Hochhauser Dina, Sorek Rotem
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Nat Rev Immunol. 2025 Jul 29. doi: 10.1038/s41577-025-01206-w.
The cell-autonomous innate immune system is responsible for sensing and mitigating viral infection at the level of individual cells. Many of the mechanisms used by the cell-autonomous innate immune system in eukaryotic cells are ancient and have evolutionary roots in bacterial systems that defend against phage infection. Studies from recent years have shown that modification of the free nucleotide pool is central to many of these conserved immune mechanisms. In this Review, we explain how immune pathways manipulate the available pool of nucleotides to deprive viruses of molecules essential for their replication, how immune proteins chemically modify nucleotides to generate immune signalling molecules, and how cell-autonomous innate immune mechanisms produce altered nucleotides that poison viral replication. We also discuss the mechanisms used by viruses to antagonize nucleotide-based immunity. Finally, we explore the evolutionary logic of using nucleotides as building blocks for immune responses.
细胞自主的固有免疫系统负责在单个细胞水平上感知和减轻病毒感染。真核细胞中细胞自主的固有免疫系统所使用的许多机制都很古老，并且在抵御噬菌体感染的细菌系统中有着进化根源。近年来的研究表明，游离核苷酸库的修饰是许多这些保守免疫机制的核心。在本综述中，我们解释了免疫途径如何操纵可用的核苷酸库以剥夺病毒复制所需的分子，免疫蛋白如何对核苷酸进行化学修饰以产生免疫信号分子，以及细胞自主的固有免疫机制如何产生改变的核苷酸来毒害病毒复制。我们还讨论了病毒用于对抗基于核苷酸的免疫的机制。最后，我们探讨了使用核苷酸作为免疫反应构件的进化逻辑。
