丹麦哥本哈根大学Xu Peng研究团队近期一项研究发现，一个由古细菌病毒所编码的蛋白可抑制III型CRISPR-Cas系统。相关论文2019年9月26日在线发表于国际学术期刊《细胞》。

研究人员报道了由Sulfolobus病毒SIRV2编码的III型CRISPR-Cas抑制剂AcrIIIB1的发现。AcrIIIB1专门抑制由辅助蛋白Csx1的RNA酶活性介导的CRISPR-Cas III-B亚型免疫。AcrIIIB1似乎不与Csx1结合，而是与两种不同的III-B亚型效应物复合物Cmr-α和Cmr-γ相互作用，已知它们响应于原间隔序列转录物的结合而合成了可激活的环状寡聚腺苷酸（cOA），cOA可激活 Csx1的RNA酶活。

因此，研究人员推断AcrIIIB1通过干扰Csx1 RNA酶活相关过程来抑制III-B型CRISPR-Cas免疫。

据介绍，细菌和古细菌具有惊人的CRISPR-Cas系统多样性，可分为六种类型，对病毒感染构成了重大障碍。作为病毒与宿主之间“军备竞赛”的一部分，病毒编码I、II和V型CRISPR-Cas系统的蛋白抑制剂，但是尚不清楚其他机制上不同的CRISPR-Cas类型的天然抑制剂。

附：英文原文

Title: Inhibition of Type III CRISPR-Cas Immunity by an Archaeal Virus-Encoded Anti-CRISPR Protein

Author: Yuvaraj Bhoobalan-Chitty, Thomas Baek Johansen, Nadia Di Cianni, Xu Peng

Issue&Volume: 26 September 2019

Abstract: 

Bacteria and archaea possess a striking diversity of CRISPR-Cas systems divided into six types, posing a significant barrier to viral infection. As part of the virus-host arms race, viruses encode protein inhibitors of type I, II, and V CRISPR-Cas systems, but whether there are natural inhibitors of the other, mechanistically distinct CRISPR-Cas types is unknown. Here, we present the discovery of a type III CRISPR-Cas inhibitor, AcrIIIB1, encoded by the Sulfolobus virus SIRV2. AcrIIIB1 exclusively inhibits CRISPR-Cas subtype III-B immunity mediated by the RNase activity of the accessory protein Csx1. AcrIIIB1 does not appear to bind Csx1 but, rather, interacts with two distinct subtype III-B effector complexes—Cmr-α and Cmr-γ—which, in response to protospacer transcript binding, are known to synthesize cyclic oligoadenylates (cOAs) that activate the Csx1 “collateral” RNase. Taken together, we infer that AcrIIIB1 inhibits type III-B CRISPR-Cas immunity by interfering with a Csx1 RNase-related process.

DOI: 10.1016/j.cell.2019.09.003

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31009-8