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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Glycans on influenza hemagglutinin affect receptor binding and immune response
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Glycans on influenza hemagglutinin affect receptor binding and immune response

机译：流感血细胞凝集素上的聚糖影响受体结合和免疫反应

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摘要

Recent cases of avian influenza H5N1 and the swine-origin 2009 H1N1 have caused a great concern that a global disaster like the 1918 influenza pandemic may occur again. Viral transmission begins with a critical interaction between hemagglutinin (HA) glycoprotein, which is on the viral coat of influenza, and sialic acid (SA) containing glycans, which are on the host cell surface. To elucidate the role of HA glycosylation in this important interaction, various defined HA gly-coforms were prepared, and their binding affinity and specificity were studied by using a synthetic SA microarray. Truncation of the N-glycan structures on HA increased SA binding affinities while decreasing specificity toward disparate SA ligands. The contribution of each monosaccharide and sulfate group within SA ligand structures to HA binding energy was quantitatively dissected. It was found that the sulfate group adds nearly 100-fold (2.04 kcal/mol) in binding energy to fully glycosylated HA, and so does the biantennary glycan to the monoglycosylated HA glycoform. Antibodies raised against HA protein bearing only a single N-linked GlcNAc at each glycosylation site showed better binding affinity and neutralization activity against influenza subtypes than the fully glycosylated HAs elicited. Thus, removal of structurally nonessential glycans on viral surface glycop-roteins may be a very effective and general approach for vaccine design against influenza and other human viruses.
机译：最近发生的禽流感H5N1和源自猪的2009 H1N1病例引起了人们的极大关注，即可能再次发生像1918年流感大流行这样的全球性灾难。病毒传播始于流感病毒衣壳上的血凝素（HA）糖蛋白与宿主细胞表面上的含有唾液酸的聚糖之间的关键相互作用。为了阐明HA糖基化在这一重要相互作用中的作用，制备了各种定义的HA gly-coform，并使用合成的SA微阵列研究了它们的结合亲和力和特异性。 HA上N聚糖结构的截断增加了SA结合亲和力，同时降低了对不同SA配体的特异性。定量分析了SA配体结构中每个单糖和硫酸根基团对HA结合能的贡献。发现硫酸根基团对完全糖基化的HA增加了近100倍的结合能（2.04 kcal / mol），双触角聚糖也对单糖基化的HA糖型增加了100倍。产生的针对HA蛋白的抗体在每个糖基化位点仅带有一个N-连接的GlcNAc，与引发的完全糖基化HA相比，具有更好的结合亲和力和中和活性。因此，去除病毒表面糖蛋白上的结构上不必要的聚糖可能是针对流感和其他人类病毒的疫苗设计的非常有效和通用的方法。

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  • 作者

    Cheng-Chi Wang; Juine-Ruey Chen; Yung-Chieh Tseng; Che-Hsiung Hsu; Yu-Fu Hung; Shih-Wei Chen; Chin-Mei Chen; Kay-Hooi Khoo; Ting-Jen Cheng; Yih-Shyun E. Cheng; Jia-Tsrong Jan; Chung-Yi Wu; Che Ma; Chi-Huey Wong;

  • 作者单位

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan lnstitute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program Academia Sinica, Taipei 115, Taiwan Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

    Institute of Biological Chemistry,Academia Sinica, Taipei 115, Taiwan;

    Institute of Biological Chemistry,Academia Sinica, Taipei 115, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    flu vaccine; glycan binding; glycosylation;

    机译：流感疫苗;聚糖结合糖基化;

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