An anti-CRISPR viral ring nuclease subverts type III CRISPR immunity.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE

Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.

CRISPR-Cas Systems/*immunology ; Endonucleases/*metabolism ; Host Microbial Interactions/*immunology ; Sulfolobus/*virology ; Viral Proteins/*metabolism ; Viruses/*enzymology; Adenine Nucleotides/chemistry ; Adenine Nucleotides/metabolism ; CRISPR-Associated Proteins/chemistry ; CRISPR-Associated Proteins/metabolism ; DNA, Viral/metabolism ; Endonucleases/chemistry ; Models, Molecular ; Nucleotides, Cyclic/chemistry ; Nucleotides, Cyclic/metabolism ; Oligoribonucleotides/chemistry ; Oligoribonucleotides/metabolism ; Phylogeny ; Signal Transduction ; Sulfolobus/genetics ; Sulfolobus/immunology ; Sulfolobus/metabolism ; Viral Proteins/chemistry ; Viral Proteins/classification ; Viruses/immunology

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 domain ⁶ , sculpting a powerful antiviral response ^7-10 that can drive viruses to extinction ^7,8 . Cyclic nucleotides are increasingly implicated in host-pathogen interactions ^11-13 . Here we identify a new family of viral anti-CRISPR (Acr) enzymes that rapidly degrade cyclic tetra-adenylate (cA 4 ). 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 cA 4 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 cA 4 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.

Comment in: Mol Cell. 2020 May 21;78(4):568-569. (PMID: 32442502)

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BB/G011400/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; BB/R008035/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; BB/S000313/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council

0 (Adenine Nucleotides)
0 (CRISPR-Associated Proteins)
0 (DNA, Viral)
0 (Nucleotides, Cyclic)
0 (Oligoribonucleotides)
0 (Viral Proteins)
61172-40-5 (2',5'-oligoadenylate)
EC 3.1.- (Endonucleases)

Date Created: 20200117 Date Completed: 20200507 Latest Revision: 20220715

20221213

PMC6986909

10.1038/s41586-019-1909-5

31942067