Identification and characterization of carbohydrate molecules in mammalian cells recognized by dengue virus type 2
Identification and characterization of carbohydrate molecules in mammalian cells recognized by dengue virus type 2
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DOI：
10.1093/jb/mvj067
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发表时间：
2006-03-01
影响因子：
2.7
通讯作者：
Suzuki, Y
中科院分区：
文献类型：
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作者：
Aoki, C;Hidari, KIPJ;Suzuki, Y
细胞表面受体与病毒膜表面的囊膜糖蛋白（EGP）相互作用是登革病毒感染的起始步骤。为了了解该病原体的寄主范围、组织嗜性和毒力，阐明EGP与受体分子相互作用的分子机制至关重要。在这里，使用TLC/病毒结合试验，我们分离和表征了哺乳动物细胞表面上的糖分子，其被登革病毒2型（DEN 2）识别。免疫化学法测定其糖结构为新乳四糖神经酰胺（nLc（4）Cer）。这种鞘糖脂在易感细胞的细胞表面表达，如人红白血病K562和幼仓鼠肾BHK-21。DEN病毒的所有血清型，DEN 1至DEN 4，均与nLc（4）Cer反应，并且发现非还原性末端二糖残基Ga 1 β 1-4GlcNAc β 1-是DEN 2结合的关键决定因素。化学合成的衍生物携带多个nLc（4）的糖残基，但不是nLc（4）寡糖，抑制BHK-21细胞的DEN 2感染。这些结果强烈表明，多价nLc（4）寡糖可以作为一个竞争性抑制剂对登革2结合宿主细胞。
The interaction between cell surface receptors and the envelope glycoprotein (EGP) on the viral membrane surface is the initial step of Dengue virus infection. To understand the host range, tissue tropism, and virulence of this pathogen, it is critical to elucidate the molecular mechanisms of the interaction of EGP with receptor molecules. Here, using a TLC/virus-binding assay, we isolated and characterized a carbohydrate molecule on mammalian cell surfaces that is recognized by dengue virus type 2 (DEN2). Structural determination by immunochemical methods showed that the carbohydrate structure of the purified glycosphingolipid was neolactotetraosylceramide (nLc(4)Cer). This glycosphingolipid was expressed on the cell surface of susceptible cells, such as human erythroleukemia K562 and baby hamster kidney BHK-21. All serotypes of DEN viruses, DEN1 to DEN4, reacted with nLc(4)Cer, and the non-reducing terminal disaccharide residue Ga1 beta 1-4GlcNAc beta 1- was found to be a critical determinant for the binding of DEN2. Chemically synthesized derivatives carrying multiple carbohydrate residues of nLc(4), but not nLc(4) oligosaccharide, inhibited DEN2 infection of BHK-21 cells. These findings strongly suggested that multivalent nLc(4) oligosaccharide could act as a competitive inhibitor against the binding of DEN2 to the host cells.