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基于细菌TIR的免疫系统感知到病毒囊,从而启动防御

Cameron G Roberts¹, Chloe B Fishman¹, Dalton V Banh^1,2

¹Laboratory of Bacteriology, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.

bioRxiv : the preprint server for biology

|August 12, 2024

概括

细菌免疫系统使用Toll/interleukin-1受体 (TIR) 域来检测菌体感染. 托瑞斯系统感知了菌囊蛋白,触发了防御,通过耗尽NAD+来限制病毒传播.

科学领域:

微生物学微生物学
免疫学免疫学免疫学
病毒学病毒学

背景情况:

Prokaryotic 免疫系统,包括具有 Toll/interleukin-1 受体 (TIR) 域的免疫系统,对病毒 (菌体) 感染进行防御.
TIR域可以产生周期性腺二酸盐-核糖 (ADPR) 来激活耗尽NAD+的效应因子,限制菌体的传播.

研究的目的:

阐明细菌TIR域识别菌体感染的感应机制.
为了描述葡萄球菌Thoeris防御系统与菌体组件的相互作用.

主要方法:

研究了葡萄球菌Thoeris的防御系统,包括ThsB1,ThsB2 (TIR传感器) 和ThsA (效应器).
分析了菌体F80α大囊蛋白与ThsB1/ThsB2.2之间的相互作用.
评估了1′-3′糖循环ADPR (gcADPR) 和NAD+裂变激活的合成.
检查了菌体囊蛋白中的突变,这些突变赋予了对Thoeris免疫力的抵抗力.
通过ThsB1/B2.2.测试了葡萄球菌Sifhoviridae囊蛋白的识别.

主要成果:

菌体 Φ80α 的主要囊蛋白与 ThsB1 和 ThsB2.2 形成一个复合体.
这种复杂的形成足以进行gcADPR合成和随后激活ThsA介导的NAD+裂变.
避开托埃里斯免疫力的菌体具有囊突变,防止这种复杂的形成.
ThsB1/B2 特别识别了葡萄球菌Sifhoviridae B血清组的囊蛋白,但不是A血清组.

结论:

葡萄球菌Thoeris系统通过其TIR域传感器直接识别囊蛋白来感知菌体感染.
这种囊体识别机制对于激活先天抗病毒防御至关重要,并可能推动病毒进化.
这些发现表明,先天抗病毒防御激活的保护机制,并行哺乳动物收费类受体通路.

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