Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate
Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate
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DOI：
10.1038/nm0897-866
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发表时间：
1997-08-01
期刊：
影响因子：
82.9
通讯作者：
Marks, RM
中科院分区：
文献类型：
--
作者：
Chen, YP;Maguire, T;Marks, RM
登革病毒是一种人类病原体，它作为一种日益重要的公共卫生威胁再次出现。我们发现登革病毒包膜蛋白用于结合靶细胞的细胞受体是一种高度硫酸化的硫酸乙酰肝素类型。肝素、高度硫酸化的硫酸乙酰肝素以及多磺酸盐药物苏拉明有效地阻止了登革病毒对靶细胞的感染，这表明包膜蛋白 - 靶细胞受体的相互作用是感染性的关键决定因素。登革病毒包膜蛋白序列在羧基末端包含两个假定的糖胺聚糖结合基序；第一个可以进行结构建模，并形成一个由碱性氨基酸组成的不寻常的延伸结合表面。在其他黄病毒科的包膜蛋白中也发现了类似的基序。开发抑制靶细胞结合的药物可能是治疗黄病毒感染的一种有效策略。
Dengue virus is a human pathogen that has reemerged as an increasingly important public health threat. We found that the cellular receptor utilized by dengue envelope protein to bind to target cells is a highly sulfated type of heparan sulfate. Heparin, highly sulfated heparan sulfate, and the polysulfonate pharmaceutical Suramin effectively prevented dengue virus infection of target cells, indicating that the envelope protein-target cell receptor Interaction is a critical determinant of infectivity. The dengue envelope protein sequence includes two putative glycosaminoglycan-binding motifs at the carboxy terminus; the first could be structurally modeled and formed an unusual extended binding surface of basic amino acids. Similar motifs were also identified in the envelope proteins of other flaviviridae. Developing pharmaceuticals that inhibit target cell binding may be an effective strategy for treating flavivirus infections.