Glycan analysis and influenza A virus infection of primary swine respiratory epithelial cells: the importance of NeuAc{alpha}2-6 glycans.
Glycan analysis and influenza A virus infection of primary swine respiratory epithelial cells: the importance of NeuAc{alpha}2-6 glycans.
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DOI：
10.1074/jbc.m110.115998
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发表时间：
2010-10-29
期刊：
影响因子：
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通讯作者：
Haslam SM
中科院分区：
文献类型：
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作者：
Bateman AC;Karamanska R;Busch MG;Dell A;Olsen CW;Haslam SM
为了更好地了解猪流感病毒感染，我们检测了猪原代呼吸道上皮细胞（SRECs，流感病毒在体内的主要靶细胞）作为模型系统。通过质谱分析SRECs的糖谱分析显示，SRECs具有多种终止于唾液酸或半乳糖α半乳糖的聚糖。在唾液化方面，α2-6连锁比α2-3丰富，NeuAc比NeuGc丰富。进行了病毒结合和感染实验，以确定流感病毒感染的功能重要聚糖，重点是最近出现的猪病毒。猪和人感染SRECs病毒导致不同的感染水平。对在北美猪群中广泛传播的高传染性“三重组”病毒（a /Swine/MN/593/99 (H3N2)）和从单头猪中分离的低传染性人类病毒（a /Swine/ONT/00130/97 (H3N2)）的聚糖微阵列分析表明，这两种病毒都只与含有NeuAcα2-6的聚糖结合，与唾液化聚乳糖胺和唾液化n -聚糖结合强烈。感染前用甘露糖胺唾液酸前体（改变NeuAc/NeuGc丰度）和特异性唾液酸酶治疗表明，测试的流感病毒优先利用NeuAcα2 - 6唾液酸化聚糖感染SRECs。我们的数据表明，neuac α2 - 6端聚乳糖胺和唾液化n -聚糖是流感病毒感染SRECs的重要决定因素。由于NeuAcα2-6聚乳胺聚糖在人流感病毒感染中发挥重要作用，这些受体成分在猪细胞病毒感染中的重要性，意味着病毒在人与猪之间的传播，以及猪可能成为新型人流感病毒的适应宿主。
To better understand influenza virus infection of pigs, we examined primary swine respiratory epithelial cells (SRECs, the primary target cells of influenza viruses in vivo), as a model system. Glycomic profiling of SRECs by mass spectrometry revealed a diverse range of glycans terminating in sialic acid or GalαGal. In terms of sialylation, α2–6 linkage was more abundant than α2–3, and NeuAc was more abundant than NeuGc. Virus binding and infection experiments were conducted to determine functionally important glycans for influenza virus infection, with a focus on recently emerged swine viruses. Infection of SRECs with swine and human viruses resulted in different infectivity levels. Glycan microarray analysis with a high infectivity “triple reassortant” virus ((A/Swine/MN/593/99 (H3N2)) that spread widely throughout the North American swine population and a lower infectivity human virus isolated from a single pig (A/Swine/ONT/00130/97 (H3N2)) showed that both viruses bound exclusively to glycans containing NeuAcα2–6, with strong binding to sialylated polylactosamine and sialylated N-glycans. Treatment with mannosamine precursors of sialic acid (to alter NeuAc/NeuGc abundances) and linkage-specific sialidases prior to infection indicated that the influenza viruses tested preferentially utilize NeuAcα2–6-sialylated glycans to infect SRECs. Our data indicate that NeuAcα2–6-terminated polylactosamine and sialylated N-glycans are important determinants for influenza viruses to infect SRECs. As NeuAcα2–6 polylactosamine glycans play major roles in human virus infection, the importance of these receptor components in virus infection of swine cells has implications for transmission of viruses between humans and pigs and for pigs as possible adaptation hosts of novel human influenza viruses.