Modulation of enterotoxin binding and function in vitro and in vivo.

The use of the nontoxic B subunits of cholera and Escherichia coli enterotoxins in vitro and in vivo led to a decrease in toxin binding to target cells and a decrease in toxin-induced effects (i.e., morphological effects, adenylate cyclase activation, and fluid secretion). The reduction in toxin binding involves a process of down-regulation of cellular receptors for the toxin and not toxin occupancy of receptors. The extent of inhibition was dependent on the amount of B subunit used and on the duration of time after its use. Thus, in vivo exposure to a single bolus of B subunit was sufficient to block toxin binding and activity for up to 18 h. Because the B subunit binds extensively to the esophagus and the stomach, peroral administration will require a preparation that allows the subunit to reach the small bowel in a protected form. Our data provide a rationale for using B subunit therapy for short-term protection against the effects of enterotoxins, before the development of an immune response.

Encephalomyocarditis virus can bind to and transfect non-permissive cells.

Mouse embryo fibroblasts and mouse adrenal tumor cells support the replication of encephalomyocarditis (EMC) virus, whereas rat glial and rat hepatoma cells are non-permissive. These differences in susceptibility were not due to the lack of virus attachment to rat cells. The findings that rat cells could be transfected with RNA derived from EMC virus indicates that the block in viral replication in these cells occurs at some point between attachment and uncoating of virus, probably at the level of uncoating.