Anti-CRISPR Proteins in Archaea.

Anti-CRISPR (Acr) proteins are natural inhibitors of CRISPR-Cas immune systems. To date, Acrs inhibiting types I, II, III, V, and VI CRISPR-Cas systems have been characterized. While most known Acrs are derived from bacterial phages and prophages, very few have been characterized in the domain Archaea, despite the nearly ubiquitous presence of CRISPR-Cas in archaeal cells. Here we summarize the discovery and characterization of the archaeal Acrs with the representatives encoded by a model archaeal virus, Sulfolobus islandicus rod-shaped virus 2 (SIRV2). AcrID1 inhibits subtype I-D CRISPR-Cas immunity through direct interaction with the large subunit Cas10d of the effector complex, and AcrIIIB1 inhibits subtype III-B CRISPR-Cas immunity through a mechanism interfering with middle/late gene targeting. Future development of efficient screening methods will be key to uncovering the diversity of archaeal Acrs. Similar to bacterial viruses, archaeal viruses encode anti-CRISPR (Acr) proteins. The known archaeal acrs are found in variable regions of viral genomes and are easily lost in the absence of evolutionary pressure. Two Acrs, AcrID1 and AcrIIIB1, have been identified from SIRV2. AcrID1 interacts with the large subunit of the type I-D effector complex Cas10d. AcrID1 is found in multiple copies of low similarity in individual viruses, up to 12 homologs in SIRV2, a phenomenon that has not been observed with bacterial Acrs. AcrIIIB1 inhibits subtype III-B CRISPR-Cas immunity by interfering with middle/late gene targeting. In correlation to the lower abundance of subtype I-D systems in comparison with the wide distribution of subtype III-B systems in archaea, AcrID1 is restricted to fewer viruses while AcrIIIB1 is more widespread. [ABSTRACT FROM AUTHOR]