美国洛克菲勒大学Luciano A. Marraffini和美国纪念斯隆·凯特琳癌症中心Dinshaw J. Patel研究团队合作取得新进展。他们的最新研究提出噬菌体编码的抗CRISPR可完全逃逸VI-A型CRISPR-Cas免疫。最新成果发表在2020年5月28日出版的《科学》杂志上。

他们描述了一种编码抗CRISPR蛋白（AcrVIA1）的李斯特菌噬菌（?LS46），该蛋白可以灭活李斯特菌的VI-A CRISPR系统。 利用遗传学、生物化学和结构生物学方法，他们发现AcrVIA1与Cas13a的引导接触表面相互作用，从而阻止了靠近靶RNA以及核酸酶激活所需的构象变化。

不同于DNA切割Cas核酸酶的抑制剂，其会导致有限的免疫抑制并需要多次感染才能绕过CRISPR防御，单个病毒体递送的单剂量AcrVIA1可以完全消除VI-A CRISPR介导的免疫力。

据了解，crRNA引导的核酸酶Cas13识别互补的病毒转录本，以在VI型CRISPR-Cas抗病毒反应期间触发宿主和病毒RNA的降解。病毒如何抵消这种免疫力尚不清楚。

附：英文原文

Title: A phage-encoded anti-CRISPR enables complete evasion of type VI-A CRISPR-Cas immunity

Author: Alexander J. Meeske, Ning Jia, Alice K. Cassel, Albina Kozlova, Jingqiu Liao, Martin Wiedmann, Dinshaw J. Patel, Luciano A. Marraffini

Issue&Volume: 2020/05/28

Abstract: Abstract The crRNA-guided nuclease Cas13 recognizes complementary viral transcripts to trigger the degradation of both host and viral RNA during the type VI CRISPR-Cas antiviral response. How viruses can counteract this immunity is not known. We describe a listeriophage (LS46) encoding an anti-CRISPR protein (AcrVIA1) that inactivated the type VI-A CRISPR system of Listeria seeligeri. Using genetics, biochemistry and structural biology we found that AcrVIA1 interacted with the guide-exposed face of Cas13a, preventing access to the target RNA and the conformational changes required for nuclease activation. Unlike inhibitors of DNA-cleaving Cas nucleases, which cause limited immunosuppression and require multiple infections to bypass CRISPR defenses, a single dose of AcrVIA1 delivered by an individual virion could completely dismantle type VI-A CRISPR-mediated immunity.

DOI: 10.1126/science.abb6151

Source: https://science.sciencemag.org/content/early/2020/05/27/science.abb6151