Group of Computational Biology and Applied Mathematics, Institut de Biologie de l'Ecole Normale Supérieure, Paris, France.
Biophys J. 2012 Mar 7;102(5):980-9. doi: 10.1016/j.bpj.2011.12.037. Epub 2012 Mar 6.
Widely disparate viruses enter the host cell through an endocytic pathway and travel the cytoplasm inside an endosome. For the viral genetic material to be delivered into the cytoplasm, these viruses have to escape the endosomal compartment, an event triggered by the conformational changes of viral endosomolytic proteins. We focus here on small nonenveloped viruses such as adeno-associated viruses, which contain few penetration proteins. The first time a penetration protein changes conformation defines the slowest timescale responsible for the escape. To evaluate this time, we construct what to our knowledge is a novel biophysical model based on a stochastic approach that accounts for the small number of proteins, the endosomal maturation, and the protease activation dynamics. We show that the escape time increases with the endosomal size, whereas decreasing with the number of viral particles inside the endosome. We predict that the optimal escape probability is achieved when the number of proteases in the endosome is in the range of 250-350, achieved for three viral particles.
广泛不同的病毒通过内吞作用途径进入宿主细胞，并在内体内部的细胞质中运输。为了将病毒遗传物质递送到细胞质中，这些病毒必须逃避内体隔室，这一事件是由病毒内溶蛋白的构象变化触发的。我们在这里关注的是小的无包膜病毒，如腺相关病毒，它们只含有少量的穿透蛋白。第一次穿透蛋白发生构象变化定义了负责逃逸的最慢时间尺度。为了评估这个时间，我们构建了一个新颖的基于随机方法的生物物理模型，该模型考虑了蛋白数量少、内体成熟和蛋白酶激活动力学。我们表明，逃逸时间随着内体的大小而增加，而随着内体中病毒颗粒数量的减少而减少。我们预测，当内体中的蛋白酶数量在 250-350 范围内时，逃逸的最佳概率就会达到，这是三个病毒颗粒的情况。
