Galectin-1 acts as a soluble host factor that promotes HIV-1 infectivity through stabilization of virus attachment to host cells
Galectin-1 acts as a soluble host factor that promotes HIV-1 infectivity through stabilization of virus attachment to host cells
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DOI：
10.4049/jimmunol.174.7.4120
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Tremblay, MJ
中科院分区：
文献类型：
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作者：
Ouellet, M;Mercier, S;Tremblay, MJ
人类免疫缺陷病毒1型(HIV-1)感染的建立是通过病毒粒子稳定附着在靶细胞表面而开始的。尽管这一过程主要依赖于病毒编码的gp120和细胞表面CD4之间的相互作用，但许多不同的相互作用影响HIV-1与宿主细胞的结合。在这项研究中，我们报告了Galectin-1，一种二聚体β-半乳糖苷结合蛋白，促进R5，X4和R5X4变体的感染。Galectin-1作为一种可溶性的黏附分子，促进HIV-1与细胞表面的黏附。这一假设建立在实验的基础上，其中Galectin-1使HIV-1颗粒对阻止HIV-1吸附和共受体结合的各种试剂(即阻断抗CD4、可溶性CD4、人抗HIV-1多克隆抗体、基质细胞衍生因子-1a；RANTES)更具抵抗力。用融合抑制剂T-20进行的实验证实，Galectin-1主要影响HIV-1的附着。目前的发现与HIV-1感染的发病机制相关，这是因为Galectin-1在胸腺和淋巴结中大量表达，这两个器官代表了HIV-1的主要储存库。此外，Galectin-1由激活的CD8(+)T淋巴细胞分泌，在HIV-1阳性患者中发现大量CD8(+)T淋巴细胞。因此，在HIV-1复制位点以外分泌方式释放的Galectin-1可以使HIV-1与靶细胞交联，并促进病毒与细胞表面更牢固的黏附，从而提高感染过程的效率。总体而言，我们的发现表明Galectin-1可能影响HIV-1感染的发病机制。
The establishment of HIV type 1 (HIV-1) infection is initiated by the stable attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between virus-encoded gp120 and cell surface CD4, a number of distinct interactions influence binding of HIV-1 to host cells. In this study, we report that galectin-1, a dimeric beta-galactoside-binding protein, promotes infection with R5, X4, and R5X4 variants. Galectin-1 acts as a soluble adhesion molecule by facilitating attachment of HIV-1 to the cell surface. This postulate is based on experiments where galectin-1 rendered HIV-1 particles more refractory to various agents that block HIV-1 adsorption and coreceptor binding (i.e., a blocking anti-CD4, soluble CD4, human anti-HIV-1 polyclonal Abs; stromal cell-derived factor-la; RANTES). Experiments performed with the fusion inhibitor T-20 confirmed that galectin-1 is primarily affecting HIV-1 attachment. The relevance of the present findings for the pathogenesis of HIV-1 infection is provided by the fact that galectin-1 is abundantly expressed in the thymus and lymph nodes, organs that represent major reservoirs for HIV-1. Moreover, galectin-1 is secreted by activated CD8(+) T lymphocytes, which are found in high numbers in HIV-1-positive patients. Therefore, it is proposed that galectin-1, which is released in an exocrine fashion at HIV-1 replication sites, can cross-link HIV-1 and target cells and promote a firmer adhesion of the virus to the cell surface, thereby augmenting the efficiency of the infection process. Overall, our findings suggest that galectin-1 might affect the pathogenesis of HIV-1 infection.