STUDIES OF THE ROLE FOR NSP4 IN THE PATHOGENESIS OF HOMOLOGOUS MURINEROTAVIRUS DIARRHEA

A rotavirus (RV) nonstructural protein, NSP4, has recently been propos ed to function as an enterotoxin in the pathogenesis of RV diarrhea. T he role of NSP4 in the pathogenesis of RV diarrhea was examined by inf ecting cystic fibrosis transmembrane conductance regulator (CFTR) knoc kout mite with virulent murine RV and by comparing deduced amino acid sequences of RV gene 10 encoding NSP4 from three distinct sets of viru lent and tissue culture-adapted avirulent variant RVs. Homozygous CFTR (CFTR-/-) mice, which do not respond to any known intestinal secretag ogues, experienced diarrhea comparable to that in normal CFTR+/+ Litte rmates after RV challenge. Comparison of amino acid sequences of NSP4 from virulent and attenuated pairs of RVs failed to show consistent or significant changes. Together, these data suggest that enterotoxigeni c properties of RV NSP4 are not critical in the pathogenesis of murine RV diarrhea and that attenuation of murine RVs is not usually mediate d by mutations in the gene encoding NSP4.