Enterotoxigenic activity of rotavirus NSP4

轮状病毒 NSP4 的肠毒素活性

• 批准号: 10670278
• 负责人: NAKAGOMI Toyoko
• 金额: $ 1.98万
• 依托单位: AKITA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670278/
• 关键词: rotavirus; nonstructural protein; gene analysis; enterotoxin; diarrhea; pathogenesis; ウイルス性下痢症; NSP4; マウスモデル

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.

轮状病毒被确定为幼龄动物以及婴儿和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，它们包含在三层衣壳中。基因片段10编码在轮状病毒形态发生中起重要作用的非结构蛋白4（NSP 4）。自从首次报道SA 11 NSP 4在乳鼠中具有肠促炎活性以来，NSP 4蛋白引起了更多的关注。然而，至今仍有争议，其是否真实的作用在牙周炎发病机制。来自A组轮状病毒株的31个NSP 4的系统发育分析允许鉴定四种不同的NSP 4等位基因; Wa、KUN、Au-1和EW等位基因，这意味着鼠NSP 4在遗传上不同于其他哺乳动物轮状病毒NSP 4。相比之下，A组轮状病毒NSP 4蛋白的基本结构是很保守的，根据Kyte和Doolittle算法，从几乎相同的疏水特性判断。我们推测，NSP 4蛋白的肠毒素活性依赖于一致的结构特征和在残基114-130处的保守的推定受体结合位点。我们的结论是，A组轮状病毒NSP 4有一个肠毒素活性时，给新生小鼠腹腔注射。我们还推测NSP 4蛋白在感染早期诱导腹泻中起重要作用。

项目成果

Horie Y,Nakagomi O,Nakagomi T,et al.: "Diarrhea induction by rotavirus NSP4 in the homologous mouse model system"Virology. 262. 398-407 (1999)

Horie Y、Nakagomi O、Nakagomi T 等人：“同源小鼠模型系统中轮状病毒 NSP4 诱导腹泻”病毒学。

Horie Y, Nagagomi O, Koshimura Y, Nakagomi T, Suzuki Y, Oka T, Sasaki S, Matsuda Y, Watanabe S: "Diarrhea induction by rotavirus NSP4 in the homologous mouse model system."Virology. 262. 398-407 (1999)

Horie Y、Nagagomi O、Koshimura Y、Nakagomi T、Suzuki Y、Oka T、Sasaki S、Matsuda Y、Watanabe S：“同源小鼠模型系统中轮状病毒 NSP4 诱导腹泻。”病毒学。

Horie Y, Nakagomi O, Koshimura Y, Nakagomi T, et al.: "Diarrhea induction by rotavirus NSP4 in the homologous mouse model system"Virology. 262. 398-407 (1999)

Horie Y、Nakagomi O、Koshimura Y、Nakagomi T 等：“同源小鼠模型系统中轮状病毒 NSP4 诱导腹泻”病毒学。