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

Cell. 2019 Oct 3;179(2):448-458.e11. doi: 10.1016/j.cell.2019.09.003. Epub 2019 Sep 26.


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.

Keywords: AcrIIIB; CRISPR-Cas type III accessory RNase; Cmr; Cmr2 (Cas10); anti-CRISPR; cell dormancy; collateral RNA degradation; middle/late viral genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Associated Proteins / physiology*
  • CRISPR-Cas Systems*
  • Host-Pathogen Interactions*
  • Ribonucleases / metabolism
  • Rudiviridae / metabolism*
  • Sulfolobus / virology*


  • CRISPR-Associated Proteins
  • Ribonucleases