This research identifies and validates new families of phage-encoded antidefense proteins that allow viruses to bypass bacterial innate immunity. By analyzing common structural traits, researchers developed a computational pipeline to discover viral proteins that either sequester or enzymatically degrade nucleotide signaling molecules. This approach led to the identification of Sequestin and Lockin, two "sponge" protein families that neutralize the Thoeris defense system, and Acb5, an enzyme that disables CBASS immunity. Structural modeling and biochemical assays confirmed that these proteins are widespread in nature, appearing in thousands of viral genomes including the well-studied T4 phage. The study demonstrates that structure-guided discovery is a powerful method for uncovering the diverse strategies viruses use to subvert host immune signaling across different domains of life.

References:

• Tal N, Hadary R, Chang R B, et al. Structural modeling reveals phage proteins that manipulate bacterial immune signaling[J]. Science, 2026, 391(6789): eaea1761.