DNA Tripwire Guards Against Viral Infection

Human cells and bacteria defend against viral infection using signaling proteins named nucleotidyltransferase (NTase) enzymes. Previously, NTase enzymes were known to control antiviral immunity by synthesizing immune signals that act as positive regulators to stimulate downstream immune responses. Kranzusch and Tan’s research now flips this narrative and reveals that NTases in immune systems can restrict viral infection by constitutively synthesizing signals that negatively regulate immune activation. Using structural biology and biochemistry, they discovered a new antiviral defense system in bacterial cells that uses an NTase enzyme to synthesize a DNA signal that binds and represses a partnering protein and thereby functions like a molecular tripwire. During infection, viral proteins cause degradation of the DNA signal, leading to tripwire activation and an immune response that prevents viral propagation.