Rotavirus nonstructural protein 4 (NSP4)-viral enterotoxin with multiple roles in pathogenesis of diarrhoea in children

Abstract

Nonstructural protein 4 (NSP4) of Rotavirus has been designated as the first viral enterotoxin. Its role in viral replication is already well known. Intensive research over the past decade has shown the involvement of this protein in many cellular activities both in 'expressed' as well as 'secreted' form. It is responsible for increased intracellular calcium levels in the infected cell leading to a cascade of events which involve phospholipase C mediated secretion of Chloride ions. NSP4 also inhibits intestinal disaccharidases and sodium glucose symporter (SGLT1) so that complex sugars are retained resulting in malabsorption. It also alters actin in the villi resulting in their flattening and overall decreased absorptive area. NSP4 is associated with extracellular proteins and is hypothesized to have paracrine effects on neighbouring cells. Recent research has found it to be an activator of enteric nervous system too. All these factors contribute to the pathogenesis of diarrhoea which looks multifactorial and certainly very different from the bacterial toxin mediated diarrhoeas of E. coli and V. cholerae. We still don't have the final word on this intriguing protein which is now a potential candidate for a vaccine against rotavirus. The aim of this review is to put forward the salient features of the research done to elucidate the functions of NSP4.