DC-SIGN as a Receptor for Phleboviruses
DC-SIGN as a Receptor for Phleboviruses
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DOI：
10.1016/j.chom.2011.06.007
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发表时间：
2011-07-21
影响因子：
30.3
通讯作者：
Helenius, Ari
中科院分区：
文献类型：
--
作者：
Lozach, Pierre-Yves;Kuehbacher, Andreas;Helenius, Ari
在自然传播过程中，布尼亚病毒通过节肢动物叮咬进入皮肤，皮肤树突状细胞（DC）是第一个遇到传入病毒的细胞。DC-SIGN是一种在真皮DC表面高度表达的C型凝集素。我们发现，几种节肢动物传播的静脉病毒（布尼亚病毒科），包括裂谷热和Uukuniemi病毒，利用DC-SIGN感染DC和其他DC-SIGN表达细胞。DC-SIGN通过与病毒糖蛋白上的高甘露糖N-聚糖相互作用直接结合病毒，并且是病毒内化和感染所必需的。在活细胞中，可以观察到病毒诱导的细胞表面DC-SIGN聚集。DC-SIGN的内吞缺陷突变体不能介导病毒摄取，表明DC-SIGN是附着和内吞所需的真实受体。内化后，病毒与DC-SIGN分离并运输至晚期内体。我们的研究提供了细胞表面病毒-受体相互作用的实时可视化，并建立了DC-SIGN作为静脉病毒进入受体。
During natural transmission, bunyaviruses are introduced into the skin through arthropod bites, and dermal dendritic cells (DCs) are the first to encounter incoming viruses. DC-SIGN is a C-type lectin highly expressed on the surface of dermal DCs. We found that several arthropod-borne phleboviruses (Bunyaviridae), including Rift Valley fever and Uukuniemi viruses, exploit DC-SIGN to infect DCs and other DC-SIGN-expressing cells. DC-SIGN binds the virus directly via interactions with high-mannose N-glycans on the viral glycoproteins and is required for virus internalization and infection. In live cells, virus-induced clustering of cell surface DC-SIGN could be visualized. An endocytosis-defective mutant of DC-SIGN was unable to mediate virus uptake, indicating that DC-SIGN is an authentic receptor required for both attachment and endocytosis. After internalization, viruses separated from DC-SIGN and underwent trafficking to late endosomes. Our study provides real-time visualization of virus-receptor interactions on the cell surface and establishes DC-SIGN as a phlebovirus entry receptor.