Institut Pasteur, Unité de Biologie Cellulaire des Lymphocytes, Centre National de Recherche Scientifique (CNRS), Unité de Recherche Associée 1961, Paris, France.
Nat Med. 2010 Jan;16(1):83-9. doi: 10.1038/nm.2065. Epub 2009 Dec 20.
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.
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。