Mas Vicente, Melero Jose Antonio
Unidad de Biología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Subcell Biochem. 2024;105:567-592. doi: 10.1007/978-3-031-65187-8_16.
Viruses are intracellular parasites that hijack the cellular machinery for their own replication. Therefore, an obligatory step in the virus life cycle is the delivery of the viral genome inside the cell. Enveloped viruses (i.e., viruses with a lipid envelope) use a two-step procedure to release their genetic material into the cell: (1) they first bind to specific surface receptors of the target cell membrane and then (2) they fuse the viral and cell membranes. This last step may occur at the cell surface or after internalization of the virus particle by endocytosis or by some other route (e.g., macropinocytosis). Remarkably, the virus-cell membrane fusion process goes essentially along the same intermediate steps than other membrane fusions that occur, for instance, in vesicular fusion at the nerve synapsis or cell-cell fusion in yeast mating. Specialized viral proteins, fusogens, promote virus-cell membrane fusion. The viral fusogens experience drastic structural rearrangements during fusion, releasing the energy required to overcome the repulsive forces that prevent spontaneous fusion of the two membranes. This chapter provides an overview of the different types of viral fusogens and their mode of action, as they are currently known. Furthermore, it outlines novel strategies for vaccine development related to stabilized viral fusogens.
病毒是细胞内寄生虫，它们劫持细胞机制以进行自身复制。因此，病毒生命周期中的一个必要步骤是将病毒基因组递送至细胞内部。包膜病毒（即具有脂质包膜的病毒）采用两步程序将其遗传物质释放到细胞中：（1）它们首先与靶细胞膜的特定表面受体结合，然后（2）使病毒膜与细胞膜融合。最后这一步可能发生在细胞表面，或者在病毒颗粒通过内吞作用或其他途径（例如巨胞饮作用）内化之后。值得注意的是，病毒 - 细胞膜融合过程基本上与其他膜融合过程沿着相同的中间步骤进行，例如在神经突触处的囊泡融合或酵母交配中的细胞 - 细胞融合。专门的病毒蛋白，即融合蛋白，促进病毒 - 细胞膜融合。病毒融合蛋白在融合过程中经历剧烈的结构重排，释放出克服阻止两个膜自发融合的排斥力所需的能量。本章概述了目前已知的不同类型的病毒融合蛋白及其作用方式。此外，它还概述了与稳定化病毒融合蛋白相关的疫苗开发新策略。
