Rotavirus non-structural glycoprotein 4 (NSP4)

Rotavirus non-structural glycoprotein 4 (NSP4) is a multifunctional, 175-amino-acid, endoplasmic reticulum (ER)-residing transmembrane glycoprotein encoded by gene segment 10 of the rotavirus genome[2][5]. NSP4 functions as a viroporin, forming calcium-permeable ion channels that disrupt the host cell’s calcium homeostasis, a process essential for efficient viral replication and pathogenesis[4][6]. It is also the first described viral enterotoxin, contributing directly to rotavirus-induced secretory diarrhea by stimulating phospholipase C-dependent calcium signaling in intestinal cells through a secreted, proteolytically-processed form that binds cell surface integrins[2][4][5]. NSP4 participates in virus particle morphogenesis, particularly the budding of double-layered particles (DLPs) into the ER, and serves as an intracellular receptor for these particles[1][2]. In addition, NSP4 influences multiple aspects of host cell physiology, including induction of the unfolded protein response, disruption of plasma membrane integrity, inhibition of sodium and glucose absorption, and remodeling of the cytoskeleton[2][5]. Its structure features an N-terminal three-helical viroporin domain, a central cytoplasmic coiled-coil domain for multimerization, and a flexible C-terminal region for microtubule interaction[5]. Structural and functional flexibility enables it to exist in multiple oligomeric states within different subcellular compartments, allowing NSP4 to coordinate various steps in the rotavirus life cycle[3].

Other names

Rotavirus NSP4Non-structural glycoprotein 4Viroporin NSP4

Forms calcium-conducting ion channels (viroporin activity) in host endoplasmic reticulum; Functions as a viral enterotoxin by interacting with host integrin receptors and inducing phospholipase C activation and intracellular calcium release