Multi-virion infectious units arise from free viral particles in an enveloped virus
Multi-virion infectious units arise from free viral particles in an enveloped virus
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DOI：
10.1038/nmicrobiol.2017.78
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发表时间：
2017-07-01
影响因子：
28.3
通讯作者：
Sanjuan, Rafael
中科院分区：
文献类型：
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作者：
Cuevas, Jose M.;Duran-Moreno, Maria;Sanjuan, Rafael
许多动物病毒被包裹在从细胞膜上获取的脂质双层中。由于病毒表面蛋白结合到这些膜上启动感染，我们假设游离的病毒体也可能能够与细胞外的其他病毒体的包膜相互作用。在这里，我们证明了这一假设在水泡性口炎病毒（VSV），一个原型的负链RNA病毒组成的内部核糖核衣壳，基质蛋白和外部信封。利用显微镜，动态光散射，差速离心和流式细胞术，我们表明，游离的病毒颗粒可以自发聚集成多病毒粒子感染单位。我们还表明，在建立这些接触后，不同的病毒遗传变异体共同传播到同一靶细胞。此外，病毒体-病毒体结合可以决定病毒适应性的关键方面，例如抗体逃逸。在纯化的病毒体中，这一过程是由蛋白质-脂质相互作用驱动的，可能涉及VSV表面糖蛋白和磷脂酰丝氨酸。尽管我们发现多病毒体复合物在标准细胞培养物中不常见，但它们在其他液体如唾液中丰富，这是一种天然的VSV脱落途径。我们的研究结果与普遍接受的病毒粒子作为被动繁殖体的看法形成对比，并显示了包膜病毒建立集体感染单位的能力，这反过来又可以促进病毒-病毒相互作用和类社会特征的进化。
Many animal viruses are enveloped in a lipid bilayer taken up from cellular membranes. Because viral surface proteins bind to these membranes to initiate infection, we hypothesized that free virions may also be capable of interacting with the envelopes of other virions extracellularly. Here, we demonstrate this hypothesis in the vesicular stomatitis virus (VSV), a prototypic negative-strand RNAvirus composed of an internal ribonucleocapsid, a matrix protein and an external envelope. Using microscopy, dynamic light scattering, differential centrifugation and flow cytometry, we show that free viral particles can spontaneously aggregate into multi-virion infectious units. We also show that, following establishment of these contacts, different viral genetic variants are co-transmitted to the same target cell. Furthermore, virion-virion binding can determine key aspects of viral fitness such as antibody escape. In purified virions, this process is driven by protein-lipid interactions probably involving the VSV surface glycoprotein and phosphatidylserine. Whereas we found that multi-virion complexes occurred unfrequently in standard cell cultures, they were abundant in other fluids such as saliva, a natural VSV shedding route. Our findings contrast with the commonly accepted perception of virions as passive propagules and show the ability of enveloped viruses to establish collective infectious units, which could in turn facilitate the evolution of virus-virus interactions and of social-like traits.