为什么包膜病毒需要核心--核衣壳核心对病毒出芽的贡献
Why enveloped viruses need cores -- the contribution of a nucleocapsid core to viral budding
摘要:
在甲病毒的生命周期中,核衣壳核心通过细胞膜出芽以获得脂质膜和病毒糖蛋白的外包膜。然而,核衣壳核心的存在对于感染性颗粒的组装不是必需的。为了确定核衣壳核心的作用,我们开发了一个粗粒度的计算模型,我们调查作为糖蛋白和核衣壳相互作用的函数的出芽动力学,以及在没有核衣壳的情况下出芽。我们发现,有一个糖蛋白定向出芽和核衣壳定向出芽之间的过渡发生在核衣壳相互作用的阈值强度以上。模拟预测,糖蛋白定向出芽导致显着增加的大小多分散性和颗粒多态性。这种多分散性可以定性地解释占膜和糖蛋白壳的弯曲能之间的竞争的理论模型。模拟还表明,一个萌芽颗粒的几何形状导致亚基扩散的障碍,这可能会导致停滞,部分萌芽状态。我们提出了一个相图,这个和其他形态的出芽粒子。这些结构与实验的比较,可以建立边界是否出芽是由糖蛋白或核衣壳相互作用。虽然我们的模型是出于甲病毒,我们讨论了我们的结果对其他包膜病毒的影响。
英文摘要:
During the alphavirus lifecycle, a nucleocapsid core buds through the cell membrane to acquire an outer envelope of lipid membrane and viral glycoproteins. However, the presence of a nucleocapsid core is not required for assembly of infectious particles. To determine the role of the nucleocapsid core, we develop a coarse-grained computational model with which we investigate budding dynamics as a function of glycoprotein and nucleocapsid interactions, as well as budding in the absence of a nucleocapsid. We find that there is a transition between glycoprotein-directed budding and nucleocapsid-directed budding which occurs above a threshold strength of nucleocapsid interactions. The simulations predict that glycoprotein-directed budding leads to significantly increased size polydispersity and particle polymorphism. This polydispersity can be qualitatively explained by a theoretical model accounting for the competition between bending energy of the membrane and the glycoprotein shell. The simulations also show that the geometry of a budding particle leads to a barrier to subunit diffusion, which can result in a stalled, partially budded state. We present a phase diagram for this and other morphologies of budded particles. Comparison of these structures against experiments could establish bounds on whether budding is directed by glycoprotein or nucleocapsid interactions. Although our model is motivated by alphaviruses, we discuss implications of our results for other enveloped viruses.
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