Tetraspanins are master organizers of the cell membrane. Recent evidence suggests that tetraspanins themselves may become crowded by virus particles and that these crowds/aggregates co-internalize with the viral particles. Using microscopy, we studied human papillomavirus (HPV) type 16-dependent aggregates on the cell surface of tetraspanin overexpressing keratinocytes. We find that aggregates are (1) rich in at least two different tetraspanins, (2) three-dimensional architectures extending up to several micrometers into the cell, and (3) decorated intracellularly by filamentous actin. Moreover, in cells not overexpressing tetraspanins, we note that obscurin-like protein 1 (OBSL1), which is thought to be a cytoskeletal adaptor, associates with filamentous actin. We speculate that HPV contact with the cell membrane could trigger the formation of a large tetraspanin web. This web may couple the virus contact site to the intracellular endocytic actin machinery, possibly involving the cytoskeletal adaptor protein OBSL1. Functionally, such a tetraspanin web could serve as a virus entry platform, which is co-internalized with the virus particle.

中文翻译：

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HPV 被四跨膜蛋白网捕获？

四跨膜蛋白是细胞膜的主要组织者。最近的证据表明，四跨膜蛋白本身可能会被病毒颗粒拥挤，并且这些人群/聚集体与病毒颗粒共同内化。使用显微镜，我们研究了四跨膜蛋白过表达角质形成细胞的细胞表面上的人乳头瘤病毒 (HPV) 16 型依赖性聚集体。我们发现聚集体（1）富含至少两种不同的四跨膜蛋白，（2）延伸至细胞内数微米的三维结构，以及（3）在细胞内由丝状肌动蛋白装饰。此外，在未过度表达四跨膜蛋白的细胞中，我们注意到暗蛋白样蛋白 1 (OBSL1)（被认为是一种细胞骨架接头）与丝状肌动蛋白相关。我们推测 HPV 与细胞膜的接触可能引发大的四跨膜蛋白网的形成。该网络可能将病毒接触位点与细胞内胞吞肌动蛋白机制偶联，可能涉及细胞骨架衔接蛋白 OBSL1。从功能上讲，这种四跨膜蛋白网可以作为病毒进入平台，与病毒颗粒共同内化。