Martin Fisher School of Physics, Brandeis University, Waltham, Massachusetts.
Department of Biology, Indiana University, Bloomington, Indiana.
Biophys J. 2018 Feb 6;114(3):619-630. doi: 10.1016/j.bpj.2017.11.3782.
During the lifecycle of many enveloped viruses, 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 that 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 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.
在许多包膜病毒的生命周期中，核衣壳核心通过细胞膜出芽，获得脂质膜和病毒糖蛋白的外层包膜。然而，组装感染性颗粒并不需要核衣壳核心的存在。为了确定核衣壳核心的作用，我们开发了一个粗粒化计算模型，通过该模型研究了糖蛋白和核衣壳相互作用以及在没有核衣壳的情况下出芽的出芽动力学。我们发现，在核衣壳相互作用的强度超过阈值时，会发生糖蛋白定向出芽和核衣壳定向出芽之间的转变。模拟预测糖蛋白定向出芽会导致显著增加的尺寸多分散性和颗粒多态性。这种多分散性可以通过一个理论模型来解释，该模型考虑了膜的弯曲能和糖蛋白壳之间的竞争。模拟还表明，出芽颗粒的几何形状会导致亚基扩散的障碍，从而导致停滞的、部分出芽的状态。我们为这种和其他出芽颗粒的形态提供了一个相图。将这些结构与实验进行比较，可以确定出芽是由糖蛋白还是核衣壳相互作用驱动的。虽然我们的模型是由甲病毒引发的，但我们讨论了我们的结果对其他包膜病毒的影响。
