Age-Dependent Diarrhea Induced by a Rotaviral Nonstructural Glycoprotein

TLDR

NSP4 is an intracellular receptor that mediates acquisition of a transient membrane envelope during subviral particle budding into the endoplasmic reticulum. NSP4 and its 114–135 peptide induce age‑, dose‑, and specificity‑dependent diarrhea in young mice by elevating intracellular calcium and stimulating chloride secretion through a calcium‑dependent signaling pathway, acting as a viral enterotoxin.

Abstract

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.