Cyclic Nucleotide Signaling in Phage Defense and Counter-Defense
Cyclic Nucleotide Signaling in Phage Defense and Counter-Defense
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DOI：
10.1146/annurev-virology-100120-010228
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发表时间：
2022-01-01
影响因子：
11.3
通讯作者：
White, Malcolm F.
中科院分区：
文献类型：
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作者：
Athukoralage, Januka S.;White, Malcolm F.
过去几年，我们对原核抗噬菌体防御机制的理解取得了进展，揭示了许多新的环核苷酸信号分子，它们在将受感染的细胞转变为抗病毒状态方面发挥着至关重要的作用。防御途径包括 III 型 CRISPR（成簇规则间隔回文重复序列）、CBASS（基于环核苷酸的抗噬菌体信号系统）、PYCSAR（用于抗噬菌体抗性的嘧啶环化酶系统）和 Thoeris 都使用环核苷酸作为第二信使来激活多种效应蛋白。这些效应物通常会降解或破坏关键的细胞成分，例如核酸、细胞膜或代谢物，从而减慢病毒复制动力学，给受感染的细胞带来巨大的代价。细胞利用操纵环核苷酸水平的机制来调节防御途径，病毒利用机制来破坏它们。在这里，我们回顾了关键通路、信号分子和效应器的发现和机制、系统之间的相似之处和差异、悬而未决的问题以及该领域未来研究的前景。
Advances in our understanding of prokaryotic antiphage defense mechanisms in the past few years have revealed a multitude of new cyclic nucleotide signaling molecules that play a crucial role in switching infected cells into an antiviral state. Defense pathways including type III CRISPR (clustered regularly interspaced palindromic repeats), CBASS (cyclic nucleotide-based antiphage signaling system), PYCSAR (pyrimidine cyclase system for antiphage resistance), and Thoeris all use cyclic nucleotides as second messengers to activate a diverse range of effector proteins. These effectors typically degrade or disrupt key cellular components such as nucleic acids, membranes, or metabolites, slowing down viral replication kinetics at great cost to the infected cell. Mechanisms to manipulate the levels of cyclic nucleotides are employed by cells to regulate defense pathways and by viruses to subvert them. Here we review the discovery and mechanism of the key pathways, signaling molecules and effectors, parallels and differences between the systems, open questions, and prospects for future research in this area.