DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets
DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets
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DOI：
10.1128/jvi.00136-06
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发表时间：
2006-09-01
影响因子：
5.4
通讯作者：
Poehlmann, Stefan
中科院分区：
文献类型：
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作者：
Chaipan, Chawaree;Soilleux, Elizabeth J.;Poehlmann, Stefan
血小板可以吞噬人类免疫缺陷病毒1型（HIV-1），感染者血液中大量的HIV-1与这些细胞有关。然而，目前还不清楚血小板如何捕获HIV-1以及血小板相关病毒是否具有传染性。DC-SIGN和其他凝集素有助于树突状细胞（DC）捕获HIV-1，并促进HIV-1在DC/T细胞共培养物中的传播。在这里，我们表明，血小板表达C型凝集素样受体2（CLEC-2）和低水平的DC-SIGN。CLEC-2与HIV-1结合，而不管病毒包膜蛋白的存在，并促进血小板对HIV-1的捕获。然而，血小板的HIV-1结合活性的很大一部分依赖于DC-SIGN。DC-SIGN和CLEC-2抑制剂的组合强烈降低了HIV-1与血小板的结合，表明这些凝集素是HIV-1与血小板有效结合所必需的。捕获的HIV-1在几天内保持感染状态，这表明HIV-1可以逃避血小板的降解，并可能利用这些细胞促进其传播。我们的研究结果确定CLEC-2作为一种新的HIV-1附着因子，并提供证据表明血小板通过DC-SIGN和CLEC-2捕获和转移感染性HIV-1，从而可能促进HIV-1在感染患者中的传播。
Platelets can engulf human immunodeficiency virus type 1 (HIV-1), and a significant amount of HIV-1 in the blood of infected individuals is associated with these cells. However, it is unclear how platelets capture HIV-1 and whether platelet-associated virus remains infectious. DC-SIGN and other lectins contribute to capture of HIV-1 by dendritic cells (DCs) and facilitate HIV-1 spread in DC/T-cell cocultures. Here, we show that platelets express both the C-type lectin-like receptor 2 (CLEC-2) and low levels of DC-SIGN. CLEC-2 bound to HIV-1, irrespective of the presence of the viral envelope protein, and facilitated HIV-1 capture by platelets. However, a substantial fraction of the HIV-1 binding activity of platelets was dependent on DC-SIGN. A combination of DC-SIGN and CLEC-2 inhibitors strongly reduced HIV-1 association with platelets, indicating that these lectins are required for efficient HIV-1 binding to platelets. Captured HIV-1 was maintained in an infectious state over several days, suggesting that HIV-1 can escape degradation by platelets and might use these cells to promote its spread. Our results identify CLEC-2 as a novel HIV-1 attachment factor and provide evidence that platelets capture and transfer infectious HIV-1 via DC-SIGN and CLEC-2, thereby possibly facilitating HIV-1 dissemination in infected patients.