美国蒙大拿大学Blake Wiedenheft和法国巴黎城市大学David Bikard团队共同合作，近期取得重要工作进展。他们研究发现，病毒编码的tRNA中和了PARIS抗病毒防御系统。相关研究成果2024年8月7日在线发表于《自然》杂志上。

据介绍，病毒相互竞争有限的细胞资源，有些病毒提供防御机制，保护宿主免受竞争性遗传寄生虫的侵害。PARIS是一种防御系统，通常编码在病毒基因组中，由55 kDa的ABC ATP酶（AriA）和35 kDa的TOPRIM核酸酶（AriB）组成。然而，AriA和AriB在噬菌体防御中的作用机制尚不清楚。

研究人员表明AriA和AriB组装成425 kDa的超分子免疫复合物。基于冷冻电镜的复合物结构分析，解释了AriA的六个分子如何组装成一个螺旋桨形的支架。该支架协调AriB的三个亚基。ATP依赖性检测外源蛋白会触发AriB的释放，AriB组装成一种同二聚核酸酶，通过切割宿主tRNA^Lys来阻断感染。噬菌体T5通过表达不被PARIS切割的tRNA^Lys变体来破坏PARIS免疫，从而恢复病毒感染。

总之，这一研究解释了AriA如何作为检测病毒蛋白并激活AriB毒素的ATP依赖性传感器发挥作用。PARIS是一组新兴的免疫系统之一，它们形成大分子复合物来识别外来蛋白质，而不是外来核酸。

附：英文原文

Title: A virally-encoded tRNA neutralizes the PARIS antiviral defence system

Author: Burman, Nathaniel, Belukhina, Svetlana, Depardieu, Florence, Wilkinson, Royce A., Skutel, Mikhail, Santiago-Frangos, Andrew, Graham, Ava B., Livenskyi, Alexei, Chechenina, Anna, Morozova, Natalia, Zahl, Trevor, Henriques, William S., Buyukyoruk, Murat, Rouillon, Christophe, Saudemont, Baptiste, Shyrokova, Lena, Kurata, Tatsuaki, Hauryliuk, Vasili, Severinov, Konstantin, Groseille, Justine, Thierry, Agns, Koszul, Romain, Tesson, Florian, Bernheim, Aude, Bikard, David, Wiedenheft, Blake, Isaev, Artem

Issue&Volume: 2024-08-07

Abstract: Viruses compete with each other for limited cellular resources, and some deliver defense mechanisms that protect the host from competing genetic parasites1. PARIS is a defense system, often encoded in viral genomes, that is composed of a 55kDa ABC ATPase (AriA) and a 35kDa TOPRIM nuclease (AriB)2. However, the mechanism by which AriA and AriB function in phage defense is unknown. Here we show that AriA and AriB assemble into a 425kDa supramolecular immune complex. We use cryo-EM to determine the structure of this complex which explains how six molecules of AriA assemble into a propeller-shaped scaffold that coordinates three subunits of AriB. ATP-dependent detection of foreign proteins triggers the release of AriB, which assembles into a homodimeric nuclease that blocks infection by cleaving host tRNALys. Phage T5 subverts PARIS immunity through expression of a tRNALys variant that is not cleaved by PARIS, and thereby restores viral infection. Collectively, these data explain how AriA functions as an ATP-dependent sensor that detects viral proteins and activates the AriB toxin. PARIS is one of an emerging set of immune systems that form macromolecular complexes for the recognition of foreign proteins, rather than foreign nucleic acids3.

DOI: 10.1038/s41586-024-07874-3

Source: https://www.nature.com/articles/s41586-024-07874-3