A viral ring nuclease anti-CRISPR subverts type III CRISPR immunity

The CRISPR system in bacteria and archaea provides adaptive immunity against mobile genetic elements. Type III CRISPR systems detect viral RNA, resulting in the activation of two regions of the Cas10 protein: an HD nuclease domain (which degrades viral DNA)1,2 and a cyclase domain (which synthesizes cyclic oligoadenylates from ATP)3–5. Cyclic oligoadenylates in turn activate defence enzymes with a CRISPR-associated Rossmann fold domain6, sculpting a powerful antiviral response7–10 that can drive viruses to extinction7,8. Cyclic nucleotides are increasingly implicated in host–pathogen interactions11–13. Here we identify a new family of viral anti-CRISPR (Acr) enzymes that rapidly degrade cyclic tetra-adenylate (cA4). The viral ring nuclease AcrIII-1 is widely distributed in archaeal and bacterial viruses and in proviruses. The enzyme uses a previously unknown fold to bind cA4 specifically, and a conserved active site to rapidly cleave this signalling molecule, allowing viruses to neutralize the type III CRISPR defence system. The AcrIII-1 family has a broad host range, as it targets cA4 signalling molecules rather than specific CRISPR effector proteins. Our findings highlight the crucial role of cyclic nucleotide signalling in the conflict between viruses and their hosts. Bacteria and archaea use cyclic oligoadenylate molecules as part of the CRISPR system for antiviral defence; here, a family of viral enzymes that rapidly degrades cyclic oligoadenylates is identified and biochemically and structurally described.

• Publication year

  2019

• Venue

  Nature

• Publication date

  2019-09-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/s41586-019-1909-5PMID 31942067PMCID 6986909
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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