Department of Biological Sciences, Purdue University, 240 S. Martin Jischke Drive, West Lafayette, IN, United States.
Department of Biological Sciences, Purdue University, 240 S. Martin Jischke Drive, West Lafayette, IN, United States.
J Struct Biol. 2014 Jan;185(1):27-31. doi: 10.1016/j.jsb.2013.11.001. Epub 2013 Nov 16.
Flaviviruses, such as dengue, West Nile, and yellow fever viruses, assemble as fusion-incompetent particles and subsequently undergo a large reorganization of their glycoprotein envelope resulting in formation of mature infectious virions. Here we used a combination of three-dimensional cryo-electron tomography and two-dimensional image analysis to study pleomorphic maturation intermediates of dengue virus 2. Icosahedral symmetries of immature and mature regions within one particle were mismatched relative to each other. Furthermore, the orientation of the two regions relative to each other differed among particles. Therefore, there cannot be a specific pathway determining the maturation of all particles. Instead, the region with mature structure expands when glycoproteins on its boundary acquire suitable orientation and conformation to allow them to become a stable part of the mature region. This type of maturation is possible because the envelope glycoproteins are anchored to the phospholipid bilayer that is a part of flavivirus virions and are thus restricted to movement on the two-dimensional surface of the particle. Therefore, compounds that limit movement of the glycoproteins within the virus membrane might be used as inhibitors of flavivirus maturation.
黄病毒（如登革热、西尼罗河和黄热病病毒）作为融合缺陷颗粒组装，随后其糖蛋白包膜发生大规模重排，导致成熟感染性病毒颗粒的形成。在这里，我们使用三维冷冻电子断层扫描和二维图像分析的组合来研究登革热病毒 2 的多形性成熟中间产物。相对于彼此，一个颗粒内未成熟和成熟区域的二十面体对称性不匹配。此外，两个区域相对于彼此的取向在颗粒之间也不同。因此，不可能有一个特定的途径来决定所有颗粒的成熟。相反，当边界上的糖蛋白获得合适的方向和构象以允许它们成为成熟区域的稳定部分时，具有成熟结构的区域会扩展。这种类型的成熟是可能的，因为包膜糖蛋白锚定在磷脂双层上，磷脂双层是黄病毒病毒粒子的一部分，因此只能在粒子的二维表面上移动。因此，限制糖蛋白在病毒膜内运动的化合物可能被用作黄病毒成熟的抑制剂。
