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类生物膜样细胞外病毒组装体在病毒突触中介导 HTLV-1 细胞间传播。

Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses.

机构信息

Institut Pasteur, Unité de Biologie Cellulaire des Lymphocytes, Centre National de Recherche Scientifique (CNRS), Unité de Recherche Associée 1961, Paris, France.

出版信息

Nat Med. 2010 Jan;16(1):83-9. doi: 10.1038/nm.2065. Epub 2009 Dec 20.

Abstract

Human T cell leukemia virus type 1 (HTLV-1) is a lymphotropic retrovirus whose cell-to-cell transmission requires cell contacts. HTLV-1-infected T lymphocytes form 'virological synapses', but the mechanism of HTLV-1 transmission remains poorly understood. We show here that HTLV-1-infected T lymphocytes transiently store viral particles as carbohydrate-rich extracellular assemblies that are held together and attached to the cell surface by virally-induced extracellular matrix components, including collagen and agrin, and cellular linker proteins, such as tetherin and galectin-3. Extracellular viral assemblies rapidly adhere to other cells upon cell contact, allowing virus spread and infection of target cells. Their removal strongly reduces the ability of HTLV-1-producing cells to infect target cells. Our findings unveil a novel virus transmission mechanism based on the generation of extracellular viral particle assemblies whose structure, composition and function resemble those of bacterial biofilms. HTLV-1 biofilm-like structures represent a major route for virus transmission from cell to cell.

摘要

人类 T 细胞白血病病毒 1 型(HTLV-1)是一种嗜淋巴细胞逆转录病毒,其细胞间传播需要细胞接触。HTLV-1 感染的 T 淋巴细胞形成“病毒突触”,但 HTLV-1 传播的机制仍知之甚少。我们在这里表明,HTLV-1 感染的 T 淋巴细胞暂时储存富含碳水化合物的病毒颗粒作为细胞外聚集物,这些聚集物通过病毒诱导的细胞外基质成分(包括胶原和聚集素)和细胞连接蛋白(如 tetherin 和半乳糖凝集素-3)连接在一起并附着在细胞表面。细胞接触后,细胞外病毒聚集物迅速附着在其他细胞上,从而允许病毒传播和感染靶细胞。去除这些聚集物会强烈降低产生 HTLV-1 的细胞感染靶细胞的能力。我们的发现揭示了一种新的病毒传播机制,该机制基于细胞外病毒颗粒聚集物的产生,其结构、组成和功能类似于细菌生物膜。HTLV-1 生物膜样结构代表了病毒从一个细胞到另一个细胞传播的主要途径。

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