ROTAVIRUS NONSTRUCTURAL PROTEIN 4 (NSP4) en-coded by gene 10 is the first described viral enterotoxin (7). Since the report of the NSP4 toxic activity, identification of other viral toxins has been described (6,125), which may account for enteric symptoms of simian and equine lentiviral infections. Numerous studies of NSP4 reveal the complexity of this multifunctional protein, some of which are described in this review. Taken as a whole, NSP4 is critical to rotaviral morphogenesis and pathogenesis, induces an effective immune response, and may aid in development of an efficacious rotavirus vaccine.

Enterotoxins are defined as toxins that stimulate net secretion in ligated intestinal segments in the absence of histological alterations and/or promote secretory currents as measured in Ussing chambers (122). In 1959, two groups independently showed that a culture filtrate of Vibrio cholerae induces profuse, watery diarrhea and identified the causative agent as a toxin (135). Since that time, numerous bacterial strains have been shown to produce a cholera-like enterotoxin, some of which include Es-