Galectin-1 promotes HIV-1 infectivity in macrophages through stabilization of viral adsorption

Galectin-1 promotes HIV-1 infectivity in macrophages through stabilization of viral adsorption
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DOI:
10.1016/j.virol.2007.09.034
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发表时间:
2008-02-05
期刊:
影响因子:
3.7
通讯作者:
Sato, Sachiko
Sato, Sachiko
中科院分区:
医学3区
文献类型:
--
作者:
Mercier, Simon;St-Pierre, Christian;Sato, Sachiko

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在原发感染人类免疫缺陷病毒1型(HIV-1)后,巨噬细胞被认为起着重要作用,因为它们是病毒遇到的第一个靶细胞之一,也可以在很长一段时间内维持大量的病毒生产。虽然原代细胞受体CD4和病毒编码的外包膜糖蛋白gp120之间的相互作用启动了感染过程,但已有研究表明,HIV-1利用各种宿主因子促进在细胞表面的吸附。在感染部位发现的巨噬细胞和其他细胞可以分泌一种可溶性哺乳动物凝集素,半乳糖凝集素-1,它通过其碳水化合物识别区域与-半乳糖苷残基结合。半乳糖凝集素-1是一种二聚体,可以交联不同成分上表达的配体,介导细胞间或细胞与病原体之间的粘附。我们在这里报告了半乳糖凝集素-1,而不是半乳糖凝集素-3,增加了单核细胞来源的巨噬细胞(MDMs)的HIV-1传染性。这种现象可能是由于病毒吸附动力学的增强,从而促进了HIV-1的进入。融合抑制剂T-20和TAK779即使在半乳糖凝集素-1存在的情况下仍能有效减少感染,这表明半乳糖凝集素-1介导的作用发生在融合前的一个步骤。总之,我们的数据表明,半乳糖凝集素-1可以通过促进病毒复制周期的早期事件(即吸附)促进MDMs中的HIV-1感染。(c) 2007爱思唯尔公司版权所有。
Following primary infection with human immunodeficiency virus type-1 (HIV-1), macrophages are thought to play an important role, as they are one of the first target cells the virus encounters and can also sustain a significant production of viruses over extended periods of time. While the interaction between the primary cellular receptor CD4 and the virus-encoded external envelope glycoprotein gp120 initiates the infection process, it has been suggested that various host factors are exploited by HIV-1 to facilitate adsorption onto the cell surface. Macrophages and other cells found at the infection site can secrete a soluble mammalian lectin, galectin-1, which binds to beta-galactoside residues through its carbohydrate recognition domain. Being a dimer, galectin-1 can cross-link ligands expressed on different constituents to mediate adhesion between cells or between cells and pathogens. We report here that galectin-1, but not galectin-3, increased HIV-1 infectivity in monocyte-derived macrophages (MDMs). This phenomenon was likely due to an enhancement of virus adsorption kinetics, which facilitates HIV-1 entry. The fusion inhibitors T-20 and TAK779 remained effective at reducing infection even in the presence of galectin-1, indicating that the galectin-1-mediated effect is occurring at a step prior to fusion. Together, our data suggest that galectin-1 can facilitate HIV-1 infection in MDMs by promoting early events of the virus replicative cycle (i.e. adsorption). (c) 2007 Elsevier Inc. All rights reserved.