School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
J Biol Chem. 2021 Jul;297(1):100856. doi: 10.1016/j.jbc.2021.100856. Epub 2021 Jun 29.
The nuclear pore complex is the sole gateway connecting the nucleoplasm and cytoplasm. In humans, the nuclear pore complex is one of the largest multiprotein assemblies in the cell, with a molecular mass of ∼110 MDa and consisting of 8 to 64 copies of about 34 different nuclear pore proteins, termed nucleoporins, for a total of 1000 subunits per pore. Trafficking events across the nuclear pore are mediated by nuclear transport receptors and are highly regulated. The nuclear pore complex is also used by several RNA viruses and almost all DNA viruses to access the host cell nucleoplasm for replication. Viruses hijack the nuclear pore complex, and nuclear transport receptors, to access the nucleoplasm where they replicate. In addition, the nuclear pore complex is used by the cell innate immune system, a network of signal transduction pathways that coordinates the first response to foreign invaders, including viruses and other pathogens. Several branches of this response depend on dynamic signaling events that involve the nuclear translocation of downstream signal transducers. Mounting evidence has shown that these signaling cascades, especially those steps that involve nucleocytoplasmic trafficking events, are targeted by viruses so that they can evade the innate immune system. This review summarizes how nuclear pore proteins and nuclear transport receptors contribute to the innate immune response and highlights how viruses manipulate this cellular machinery to favor infection. A comprehensive understanding of nuclear pore proteins in antiviral innate immunity will likely contribute to the development of new antiviral therapeutic strategies.
核孔复合体是连接核质和细胞质的唯一通道。在人类中，核孔复合体是细胞中最大的多蛋白组装体之一，分子量约为 110 MDa，由 8 到 64 个约 34 种不同的核孔蛋白组成，称为核孔蛋白，每个核孔有 1000 个亚基。核孔的转运事件由核转运受体介导，并受到高度调控。核孔复合体也被几种 RNA 病毒和几乎所有的 DNA 病毒用来进入宿主细胞的核质进行复制。病毒劫持核孔复合体和核转运受体来进入核质，在那里它们进行复制。此外，核孔复合体被细胞先天免疫系统利用，先天免疫系统是一个信号转导途径的网络，协调对外来入侵者（包括病毒和其他病原体）的第一反应。这个反应的几个分支依赖于涉及下游信号转导物核易位的动态信号事件。越来越多的证据表明，这些信号级联反应，特别是那些涉及核质转运事件的步骤，是被病毒靶向的，以便它们可以逃避先天免疫系统。这篇综述总结了核孔蛋白和核转运受体如何促进先天免疫反应，并强调了病毒如何操纵这种细胞机制来促进感染。全面了解抗病毒先天免疫中的核孔蛋白可能有助于开发新的抗病毒治疗策略。
