, is a specific, fully noncompetitive inhibitor of the Na+-D-glucose symporter (SGLT1). This interaction involves three peptide-binding sites per carrier unit. In contrast, the Norwalk virus NV(464-483) and mNSP4(131K) peptides, neither of which causes diarrhea, both behave inertly. The NSP4(114-135) and NV(464-483) peptides inhibited Na+-L-leucine symport about equally and partially via a different transport mechanism, in that Na+ behaves as a nonobligatory activator. The selective and strong inhibition caused by the NSP4(114-135) peptide on SGLT1 in vitro suggests that during rotavirus infection in vivo, NSP4 can be one effector directly causing SGLT1 inhibition. This effect, implying a concomitant inhibition of water reabsorption, is postulated to play a mechanistic role in the pathogenesis of rotavirus diarrhea.

* Corresponding author. Mailing address: Unité 510, INSERM, Faculté de Pharmacie, Université de Paris XI, 5, rue J.-B. Clément, 92296 Châtenay-Malabry, France. Phone: (33 1) 46 83 57 95. Fax: (33 1) 46 83 58 44. E-mail: monique.vasseur{at}cep.u-psud.fr.

dagger Present address: Departamento Bioquímica y Biologiá Molecular, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.

Journal of Virology, October 2000, p. 9464-9470, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Borghan, M. A., Mori, Y., El-Mahmoudy, A.-B., Ito, N., Sugiyama, M., Takewaki, T., Minamoto, N. (2007). Induction of nitric oxide synthase by rotavirus enterotoxin NSP4: implication for rotavirus pathogenicity. J. Gen. Virol. 88: 2064-2072 [Abstract] [Full Text]  
  • Parr, R. D., Storey, S. M., Mitchell, D. M., McIntosh, A. L., Zhou, M., Mir, K. D., Ball, J. M. (2006). The Rotavirus Enterotoxin NSP4 Directly Interacts with the Caveolar Structural Protein Caveolin-1. J. Virol. 80: 2842-2854 [Abstract] [Full Text]  
  • Kunzelmann, K., McMorran, B. (2004). First Encounter: How Pathogens Compromise Epithelial Transport. Physiology 19: 240-244 [Abstract] [Full Text]  
  • Ramig, R. F. (2004). Pathogenesis of Intestinal and Systemic Rotavirus Infection. J. Virol. 78: 10213-10220 [Full Text]  
  • Boshuizen, J. A., Rossen, J. W. A., Sitaram, C. K., Kimenai, F. F. P., Simons-Oosterhuis, Y., Laffeber, C., Buller, H. A., Einerhand, A. W. C. (2004). Rotavirus Enterotoxin NSP4 Binds to the Extracellular Matrix Proteins Laminin-{beta}3 and Fibronectin. J. Virol. 78: 10045-10053 [Abstract] [Full Text]  
  • Boshuizen, J. A., Reimerink, J. H. J., Korteland-van Male, A. M., van Ham, V. J. J., Koopmans, M. P. G., Buller, H. A., Dekker, J., Einerhand, A. W. C. (2003). Changes in Small Intestinal Homeostasis, Morphology, and Gene Expression during Rotavirus Infection of Infant Mice. J. Virol. 77: 13005-13016 [Abstract] [Full Text]  
  • Mori, Y., Borgan, M. A., Ito, N., Sugiyama, M., Minamoto, N. (2002). Diarrhea-Inducing Activity of Avian Rotavirus NSP4 Glycoproteins, Which Differ Greatly from Mammalian Rotavirus NSP4 Glycoproteins in Deduced Amino Acid Sequence, in Suckling Mice. J. Virol. 76: 5829-5834 [Abstract] [Full Text]  
  • Kunzelmann, K., Mall, M. (2002). Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease. Physiol. Rev. 82: 245-289 [Abstract] [Full Text]  
  • Ciarlet, M., Crawford, S. E., Estes, M. K. (2001). Differential Infection of Polarized Epithelial Cell Lines by Sialic Acid-Dependent and Sialic Acid-Independent Rotavirus Strains. J. Virol. 75: 11834-11850 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»