Discovery of the anti-phage activity of prokaryotic viperins. Prokaryotic viperins produce diverse antiviral molecules

Viperin is an interferon-induced cellular protein that is conserved in animals. It was shown toinhibit the replication of multiple viruses by producing a ribonucleotide called ddhCTP thatacts as a chain terminator for the viral RNA polymerase. Here we show that the evolutionaryorigin of the eukaryotic viperin stems from a clade of bacterial and archaeal proteins thatprotect from phage infection. Prokaryotic viperins (pVips) produce a set of modifiedribonucleotides that include, in addition to ddhCTP, also ddhGTP and ddhUTP. We furtherprovide evidence that pVips protect against T7 phage infection by inhibiting viralpolymerase-dependent transcription, suggesting a conserved mechanism of action sharedbetween pVips and the animal viperin. Our results unveil a potential repository of naturalantiviral compounds produced by bacterial immune systems.