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麻疹病毒从树突状细胞向 T 细胞的传播:集中病毒和细胞成分的突触样界面的形成。

Measles virus transmission from dendritic cells to T cells: formation of synapse-like interfaces concentrating viral and cellular components.

机构信息

Institute for Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.

出版信息

J Virol. 2012 Sep;86(18):9773-81. doi: 10.1128/JVI.00458-12. Epub 2012 Jul 3.

Abstract

Transmission of measles virus (MV) to T cells by its early CD150(+) target cells is considered to be crucial for viral dissemination within the hematopoietic compartment. Using cocultures involving monocyte-derived dendritic cells (DCs) and T cells, we now show that T cells acquire MV most efficiently from cis-infected DCs rather than DCs having trapped MV (trans-infection). Transmission involves interactions of the viral glycoprotein H with its receptor CD150 and is therefore more efficient to preactivated T cells. In addition to rare association with actin-rich filopodial structures, the formation of contact interfaces consistent with that of virological synapses (VS) was observed where viral proteins accumulated and CD150 was redistributed in an actin-dependent manner. In addition to these molecules, activated LFA-1, DC-SIGN, CD81, and phosphorylated ezrin-radixin-moesin proteins, which also mark the HIV VS, redistributed toward the MV VS. Most interestingly, moesin and substance P receptor, both implicated earlier in assisting MV entry or cell-to-cell transmission, also partitioned to the transmission structure. Altogether, the MV VS shares important similarities to the HIV VS in concentrating cellular components potentially regulating actin dynamics, conjugate stability, and membrane fusion as required for efficient entry of MV into target T cells.

摘要

麻疹病毒 (MV) 通过其早期的 CD150(+)靶细胞向 T 细胞的传播被认为是病毒在造血细胞内传播的关键。通过涉及单核细胞衍生的树突状细胞 (DC) 和 T 细胞的共培养,我们现在表明,T 细胞从顺式感染的 DC 中最有效地获得 MV,而不是从捕获 MV(转染)的 DC 中获得。这种传递涉及病毒糖蛋白 H 与其受体 CD150 的相互作用,因此对预激活的 T 细胞更有效。除了与富含肌动蛋白的丝状伪足结构的罕见关联外,还观察到与病毒学突触 (VS) 一致的接触界面的形成,其中病毒蛋白积累并且 CD150 以肌动蛋白依赖性方式重新分布。除了这些分子之外,激活的 LFA-1、DC-SIGN、CD81 和磷酸化的 ezrin-radixin-moesin 蛋白也重新分布到 MV VS,这些蛋白也标记了 HIV VS。最有趣的是,早期参与协助 MV 进入或细胞间传播的 moesin 和 P 物质受体也分配到了传递结构中。总之,MV VS 与 HIV VS 有许多重要的相似之处,它集中了潜在调节肌动蛋白动力学、共轭稳定性和膜融合的细胞成分,这是 MV 有效进入靶 T 细胞所必需的。

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