Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses
Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses
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DOI：
10.1038/sj.embor.embor866
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发表时间：
2003-07-01
期刊：
影响因子：
7.7
通讯作者：
Desprès, P
中科院分区：
文献类型：
--
作者：
Navarro-Sanchez, E;Altmeyer, R;Desprès, P
登革热病毒（DV）是一种蚊媒黄病毒，可引起人类出血热。DV主要靶向被感染的蚊子媒介叮咬后的未成熟树突状细胞（DC）。在这里，我们分析了DV和人单核细胞衍生的DC在病毒进入水平上的相互作用。我们表明，DC特异性ICAM 3抓取非整联蛋白（DC-SIGN）分子，细胞表面，甘露糖特异性，C型凝集素，结合蚊子细胞衍生的DV，并允许病毒复制。通过抗DC-SIGN抗体和DC-SIGN的可溶性四聚体胞外域对病毒感染的抑制，获得了DC-SIGN参与DV感染的结论性证据。我们的数据表明，DC-SIGN功能作为DV结合凝集素通过与DV包膜糖蛋白相互作用。蚊子细胞衍生的DV可能对DC-SIGN表达细胞具有不同的感染性。我们认为，DC-SIGN的病毒包膜糖蛋白的差异使用可能占DV的免疫发病机制。
Dengue virus (DV) is a mosquito-borne flavivirus that causes haemorrhagic fever in humans. DV primarily targets immature dendritic cells (DCs) after a bite by an infected mosquito vector. Here, we analysed the interactions between DV and human-monocyte-derived DCs at the level of virus entry. We show that the DC-specific ICAM3-grabbing non-integrin (DC-SIGN) molecule, a cell-surface, mannose-specific, C-type lectin, binds mosquito-cell-derived DVs and allows viral replication. Conclusive evidence for the involvement of DC-SIGN in DV infection was obtained by the inhibition of viral infection by anti-DC-SIGN antibodies and by the soluble tetrameric ectodomain of DC-SIGN. Our data show that DC-SIGN functions as a DV-binding lectin by interacting with the DV envelope glycoprotein. Mosquito-cell-derived DVs may have differential infectivity for DC-SIGN-expressing cells. We suggest that the differential use of DC-SIGN by viral envelope glycoproteins may account for the immunopathogenesis of DVs.