Diversity of sugar chain recognition by hemagglutinin and transmission mechanism of influenza viruses

血凝素识别糖链的多样性及流感病毒的传播机制

• 批准号: 11670301
• 负责人: SUZUKI Takashi
• 金额: $ 2.37万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670301/
• 关键词: influenza Virus; Sialic acid; Host range; sulfatide; hemagglutinin; N-acetylnevramic acid; N-glycolylneramic acid

This project aims at explicating the role of hemagglutinin on the replication of influenza viruses and transmission of the viruses between the hosts.The results of the project are as follows.1. We tested the binding reactivity of human H3 influenza A viruses, which were isolated from 1968 to 1979, to sialylglycolipids containing different molecular species of terminal sialic acids. All human H3 viruses tested bound both Neu5Ac and Neu5Gc.2. We examined the relative abundance of Neu5Ac and Neu5Gc in the epithelial cells of horse trachea. More than 90 % of the sialic acid was Neu5Gc, while the remaining proportion was NeuAc. The major sialic acid-Galactose moiety present in horse tracheal epithelial cells is Neu5Gcα2.3Gal. We examined the requirement for the hemagglutinin for support of viral replication in horses, using viruses whose Has differ in receptor specificity. The results indicated that recognition of Neu5Gcα2,3Gal moiety is critical for viral replication in horses.3. The recognition of a glycoconjugate moiety possessing Neu5Gcα2,3Gal was associated with viral replication in duck intestine.4. Sulfatide binding site is localized in the sialic acid binding pocket of HA or the neighborhood of the pocket.

本项目旨在阐明血凝素在流感病毒复制和病毒在宿主间传播中的作用。我们测定了1968~1979年分离的人H3型甲型流感病毒与含有不同分子种类末端唾液酸的唾液酸糖脂的结合活性。所有测试的人类H3病毒都结合了Neu5Ac和Neu5Gc2。我们检测了马气管上皮细胞中Neu5Ac和Neu5Gc的相对丰度。唾液酸90%以上为Neu5Gc，其余为NeuAc。马气管上皮细胞中存在的主要唾液酸-半乳糖部分是Neu5Gcα2.3Gal.我们使用受体特异性不同的病毒，研究了支持病毒复制所需的血凝素。结果表明，Neu5Gcα2，3Gal部分的识别是病毒在马体内复制的关键。识别含有Neu5Gcα2，3Gal的糖基化部分与病毒在鸭肠道内的复制有关。硫脂结合部位定位于HA的唾液酸结合口袋或口袋附近。

项目成果

Tetsuya Furuike, Seiichi Aiba, Takashi Suzuki, Tadanobu Takahashi, Yasuo Suzuki, Kuriko Yamada, and Shin-Ichiro Nishimura: "Synthesis and anti-influenza virus activity of novel glycopolymers having triantennary oligosaccharide branches"J. Chem. Soc. Perki

Tetsuya Furuike、Seiichi Aiba、Takashi Suzuki、Tadanobu Takahashi、Yasuo Suzuki、Kuriko Yamada 和 Shin-Ichiro Nishimura：“具有三触角寡糖分支的新型糖聚合物的合成和抗流感病毒活性”J。

Kiyoshi Ikeda: "Synthesis of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid analogues modified at the C-4 and C-9 positions and their behaviour towards sialidase from influenza virus and pig liver membrane."Carbohydrate Research. 330. 31-41 (2001)

Kiyoshi Ikeda：“C-4 和 C-9 位点修饰的 2-脱氧-2,3-二脱氢-N-乙酰神经氨酸类似物的合成及其对流感病毒和猪肝膜唾液酸酶的行为。”碳水化合物研究。

Yasuo Suzuki: "Sialic acid species as a determinant of the host range of influenza A viruses."Journal of Virology. 74. 11825-11831 (2000)

Yasuo Suzuki：“唾液酸种类是甲型流感病毒宿主范围的决定因素。”病毒学杂志。

Darwyn Kobasa: "Amino acid residures contributing to the substrate specificity of the influenza A virus neuraminidase"J. Virol.. 73. 6743-6751 (1999)

Darwyn Kobasa：“氨基酸残基有助于甲型流感病毒神经氨酸酶的底物特异性”J。

Yasuhiro Hosaka: "Binding of influenza type A viruses to group B Streptococcus and haemagglutination by virus-bound bacteria"J. Electron Micrasc.. 49. 765-773 (2000)

Yasuhiro Hosaka：“甲型流感病毒与 B 族链球菌的结合以及病毒结合细菌的血凝作用”J。