instance, rotavirus NSP4 acts as an enterotoxin that induces diarrhea in mice in the absence of rotavirus replication [5] . NSP4 affects Ca 2+ and electrolyte homeostasis in an auto-and paracrine fashion in both rotavirus-infected and uninfected intestinal cells [41] . NSP4 increases Ca 2+ permeability of the ER and plasma membrane, resulting in an increased Ca 2+ concentration in the cytosol ([Ca 2+ ] cyt ), causing derailment of numerous Ca 2+ -dependent cellular processes [40] . In uninfected enterocytes and crypt cells this rise in [Ca 2+ ] cyt is induced by binding of exogenous NSP4 to an apical receptor that modulates the PLC-IP 3 pathway [16] . The higher [Ca 2+ ] cyt triggers laminal secretion of peptides and amines by uninfected enterocytes, and luminal Cland H 2 O secretion by crypt cells [28, 39] . In infected enterocytes, the rise in [Ca 2+ ] cyt is believed to be independent of PLC modulation [41] , and this rise perturbs cytoskeleton and tight junction integrity, which ultimately leads to cell lysis [9, 10, 26, 37] .