HSV-1 Glycoproteins Are Delivered to Virus Assembly Sites Through Dynamin-Dependent Endocytosis.
HSV-1 Glycoproteins Are Delivered to Virus Assembly Sites Through Dynamin-Dependent Endocytosis.
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DOI：
10.1111/tra.12340
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发表时间：
2016-01
期刊：
影响因子：
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通讯作者：
Crump CM
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文献类型：
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作者：
Albecka A;Laine RF;Janssen AF;Kaminski CF;Crump CM
单纯疱疹病毒-1（HSV-1）是一种大包膜DNA病毒，属于疱疹病毒科。最近已经表明，包裹新组装的衣壳的细胞质膜是来自质膜的内吞隔室。在这里，我们表明动力蛋白依赖性内吞作用在这一过程中起着重要作用。显性负性发动蛋白和网格蛋白衔接子AP 180显著降低病毒产生。此外，靶向发动蛋白和网格蛋白的抑制剂导致糖蛋白向细胞质衣壳的转运减少，证实糖蛋白通过内吞作用递送至组装位点。我们还表明，某些组合的糖蛋白相互共定位，并与网格蛋白依赖性和非依赖性的内吞途径的组件。重要的是，我们证明了当中和抗体在病毒颗粒组装过程中暴露在细胞表面时，中和抗体与糖蛋白结合，导致产生非感染性HSV-1。我们的研究结果表明，运输病毒糖蛋白的质膜之前的内吞作用是这些蛋白质定位到细胞质病毒装配室的主要途径。这突出了内吞作用作为HSV-1表达过程中主要蛋白分选事件的重要性。
Herpes simplex virus‐1 (HSV‐1) is a large enveloped DNA virus that belongs to the family of Herpesviridae. It has been recently shown that the cytoplasmic membranes that wrap the newly assembled capsids are endocytic compartments derived from the plasma membrane. Here, we show that dynamin‐dependent endocytosis plays a major role in this process. Dominant‐negative dynamin and clathrin adaptor AP180 significantly decrease virus production. Moreover, inhibitors targeting dynamin and clathrin lead to a decreased transport of glycoproteins to cytoplasmic capsids, confirming that glycoproteins are delivered to assembly sites via endocytosis. We also show that certain combinations of glycoproteins colocalize with each other and with the components of clathrin‐dependent and ‐independent endocytosis pathways. Importantly, we demonstrate that the uptake of neutralizing antibodies that bind to glycoproteins when they become exposed on the cell surface during virus particle assembly leads to the production of non‐infectious HSV‐1. Our results demonstrate that transport of viral glycoproteins to the plasma membrane prior to endocytosis is the major route by which these proteins are localized to the cytoplasmic virus assembly compartments. This highlights the importance of endocytosis as a major protein‐sorting event during HSV‐1 envelopment.