Role of Ebola Virus Secreted Glycoproteins and Virus-Like Particles in Activation of Human Macrophages
Role of Ebola Virus Secreted Glycoproteins and Virus-Like Particles in Activation of Human Macrophages
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埃博拉病毒分泌的糖蛋白和病毒样颗粒在人类巨噬细胞激活中的作用
DOI：
10.1128/jvi.79.4.2413-2419.2005
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发表时间：
2005
影响因子：
5.4
通讯作者：
Feldmann
中科院分区：
文献类型：
--
作者：
Wahl-Jensen;Hazelton;Schnittler;Stroher;Burton;Feldmann
埃博拉病毒是丝状病毒科的一种，引起最严重的病毒性出血热之一。在疾病的终末期，症状进展为低血压、凝血障碍和血栓，并且单核吞噬细胞和网状内皮系统显著受累。单核吞噬细胞系统的细胞是主要的靶细胞和炎症介质的产生者。埃博拉病毒在感染期间有效地产生四种可溶性糖蛋白：sGP、δ肽（Δ-肽）、GP 1和GP 1，2Δ。虽然这些糖蛋白的存在已在血液（sGP）和体外系统中得到证实，但假设它们在发病机制中具有生物学相关性，特别是靶细胞活化。为了深入了解它们的功能，我们在哺乳动物细胞中表达了四种可溶性糖蛋白，并对其进行了纯化和表征。还研究了跨膜糖蛋白在病毒样颗粒中的作用。用糖蛋白和病毒样颗粒处理原代人巨噬细胞，随后通过检测几种关键的促炎细胞因子（肿瘤坏死因子α、白细胞介素-6 [IL-6]和IL-1 β）和趋化因子IL-8来检测活化。糖蛋白的呈递被确定为是关键的，因为病毒样颗粒而不是可溶性糖蛋白诱导高水平的活化。我们认为GP 1，2以刚性形式呈现，如在颗粒表面上观察到的，对于启动足够的信号以激活原代靶细胞是至关重要的。在埃博拉病毒感染期间，分泌的糖蛋白似乎在这些细胞的外源性激活中不起任何作用。
Ebola virus, a member of the familyFiloviridae, causes one of the most severe forms of viral hemorrhagic fever. In the terminal stages of disease, symptoms progress to hypotension, coagulation disorders, and hemorrhages, and there is prominent involvement of the mononuclear phagocytic and reticuloendothelial systems. Cells of the mononuclear phagocytic system are primary target cells and producers of inflammatory mediators. Ebola virus efficiently produces four soluble glycoproteins during infection: sGP, delta peptide (Δ-peptide), GP1, and GP1,2Δ. While the presence of these glycoproteins has been confirmed in blood (sGP) and in vitro systems, it is hypothesized that they are of biological relevance in pathogenesis, particularly target cell activation. To gain insight into their function, we expressed the four soluble glycoproteins in mammalian cells and purified and characterized them. The role of the transmembrane glycoprotein in the context of virus-like particles was also investigated. Primary human macrophages were treated with glycoproteins and virus-like particles and subsequently tested for activation by detection of several critical proinflammatory cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], and IL-1 beta) and the chemokine IL-8. The presentation of the glycoprotein was determined to be critical since virus-like particles, but not soluble glycoproteins, induced high levels of activation. We propose that the presentation of GP1,2in the rigid form such as that observed on the surface of particles is critical for initiating a sufficient signal for the activation of primary target cells. The secreted glycoproteins do not appear to play any role in exogenous activation of these cells during Ebola virus infection.
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DOI：
10.1073/pnas.95.11.6032
发表时间：
1998-05-26
影响因子：
11.1
作者：
Weissenhorn, W;Calder, LJ;Wiley, DC
通讯作者：
Wiley, DC
DOI：
10.1073/pnas.2237038100
发表时间：
2003-12-23
影响因子：
11.1
作者：
Warfield, KL;Bosio, CM;Bavari, S
通讯作者：
Bavari, S
影响因子：
16
作者：
Weissenhorn, W;Carfi, A;Wiley, DC
通讯作者：
Wiley, DC
与致命的埃博拉病毒感染相关的干扰素 (IFN)-γ、IFN-α、白细胞介素 (IL)-2、IL-10 和肿瘤坏死因子-α 水平显着升高。
影响因子：
6.4
作者：
F. Villinger;P. Rollin;S. Brar;N. Chikkala;J. Winter;J. Sundstrom;S. Zaki;R. Swanepoel;A. Ansari;C. Peters
通讯作者：
C. Peters
影响因子：
4.4
作者：
Hensley, LE;Young, HA;Geisbert, TW
通讯作者：
Geisbert, TW