CBASS phage defense and evolution of antiviral nucleotide signaling.

Cyclic oligonucleotide-based antiphage signaling system (CBASS) immunity is a widespread form of antiphage defense in bacteria and archaea. Each CBASS operon encodes a cGAS/DncV-like Nucleotidyltransferase (CD-NTase) enzyme that synthesizes a nucleotide second messenger in response to viral infection. An associated Cap effector protein then binds the nucleotide signal and executes cell death to destroy the host cell and block phage propagation. Here we build upon recent advances to establish rules controlling each step of CBASS activation and antiphage defense. Comparative analysis of CBASS, CRISPR, Pycsar, and cGAS-STING immunity provides insight into the evolution of phage defense and animal innate immunity and highlights new questions emerging in the role of nucleotide second messenger signaling in host-virus interactions.