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Updated: Jan 11, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Recurrent acquisition of nuclease-protease pairs in antiviral immunity
Owen T Tuck1,2, Jason J Hu2,3, Santiago C Lopez2
1Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
Abstract:
Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin-like protease repeatedly acquired by multiple, otherwise unrelated antiviral immune systems in bacteria. Cell-based and biochemical assays revealed that the nuclease is a proenzyme that cleaves DNA only after activation by its partner protease. Two distinct immune systems, Hachiman and AVAST (antiviral adenosine triphosphatase/nucleoside triphosphatase of the STAND superfamily, Avs), use the same mechanism of proteolytic activation despite their independent evolutionary origins. Examination of nuclease-protease inheritance patterns identified caspase-nuclease (canu) genomic loci that confer antiviral defense in a pathway reminiscent of eukaryotic caspase activation. These results uncover the coordinated activities of pronucleases and their activating proteases within different immune systems and show how coevolution enables defense system innovation.
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