Humoral and cell-mediated immune responses in humans to the NSP4 enterotoxin of rotavirus

Rotavirus nonstructural protein NSP4 has recently been suggested to functio n as a viral enterotoxin and play a role in the pathophysioiogical mechanis m whereby rotaviruses induce diarrhea. The ability of rotavirus NSP4 to sti mulate a humoral immune response was examined in naturally infected childre n and adults, rotavirus vaccinated children, as well as a cellular immune r esponse in adults. In this study, 10 of 10 naturally infected children and 9 of 10 rotavirus-vaccinated children showed a weak humoral IgG immune resp onse to recombinant NSP4 (rNSP4) and/or a synthetic peptide corresponding t o residues 114-134 of NSP4. Modest serum IgG anti body responses were detec ted in 20 of 20 adults. A cellular immune response to rNSP4 and/or NSP4(114 -134) were detected in 8 of 10 adults measured either as a T-cell prolifera tive response (7 of 10), an increased production of IL-2 (6 of 10), or incr eased production of interferon-gamma (8 of 10). These results indicate that NSP4 induces a humoral immune response in humans and show for the first ti me that NSP4 stimulates a cellular immune response, possibly including cyto lytic T-cells. (C) 1999 Wiley-Liss, Inc.