Binding of DC-SIGN to the Hemagglutinin of Influenza A Viruses Supports Virus Replication in DC-SIGN Expressing Cells

Binding of DC-SIGN to the Hemagglutinin of Influenza A Viruses Supports Virus Replication in DC-SIGN Expressing Cells
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DOI:
10.1371/journal.pone.0056164
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发表时间:
2013-02-12
期刊:
影响因子:
3.7
通讯作者:
Rimmelzwaan, Guus F.
Rimmelzwaan, Guus F.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hillaire, Marine L. B.;Nieuwkoop, Nella J.;Rimmelzwaan, Guus F.

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树突状细胞表达凝集素受体,如DC-SIGN,这使得这些细胞能够感知存在于各种细菌和病毒病原体上的聚糖。DC-SIGN与碳水化合物部分的相互作用诱导树突状细胞的成熟并促进病原体的内吞作用,这是这些专职抗原呈递细胞的重要特性。树突状细胞对病原体的摄取可能导致抗原的交叉呈递或这些细胞的感染,这最终导致引流淋巴结中病毒特异性T细胞的活化。关于DC-SIGN与甲型流感病毒的相互作用知之甚少。在这里,我们表明,在其血凝素中具有非功能性受体结合位点的病毒可以在表达DC-SIGN的细胞中复制。此外,在不存在作为甲型流感病毒受体的唾液酸的情况下,这些病毒在DC-SIGN表达细胞(包括人树突细胞)中复制。此外,DC-SIGN介导的感染的效率取决于病毒血凝素的糖基化程度。
Dendritic cells express lectins receptors, like DC-SIGN, which allow these cells to sense glycans that are present on various bacterial and viral pathogens. Interaction of DC-SIGN with carbohydrate moieties induces maturation of dendritic cells and promotes endocytosis of pathogens which is an important property of these professional antigen presenting cells. Uptake of pathogens by dendritic cells may lead to cross-presentation of antigens or infection of these cells, which ultimately results in activation of virus-specific T cells in draining lymph nodes. Little is known about the interaction of DC-SIGN with influenza A viruses. Here we show that a virus with a non-functional receptor binding site in its hemagglutinin, can replicate in cells expressing DC-SIGN. Also in the absence of sialic acids, which is the receptor for influenza A viruses, these viruses replicate in DC-SIGN expressing cells including human dendritic cells. Furthermore, the efficiency of DC-SIGN mediated infection is dependent on the extent of glycosylation of the viral hemagglutinin.