Enterotoxigenic activity of rotavirus NSP4

轮状病毒被确定为幼小动物以及婴幼儿严重腹泻的重要原因。轮状病毒基因组由11段双链RNA组成，这些片段包含在一个三层衣壳内。基因片段10编码非结构蛋白4(NSP4)，在轮状病毒的形态发生中起重要作用。自从首次报道SA11 nsp4在哺乳小鼠中具有肠道毒素活性以来，nsp4蛋白引起了更多的关注。然而，关于其在腹泻发病机制中的真正作用，至今仍存在争议。通过对A组轮状病毒31株NSP4的系统发育分析，确定了4个不同的NSP4等位基因：WA、Kun、AU-1和EW，这意味着小鼠的NSP4与其他哺乳动物轮状病毒NSP4在基因上是不同的。相比之下，A组轮状病毒nsp4蛋白的基本结构被很好地保守，根据Kyte和Doolitle算法得到的疏水图谱几乎相同。我们推测，NSP4蛋白的肠毒素活性依赖于其一致的结构特征和保守的114-130残基上假定的受体结合部位。我们认为，A组轮状病毒NSP4对新生小鼠具有一定的促肠毒素作用。我们还推测，NSP4蛋白在感染早期引起腹泻中起重要作用。

Rotaviruses are established as an important cause of severe diarrhea in young animals as well as infants and young children. The rotavirus genome consists of 11 segments of double-stranded RNA that are contained within a triple-layered capsid. Gene segment 10 encodes nonstructural protein 4 (NSP4) which plays an important role in rotavirus morphogenesis. The NSP4 protein has captured much greater attention since it was eported for the first time that SA11 NSP4 has an enterotoxigenic activity in suckling mice. However, controversy continues to date whether its real role in diarrheal pathogenesis. The phylogenetic analysis for 31 NSP4s from the group A rotavirus strains allowed identification of the four distinct NSP4 alleles ; the Wa, KUN, AU-1, and EW alleles, meaning that murine NSP4s are genetically different from other mammalian rotavirus NSP4s. By contrast, the basic structure of the group A rotavirus NSP4 protein was well conserved judging from the almost identical hydrophobic profiles according to the Kyte and Doolittle algorithm. We speculate that the enterotoxigenic activity of the NSP4 protein is dependent on the consistent structural features and the well conserved putative receptor binding site at residues 114-130. We conclude that group A rotavirus NSP4 has an eterotoxigenic activity when given intraperitoneally into neonatal mice. We also speculate that the NSP4 protein plays an important role in inducing diarrhea at the early stage of infection.