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Science 5 April 1996:
Vol. 272. no. 5258, pp. 101 - 104
DOI: 10.1126/science.272.5258.101
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Reports

Age-Dependent Diarrhea Induced by a Rotaviral Nonstructural Glycoprotein

Judith M. Ball, Peng Tian, * Carl Q.-Y. Zeng, Andrew P. Morris, Mary K. Estes dagger

The rotavirus nonstructural glycoprotein NSP4 is an intracellular receptor that mediates the acquisition of a transient membrane envelope as subviral particles bud into the endoplasmic reticulum. NSP4 also causes an increase in intracellular calcium in insect cells. Purified NSP4 or a peptide corresponding to NSP4 residues 114 to 135 induced diarrhea in young (6 to 10 days old) CD1 mice. This disease response was age-dependent, dose-dependent, and specific. Electrophysiologic data from intestinal mucosa showed that the NSP4 114-135 peptide potentiates chloride secretion by a calcium-dependent signaling pathway. Diarrhea is induced when NSP4, acting as a viral enterotoxin, triggers a signal transduction pathway.

J. M. Ball, P. Tian, C. Q.-Y. Zeng, M. K. Estes, Division of Molecular Virology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
A. P. Morris, Department of Integrative Biology, University of Texas Health Science Center, Houston, TX 77030, USA.
* Present address: Howard Hughes Medical Institute and Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
dagger To whom correspondence should be addressed.


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J. Gen. Virol. 80, 1407-1415
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Malnutrition Modifies Pig Small Intestinal Inflammatory Responses to Rotavirus.
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N. Jourdan, J. P. Brunet, C. Sapin, A. Blais, J. Cotte-Laffitte, F. Forestier, A.-M. Quero, G. Trugnan, and A. L. Servin (1998)
J. Virol. 72, 7228-7236
   Abstract »    Full Text »    PDF »
Viral Determinants of Rotavirus Pathogenicity in Pigs: Evidence that the Fourth Gene of a Porcine Rotavirus Confers Diarrhea in the Homologous Host.
J. C. Bridger, G. I. Tauscher, and U. Desselberger (1998)
J. Virol. 72, 6929-6931
   Abstract »    Full Text »    PDF »
Mutations in Rotavirus Nonstructural Glycoprotein NSP4 Are Associated with Altered Virus Virulence.
M. Zhang, C. Q.-Y. Zeng, Y. Dong, J. M. Ball, L. J. Saif, A. P. Morris, and M. K. Estes (1998)
J. Virol. 72, 3666-3672
   Abstract »    Full Text »    PDF »
Carbohydrates Facilitate Correct Disulfide Bond Formation and Folding of Rotavirus VP7.
A. Mirazimi and L. Svensson (1998)
J. Virol. 72, 3887-3892
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Generation of a Mutant Infectious Bursal Disease Virus That Does Not Cause Bursal Lesions.
K. Yao, M. A. Goodwin, and V. N. Vakharia (1998)
J. Virol. 72, 2647-2654
   Abstract »    Full Text »    PDF »
Mycoplasma pulmonis Inhibits Electrogenic Ion Transport across Murine Tracheal Epithelial Cell Monolayers.
L. C. Lambert, H. Q. Trummell, A. Singh, G. H. Cassell, and R. J. Bridges (1998)
Infect. Immun. 66, 272-279
   Abstract »    Full Text »    PDF »
The rotavirus enterotoxin NSP4 mobilizes intracellular calcium in human intestinal cells by stimulating phospholipase C-mediated inositol 1,4,5-trisphosphate production.
Y. Dong, C. Q.-Y. Zeng, J. M. Ball, M. K. Estes, and A. P. Morris (1997)
PNAS 94, 3960-3965
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From the Cover: Influenza virus inhibits amiloride-sensitive Na+ channels in respiratory epithelia.
K. Kunzelmann, A. H. Beesley, N. J. King, G. Karupiah, J. A. Young, and D. I. Cook (2000)
PNAS 97, 10282-10287
   Abstract »    Full Text »    PDF »


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