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碳水化合物结合剂的抗病毒活性及DC-SIGN在登革病毒感染中的作用

Antiviral activity of carbohydrate-binding agents and the role of DC-SIGN in dengue virus infection.

作者信息

Alen Marijke M F, Kaptein Suzanne J F, De Burghgraeve Tine, Balzarini Jan, Neyts Johan, Schols Dominique

机构信息

Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.

出版信息

Virology. 2009 Apr 25;387(1):67-75. doi: 10.1016/j.virol.2009.01.043. Epub 2009 Mar 4.

DOI:10.1016/j.virol.2009.01.043
PMID:19264337
Abstract

Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) is an important binding receptor for dengue virus (DENV) that recognizes N-glycosylation sites on the viral E-glycoprotein. DENV cannot bind nor infect the human B-cell line Raji/0. However, DENV productively infects Raji/DC-SIGN(+) cells that constitutively express DC-SIGN on their surface. IL-4-treated monocytes, expressing high levels of DC-SIGN, are also susceptible for DENV infection. Several carbohydrate-binding agents (CBAs), such as the plant lectins HHA, GNA (mannose-specific) and UDA (N-acetylglucosamine-specific), inhibited dose-dependently the binding of DENV and subsequently viral replication in Raji/DC-SIGN(+) cells (EC(50): 0.1-2.2 microM). These CBAs were clearly more active against DENV in IL-4-treated monocytes (EC(50): 4-56 nM). However, the CBAs were devoid of antiviral activity in DENV-susceptible Vero-B (DC-SIGN(-)) cells, demonstrating cell type-dependent differences in viral entry mechanisms.

摘要

树突状细胞特异性细胞间黏附分子3结合非整合素(DC-SIGN)是登革病毒(DENV)的一种重要结合受体,可识别病毒E糖蛋白上的N-糖基化位点。DENV无法结合也不能感染人B细胞系Raji/0。然而,DENV能有效感染在其表面组成性表达DC-SIGN的Raji/DC-SIGN(+)细胞。经白细胞介素-4处理的单核细胞,高水平表达DC-SIGN,也易受DENV感染。几种碳水化合物结合剂(CBA),如植物凝集素HHA、GNA(甘露糖特异性)和UDA(N-乙酰葡糖胺特异性),在Raji/DC-SIGN(+)细胞中剂量依赖性地抑制DENV的结合及随后的病毒复制(半数有效浓度:0.1 - 2.2微摩尔)。这些CBA在经白细胞介素-4处理的单核细胞中对DENV的活性明显更高(半数有效浓度:4 - 56纳摩尔)。然而,CBA在对DENV敏感的Vero-B(DC-SIGN(-))细胞中没有抗病毒活性,这表明病毒进入机制存在细胞类型依赖性差异。

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