Sialoadhesin expressed on IFN-induced monocytes binds HIV-1 and enhances infectivity.
Sialoadhesin expressed on IFN-induced monocytes binds HIV-1 and enhances infectivity.
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DOI：
10.1371/journal.pone.0001967
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发表时间：
2008-04-16
期刊：
影响因子：
3.7
通讯作者：
Pulliam L
中科院分区：
文献类型：
--
作者：
Rempel H;Calosing C;Sun B;Pulliam L
HIV-1感染使免疫系统失调并改变循环单核细胞的基因表达。对感染HIV-1的受试者的CD14+单核细胞的差异基因表达分析显示，唾液粘附素（Sn, CD169, Siglec 1）的表达增加，这是一种细胞粘附分子，首次在慢性炎症性疾病中激活的巨噬细胞亚群中被描述。我们通过流式细胞术分析了唾液黏附素在CD14+单核细胞上的表达，发现病毒载量升高的受试者的表达明显高于病毒载量未检测到的受试者。在健康个体培养的CD14+单核细胞中，干扰素-α和干扰素-γ诱导唾液粘附素表达，但不诱导肿瘤坏死因子-α表达。通过严格的结合实验，表达唾液粘附素的单核细胞通过与病毒包膜糖蛋白gp120上的唾液酸残基相互作用来吸附HIV-1。此外，表达唾液黏附素的单核细胞促进了在没有单核细胞自身感染的情况下允许细胞的HIV-1转移感染。在HIV-1感染后，CD14+单核细胞上唾液粘附素表达增加，其最大表达与高病毒载量相关。我们发现干扰素在原代CD14+单核细胞中诱导唾液粘附素，这与病毒血症期间的抗病毒反应是一致的。我们的研究结果表明，循环唾液粘附素表达的单核细胞能够结合HIV-1并有效地将病毒传递到靶细胞，从而增强HIV-1的分布。唾液粘附素可以在单核细胞免疫监视或迁移到炎症部位时将HIV-1传播到病毒库，然后促进HIV-1感染许可细胞。
HIV-1 infection dysregulates the immune system and alters gene expression in circulating monocytes. Differential gene expression analysis of CD14+ monocytes from subjects infected with HIV-1 revealed increased expression of sialoadhesin (Sn, CD169, Siglec 1), a cell adhesion molecule first described in a subset of macrophages activated in chronic inflammatory diseases. We analyzed sialoadhesin expression on CD14+ monocytes by flow cytometry and found significantly higher expression in subjects with elevated viral loads compared to subjects with undetectable viral loads. In cultured CD14+ monocytes isolated from healthy individuals, sialoadhesin expression was induced by interferon-α and interferon-γ but not tumor necrosis factor-α. Using a stringent binding assay, sialoadhesin-expressing monocytes adsorbed HIV-1 through interaction with the sialic acid residues on the viral envelope glycoprotein gp120. Furthermore, monocytes expressing sialoadhesin facilitated HIV-1 trans infection of permissive cells, which occurred in the absence of monocyte self-infection. Increased sialoadhesin expression on CD14+ monocytes occurred in response to HIV-1 infection with maximum expression associated with high viral load. We show that interferons induce sialoadhesin in primary CD14+ monocytes, which is consistent with an antiviral response during viremia. Our findings suggest that circulating sialoadhesin-expressing monocytes are capable of binding HIV-1 and effectively delivering virus to target cells thereby enhancing the distribution of HIV-1. Sialoadhesin could disseminate HIV-1 to viral reservoirs during monocyte immunosurveillance or migration to sites of inflammation and then facilitate HIV-1 infection of permissive cells.
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