Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein.
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.
Ball
J M
JM
Division of Molecular Virology, Baylor College of Medicine, Houston, TX 77030, USA.
Tian
P
P
Zeng
C Q
CQ
Morris
A P
AP
Estes
M K
MK
D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003967:Diarrhea / Q000209:etiology* / Q000517:prevention & control / Q000821:virology; D004768:Enterotoxins / Q000633:toxicity*; D006023:Glycoproteins / Q000276:immunology / Q000633:toxicity*; D007106:Immune Sera / Q000008:administration & dosage; D007114:Immunization; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000633:toxicity; D011991:Receptors, Virus; D012401:Rotavirus / Q000472:pathogenicity*; D012400:Rotavirus Infections / Q000517:prevention & control / Q000821:virology*; D015398:Signal Transduction; D014118:Toxins, Biological; D017361:Viral Nonstructural Proteins / Q000276:immunology / Q000633:toxicity*
D002712:Chlorides; D004768:Enterotoxins; D006023:Glycoproteins; D007106:Immune Sera; C081369:NS28 protein, rotavirus; D010446:Peptide Fragments; D011991:Receptors, Virus; D014118:Toxins, Biological; D017361:Viral Nonstructural Proteins; D005576:Colforsin; D002217:Carbachol; D002118:Calcium