Genetic characterization of the rotavirus nonstructural protein, NSP4

The rotavirus nonstructural protein NSP4 plays a role in viral assembly by acting as an intracellular receptor for single-shelled particles and assisting in the translocation of these particles across the endoplasmic reticulum. Recently, NSP4 has been implicated in rotavirus virulence and is thought to act as an enterotoxin which triggers chloride secretion by a calcium-dependent signal transduction pathway. Limited sequence analysis of NSP4 shows a well-conserved protein. To define the extent of sequence variation in the gene coding for NSP4, we have sequenced this gene from nine human rotavirus strains. These data and the analysis of additional human strains and various animal rotaviruses (bovine, simian, equine, and porcine) by Northern blot hybridization suggested that three NSP4 genotypes were present among rotavirus strains. A correlation between NSP4 genotype and VP6 subgroup was also implied. Two different NSP4 genes (which encoded distinct types of NSP4 proteins) were found among standard human rotaviruses and in strains circulating in the local community and these showed homology to cognate genes in some animal strains.