Differential Use of the C-Type Lectins L-SIGN and DC-SIGN for Phlebovirus Endocytosis
Differential Use of the C-Type Lectins L-SIGN and DC-SIGN for Phlebovirus Endocytosis
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DOI：
10.1111/tra.12393
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发表时间：
2016-06-01
期刊：
影响因子：
4.5
通讯作者：
Lozach, Pierre-Yves
中科院分区：
文献类型：
--
作者：
Leger, Psylvia;Tetard, Marilou;Lozach, Pierre-Yves
布尼亚病毒对全球人类和牲畜的威胁日益严重。这些新出现的病原体感染细胞所使用的受体、细胞因子和内吞途径在很大程度上仍未被识别，并且特征很差。DC-SIGN是一种在真皮树突状细胞上高度表达的C型凝集素，已发现其充当许多静脉病毒（布尼亚病毒科）的真实进入受体，包括裂谷热病毒（RVFV）、托斯卡纳病毒（TOSV）和乌库涅米病毒（UUKV）。我们发现这些白蛉病毒可以利用另一种C型凝集素L-SIGN进行感染。L-SIGN与DC-SIGN具有77%的序列同源性，并在肝窦内皮细胞上表达。L-SIGN是UUKV结合所必需的，但不是病毒内化所必需的。一个内吞缺陷突变体的L-SIGN仍然能够介导病毒的摄取和感染，表明L-SIGN作为一个附着受体的静脉病毒，而不是内吞受体。我们的研究结果指出了一个根本的区别，在使用C型凝集素L-SIGN和DC-SIGN的UUKV进入细胞，虽然这两种蛋白质是密切相关的分子结构和生物学功能。这项研究揭示了白蛉病毒靶向肝脏的分子机制，也突出了病毒-受体相互作用的复杂性。
Bunyaviruses represent a growing threat to humans and livestock globally. The receptors, cellular factors and endocytic pathways used by these emerging pathogens to infect cells remain largely unidentified and poorly characterized. DC-SIGN is a C-type lectin highly expressed on dermal dendritic cells that has been found to act as an authentic entry receptor for many phleboviruses (Bunyaviridae), including Rift Valley fever virus (RVFV), Toscana virus (TOSV) and Uukuniemi virus (UUKV). We found that these phleboviruses can exploit another C-type lectin, L-SIGN, for infection. L-SIGN shares 77% sequence homology with DC-SIGN and is expressed on liver sinusoidal endothelial cells. L-SIGN is required for UUKV binding but not for virus internalization. An endocytosis-defective mutant of L-SIGN was still able to mediate virus uptake and infection, indicating that L-SIGN acts as an attachment receptor for phleboviruses rather than an endocytic receptor. Our results point out a fundamental difference in the use of the C-type lectins L-SIGN and DC-SIGN by UUKV to enter cells, although both proteins are closely related in terms of molecular structure and biological function. This study sheds new light on the molecular mechanisms by which phleboviruses target the liver and also highlights the added complexity in virus-receptor interactions beyond attachment.