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bioRxiv · 10.1101/778746

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

Athukoralage, J. S.·McMahon, S.·Zhang, C.·Gruschow, S.·Graham, S.·Krupovic, M.·Whitaker, R. J.·Gloster, T.·White, M. F.
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Abstract

The CRISPR system provides adaptive immunity against mobile genetic elements in bacteria and archaea. On detection of viral RNA, type III CRISPR systems generate a cyclic oligoadenylate (cOA) second messenger1-3, activating defence enzymes and sculpting a powerful antiviral response that can drive viruses to extinction4,5. Cyclic nucleotides are increasingly implicated as playing an important role in host-pathogen interactions6,7. Here, we identify a widespread new family of viral anti-CRISPR (Acr) enzymes that rapidly degrade cyclic tetra-adenylate (cA4). The viral ring nuclease (AcrIII-1) is the first Acr described for type III CRISPR systems and is widely distributed in archaeal and bacterial viruses, and proviruses. The enzyme uses a novel fold to bind cA4 specifically and utilizes a conserved active site to rapidly cleave the signalling molecule, allowing viruses to neutralise 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. This study highlights the crucial role of cyclic nucleotide signalling in the conflict between viruses and their hosts.

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Athukoralage, J. S., McMahon, S., Zhang, C., Gruschow, S., Graham, S., Krupovic, M., Whitaker, R. J., Gloster, T., White, M. F.. 2019-09-24. A viral ring nuclease anti-CRISPR subverts type III CRISPR immunity. https://doi.org/10.1101/778746

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