DC-SIGN Mediates Cell-Free Infection and Transmission of Human T-Cell Lymphotropic Virus Type 1 by Dendritic Cells
DC-SIGN Mediates Cell-Free Infection and Transmission of Human T-Cell Lymphotropic Virus Type 1 by Dendritic Cells
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DOI：
10.1128/jvi.01054-09
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发表时间：
2009-11-01
影响因子：
5.4
通讯作者：
Wigdahl, Brian
中科院分区：
文献类型：
--
作者：
Jain, Pooja;Manuel, Sharron L.;Wigdahl, Brian
尽管树突状细胞（DCs）对人类T细胞嗜淋巴细胞病毒1型（HTLV-1）感染的易感性以及这些细胞在疾病发病机制中的明确作用，但病毒与DCs结合的机制尚未完全阐明。最近，葡萄糖转运蛋白，GLUT-1，硫酸乙酰肝素蛋白聚糖（HSPGs），和神经纤毛蛋白-1（NRP-1）被证明有助于HTLV-1进入T细胞。DC表达其自身的一系列抗原受体，最重要的是与逆转录病毒结合的DC特异性细胞间粘附分子-3（ICAM-3）-抓取非整合素（DC-SIGN）。因此，DC-SIGN和其他HTLV-1附着因子在病毒结合、传播和生产性感染中的作用使用单核细胞来源的DC（MDDC）、血髓样DC和表达DC-SIGN的B细胞系进行分析。首先在DC和B细胞系上检查DC-SIGN、GLUT-1、HSPGs和NRP-1的相对表达。尽管这些分子的抑制降低了病毒结合，但HTLV-1从DC向T细胞的传递主要由DC-SIGN介导。DC-SIGN还显示在MDDC以及模型B细胞系的感染中起作用。在病毒诱导的白细胞介素-4产生和随后的DC-SIGN表达增强后，MDDC的HTLV-1感染也在血液髓样DC中实现。这项研究代表了DC上潜在的HTLV-1受体的第一次全面分析，并强烈表明DC-SIGN在HTLV-1结合，传播和感染中起着关键作用，从而为抗逆转录病毒治疗和杀微生物剂的开发提供了有吸引力的靶点。
Despite the susceptibility of dendritic cells (DCs) to human T-cell lymphotropic virus type 1 (HTLV-1) infection and the defined role of these cells in disease pathogenesis, the mechanisms of viral binding to DCs have not been fully delineated. Recently, a glucose transporter, GLUT-1, heparan sulfate proteoglycans (HSPGs), and neuropilin-1 (NRP-1) were demonstrated to facilitate HTLV-1 entry into T cells. DCs express their own array of antigen receptors, the most important being the DC-specific intercellular adhesion molecule-3 (ICAM-3)-grabbing nonintegrin (DC-SIGN) with respect to retrovirus binding. Consequently, the role of DC-SIGN and other HTLV-1 attachment factors was analyzed in viral binding, transmission, and productive infection using monocyte-derived DCs (MDDCs), blood myeloid DCs, and B-cell lines expressing DC-SIGN. The relative expression of DC-SIGN, GLUT-1, HSPGs, and NRP-1 first was examined on both DCs and B-cell lines. Although the inhibition of these molecules reduced viral binding, HTLV-1 transmission from DCs to T cells was mediated primarily by DC-SIGN. DC-SIGN also was shown to play a role in the infection of MDDCs as well as model B-cell lines. The HTLV-1 infection of MDDCs also was achieved in blood myeloid DCs following the enhancement of virus-induced interleukin-4 production and subsequent DC-SIGN expression in this cell population. This study represents the first comprehensive analysis of potential HTLV-1 receptors on DCs and strongly suggests that DC-SIGN plays a critical role in HTLV-1 binding, transmission, and infection, thereby providing an attractive target for the development of antiretroviral therapeutics and microbicides.