Rotavirus non-structural protein 4 (NSP4)

Rotavirus non-structural protein 4 (NSP4) is a multifunctional transmembrane glycoprotein that serves as the first identified viral enterotoxin (Ball et al., 1996, Science). It is primarily localized to the endoplasmic reticulum (ER) of infected intestinal epithelial cells, where it acts as a viroporin to release calcium into the cytoplasm (Hyser et al., 2010, Journal of Virology). This elevation of intracellular calcium triggers a signaling cascade involving phospholipase C and the enteric nervous system, ultimately leading to the activation of calcium-activated chloride channels and the induction of secretory diarrhea (Morris et al., 1999, American Journal of Physiology). Additionally, NSP4 is vital for viral replication, serving as a receptor for the budding of double-layered particles into the ER lumen to acquire their outer capsid (Taylor et al., 1993, Journal of Virology). Given its dual role in viral assembly and pathogenesis, NSP4 is a significant target for therapeutic intervention, including the development of small-molecule inhibitors and neutralizing antibodies (Vanden Berghe et al., 2006, Journal of Virology).

Other names

Non-structural glycoprotein NSP4VP10Rotavirus enterotoxinNS28

NSP4 functions as a viral enterotoxin that induces a phospholipase C-dependent increase in cytosolic calcium, leading to the activation of calcium-activated chloride channels and subsequent secretory diarrhea.