Receptor binding specificity of recent human H3N2 influenza viruses
Receptor binding specificity of recent human H3N2 influenza viruses
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DOI：
10.1186/1743-422x-4-42
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发表时间：
2007-05-09
期刊：
影响因子：
4.8
通讯作者：
Air, Gillian M.
中科院分区：
文献类型：
--
作者：
Kumari, Kshama;Gulati, Shelly;Air, Gillian M.
背景：已知人类流感病毒与连接半乳糖的α2-6的唾液酸结合，但尚未系统地检查该连接之外的结合特异性。 H3N2 人类流感分离株在 20 世纪 90 年代失去了与鸡红细胞的结合，但自 2003 年以来分离的病毒重新获得了凝集鸡红细胞的能力。我们研究了结合的特异性、最近病毒的血凝素序列的变化以及唾液酸在生产性感染中的作用。结果：凝集或不凝集鸡红细胞的病毒与 264 个寡糖的聚糖阵列表现出相同的结合，仅与 α 2-6-唾液酸糖的子集结合。我们发现血凝素中的氨基酸变化似乎与鸡红细胞结合相关，但通过诱变测试时没有效果。 Sf-9细胞上表达的重组血凝素与鸡红细胞结合，但释放的重组杆状病毒仅凝集人红细胞。类似地，不凝集鸡红细胞的分离物显示鸡红细胞对受感染的 MDCK 细胞的血吸着。我们认为鸡红细胞与细胞表面血凝素结合但不与病毒粒子结合是由于细胞表面上更有利的血凝素密度。我们研究了针对 α 2-6 唾液酸寡糖的特异性病毒是否表现出差异性地进入具有不同比例的 α 2-6 和 α 2-3 唾液酸的细胞，包括具有高水平 α 2-6 唾液酸的人 A549 和 HeLa 细胞，以及仅具有 α 2-3 唾液酸的 CHO 细胞。我们发现病毒进入所有测试的细胞类型并合成位于细胞核的病毒核蛋白和转运到细胞表面的血凝素，但感染性后代病毒仅从 MDCK 细胞中释放。结论：鸡红细胞的凝集与聚糖阵列上任何寡糖的结合改变无关，可能是由于血凝素密度增加而导致亲和力增加，而不是亲和力增加。 α 2-6 唾液酸的缺乏并不能保护细胞免受流感感染，细胞表面存在高水平的 α 2-6-唾液酸也不能保证具有 α 2-6 受体特异性的病毒的高效复制。
Background: Human influenza viruses are known to bind to sialic acid linked alpha 2-6 to galactose, but the binding specificity beyond that linkage has not been systematically examined. H3N2 human influenza isolates lost binding to chicken red cells in the 1990s but viruses isolated since 2003 have re-acquired the ability to agglutinate chicken erythrocytes. We have investigated specificity of binding, changes in hemagglutinin sequence of the recent viruses and the role of sialic acid in productive infection.Results: Viruses that agglutinate, or do not agglutinate, chicken red cells show identical binding to a Glycan Array of 264 oligosaccharides, binding exclusively to a subset of alpha 2-6-sialylsaccharides. We identified an amino acid change in hemagglutinin that seemed to correlate with chicken red cell binding but when tested by mutagenesis there was no effect. Recombinant hemagglutinins expressed on Sf-9 cells bound chicken red cells but the released recombinant baculoviruses agglutinated only human red cells. Similarly, an isolate that does not agglutinate chicken red cells show hemadsorption of chicken red cells to infected MDCK cells. We suggest that binding of chicken red cells to cell surface hemagglutinin but not to virions is due to a more favorable hemagglutinin density on the cell surface. We investigated whether a virus specific for alpha 2-6 sialyloligosaccharides shows differential entry into cells that have varying proportions of alpha 2-6 and alpha 2-3 sialic acids, including human A549 and HeLa cells with high levels of alpha 2-6 sialic acid, and CHO cells that have only alpha 2-3 sialic acid. We found that the virus enters all cell types tested and synthesizes viral nucleoprotein, localized in the nucleus, and hemagglutinin, transported to the cell surface, but infectious progeny viruses were released only from MDCK cells.Conclusion: Agglutination of chicken red cells does not correlate with altered binding to any oligosaccharide on the Glycan Array, and may result from increased avidity due to density of hemagglutinin and not increased affinity. Absence of alpha 2-6 sialic acid does not protect a cell from influenza infection and the presence of high levels of alpha 2-6-sialic acids on a cell surface does not guarantee productive replication of a virus with alpha 2-6 receptor specificity.