Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry
Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry
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DOI：
10.1128/jvi.78.6.2943-2947.2004
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发表时间：
2004-03-01
影响因子：
5.4
通讯作者：
Kawaoka, Y
中科院分区：
文献类型：
--
作者：
Takada, A;Fujioka, K;Kawaoka, Y
丝状病毒在人类和非人类灵长类动物中引起致命的出血性疾病。丝状病毒感染的最初目标是单核吞噬细胞。钙依赖性（c型）凝集素，如树突状细胞或肝/淋巴结特异性ICAM-3非整合素（分别为DC-SIGN或L-SIGN），以及肝asialal糖蛋白受体，与埃博拉病毒或马尔堡病毒糖蛋白（GP）结合，并在体外增强这些病毒的传染性。在这里，我们证明了最近发现的一种人巨噬细胞半乳糖和n -乙酰半乳糖胺特异性c型凝集素（hMGL），其配体特异性不同于DC-SIGN和L-SIGN，也能增强丝状病毒的传染性。莱斯顿病毒和马尔堡病毒的这种增强作用明显弱于高致病性扎伊尔病毒。我们还表明，丝状病毒GP上高度糖基化的粘蛋白样结构域是与这种凝集素有效相互作用所必需的。此外，hMGL，像DC-SIGN和L-SIGN一样，存在于已知的线状病毒主要靶点细胞（即巨噬细胞和树突状细胞）上，这表明这些c型凝集素在体内病毒复制中起作用。我们提出丝状病毒根据细胞类型使用不同的c型凝集素进入细胞，并促进有效的病毒复制。
Filoviruses cause lethal hemorrhagic disease in humans and nonhuman primates. An initial target of filovirus infection is the mononuclear phagocytic cell. Calcium-dependent (C-type) lectins such as dendritic cell- or liver/lymph node-specific ICAM-3 grabbing nonintegrin (DC-SIGN or L-SIGN, respectively), as well as the hepatic asialoglycoprotein receptor, bind to Ebola or Marburg virus glycoprotein (GP) and enhance the infectivity of these viruses in vitro. Here, we demonstrate that a recently identified human macrophage galactose- and N-acetylgalactosamine- specific C-type lectin (hMGL), whose ligand specificity differs from DC-SIGN and L-SIGN, also enhances the infectivity of filoviruses. This enhancement was substantially weaker for the Reston and Marburg viruses than for the highly pathogenic Zaire virus. We also show that the heavily glycosylated, mucin-like domain on the filovirus GP is required for efficient interaction with this lectin. Furthermore, hMGL, like DC-SIGN and L-SIGN, is present on cells known to be major targets of filoviruses (i.e., macrophages and dendritic cells), suggesting a role for these C-type lectins in viral replication in vivo. We propose that filoviruses use different C-type lectins to gain cellular entry, depending on the cell type, and promote efficient viral replication.