Macrophage Receptors for Influenza A Virus: Role of the Macrophage Galactose-Type Lectin and Mannose Receptor in Viral Entry
Macrophage Receptors for Influenza A Virus: Role of the Macrophage Galactose-Type Lectin and Mannose Receptor in Viral Entry
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DOI：
10.1128/jvi.02148-09
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发表时间：
2010-01
影响因子：
5.4
通讯作者：
Jacqueline P. Upham;Danielle L. Pickett;T. Irimura;E. Margot Anders;P. Reading
中科院分区：
文献类型：
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作者：
Jacqueline P. Upham;Danielle L. Pickett;T. Irimura;E. Margot Anders;P. Reading
虽然唾液酸长期以来被认为是流感病毒附着于宿主细胞的主要受体决定簇，但对于任何细胞类型，介导病毒进入的特异性受体分子都是未知的。对于流感病毒对小鼠巨噬细胞的感染，我们早期的研究表明C型凝集素，巨噬细胞甘露糖受体（MMR）参与了这一过程。在这里，我们已经使用直接结合技术来确认和表征流感病毒与MMR的相互作用，并寻求可能具有作为病毒进入受体的潜力的其他巨噬细胞表面分子。我们确定了巨噬细胞半乳糖型凝集素（MGL）作为第二个巨噬细胞膜C型凝集素，结合流感病毒，是已知的内吞。流感病毒与MMR和MGL的结合通过两种凝集素的碳水化合物识别结构域对病毒聚糖的Ca 2+依赖性识别独立于唾液酸发生;流感病毒也与MMR上的唾液酸结合。MMR和MGL的多价配体以与这些受体在不同巨噬细胞群体上的表达相关的方式抑制流感病毒感染巨噬细胞。流感病毒株A/PR/8/34，其糖基化程度低，感染巨噬细胞的能力差，不能被MMR或MGL的C型凝集素活性识别。我们的结论是，凝集素介导的相互作用的流感病毒与MMR或MGL所需的内吞摄取的病毒进入巨噬细胞，这些凝集素，因此可以被认为是次要的或辅助受体与唾液酸感染这种细胞类型。
ABSTRACT Although sialic acid has long been recognized as the primary receptor determinant for attachment of influenza virus to host cells, the specific receptor molecules that mediate viral entry are not known for any cell type. For the infection of murine macrophages by influenza virus, our earlier study indicated involvement of a C-type lectin, the macrophage mannose receptor (MMR), in this process. Here, we have used direct binding techniques to confirm and characterize the interaction of influenza virus with the MMR and to seek additional macrophage surface molecules that may have potential as receptors for viral entry. We identified the macrophage galactose-type lectin (MGL) as a second macrophage membrane C-type lectin that binds influenza virus and is known to be endocytic. Binding of influenza virus to MMR and MGL occurred independently of sialic acid through Ca2+-dependent recognition of viral glycans by the carbohydrate recognition domains of the two lectins; influenza virus also bound to the sialic acid on the MMR. Multivalent ligands of the MMR and MGL inhibited influenza virus infection of macrophages in a manner that correlated with expression of these receptors on different macrophage populations. Influenza virus strain A/PR/8/34, which is poorly glycosylated and infects macrophages poorly, was not recognized by the C-type lectin activity of either the MMR or the MGL. We conclude that lectin-mediated interactions of influenza virus with the MMR or the MGL are required for the endocytic uptake of the virus into macrophages, and these lectins can thus be considered secondary or coreceptors with sialic acid for infection of this cell type.