INFLUENZA-VIRUS STRAINS SELECTIVELY RECOGNIZE SIALYLOLIGOSACCHARIDES ON HUMAN RESPIRATORY EPITHELIUM - THE ROLE OF THE HOST-CELL IN SELECTION OF HEMAGGLUTININ RECEPTOR SPECIFICITY
INFLUENZA-VIRUS STRAINS SELECTIVELY RECOGNIZE SIALYLOLIGOSACCHARIDES ON HUMAN RESPIRATORY EPITHELIUM - THE ROLE OF THE HOST-CELL IN SELECTION OF HEMAGGLUTININ RECEPTOR SPECIFICITY
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DOI：
10.1016/0168-1702(93)90056-s
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发表时间：
1993-08-01
期刊：
影响因子：
5
通讯作者：
BAUM, LG
中科院分区：
文献类型：
--
作者：
NELSON, J;COUCEIRO, SS;BAUM, LG
存在于人气管上皮表面的唾液酸低聚糖的补体已被认为是选择人甲型流感病毒血凝素受体特异性的重要因素。甲型流感病毒的人毒株优先识别带有SA α 2，6Gal序列的宿主细胞受体，该序列发现于纤毛气管上皮的表面上。荧光标记的H3人病毒株与人气管上皮细胞的顶面紧密结合，而荧光标记的受体变异株，其优先结合SA α 2，3Gal序列，几乎不与上皮细胞表面结合，主要定位于细胞内粘蛋白液滴。已知主要在SA α 2，3Gal键中含有唾液酸的人支气管粘蛋白的提取物是受体变体菌株与气管切片结合的有效抑制剂，而亲本菌株的结合不受粘蛋白存在的影响。人支气管粘蛋白也抑制受体变异株，但不是亲本病毒株，与衍生含有SA α 2，6Gal序列的人红细胞的结合。这些结果表明，呼吸道环境中存在的选择压力的组合导致了人甲型流感病毒株中血凝素受体特异性的进化，其优化了宿主细胞的识别、结合和感染。
The complement of sialyloligosaccharides present on the surface of human tracheal epithelium has been implicated as an important factor in the selection of hemagglutinin receptor specificity of human influenza A virus. Human strains of influenza A virus preferentially recognize host cell receptors bearing SAalpha2,6Gal sequences, a sequence which is found on the surface of ciliated tracheal epithelium. A fluorescently-labelled H3 human virus strain bound avidly to the apical surface of human tracheal epithelium, while a fluorescently-labelled receptor variant strain, which preferentially binds SAalpha2,3Gal sequences, showed little binding to the epithelial surface and localized primarily to intracellular mucin droplets. Extracts of human bronchial mucin, which is known to contain sialic acid primarily in the SAalpha2,3Gal linkage, was a potent inhibitor of the binding of the receptor variant strain to trachea sections, while the binding of the parent strain was unaffected by the presence of mucin. Human bronchial mucin also inhibited the binding of the receptor variant strains, but not the parent virus strains, to human erythrocytes derivatized to contain SAalpha2,6Gal sequences. These results suggest that a combination of selection pressures present in the respiratory tract environment have resulted in the evolution of a hemagglutinin receptor specificity in human influenza A virus strains which optimizes recognition of, binding to and infection of host cells.