Bacterial origins of cyclic nucleotide-activated antiviral immune signaling.
Bacterial origins of cyclic nucleotide-activated antiviral immune signaling.
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DOI：
10.1016/j.molcel.2022.11.006
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发表时间：
2022-11
期刊：
影响因子：
16
通讯作者：
D. Patel;You Yu;N. Jia
中科院分区：
文献类型：
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作者：
D. Patel;You Yu;N. Jia
由不同碱基、环大小和 3'-5'/2'-5' 连接组合组成的环状寡核苷酸 (cO) 介导的第二信使信号传导构成了导致信号通路激活的初始触发因素，从而影响针对入侵病毒和噬菌体的免疫介导的抗病毒防御。细菌和古细菌已经进化出了 CRISPR、CBASS、Pycsar 和 Thoeris 监视复合体，这些复合体涉及 cO 介导的效应器激活，通过靶向核酸酶活性、效应器寡聚化介导的必需细胞代谢物的消耗或宿主细胞膜功能的破坏来实现抗病毒防御。值得注意的是，抗病毒防御利用了流产感染机制，即受感染的细胞在噬菌体复制周期完成之前死亡。反过来，噬菌体进化出了一些小蛋白质，这些蛋白质可以靶向并降解/隔离 cO，从而抑制宿主免疫。这篇综述提出了基于结构的机制视角，介绍了CO介导的抗病毒防御领域的最新进展，特别强调了后生动物对细菌细胞自主先天免疫机制的古老进化适应。
Second-messenger-mediated signaling by cyclic oligonucleotides (cOs) composed of distinct base, ring size, and 3′-5′/2′-5′ linkage combinations constitutes the initial trigger resulting in activation of signaling pathways that have an impact on immune-mediated antiviral defense against invading viruses and phages. Bacteria and archaea have evolved CRISPR, CBASS, Pycsar, and Thoeris surveillance complexes that involve cO-mediated activation of effectors resulting in antiviral defense through either targeted nuclease activity, effector oligomerization-mediated depletion of essential cellular metabolites or disruption of host cell membrane functions. Notably, antiviral defense capitalizes on an abortive infection mechanism, whereby infected cells die prior to completion of the phage replication cycle. In turn, phages have evolved small proteins that target and degrade/sequester cOs, thereby suppressing host immunity. This review presents a structure-based mechanistic perspective of recent advances in the field of cO-mediated antiviral defense, in particular highlighting the ancient evolutionary adaptation by metazoans of bacterial cell-autonomous innate immune mechanisms.