Prokaryotic viperins produce diverse antiviral molecules

Aude Bernheim, Adi Jenny Millman Dayan, Gal Ofir, Gilad Meitav, Carmel Avraham, Helena Shomar, Masha M. Rosenberg, Nir Tal, Sarah Melamed, Gil Amitai, Rotem Sorek

Research output: Contribution to journalArticlepeer-review


Viperin is an interferon-induced cellular protein that is conserved in animals 1. It has previously been shown to inhibit the replication of multiple viruses by producing the ribonucleotide 3′-deoxy-3′,4′-didehydro (ddh)-cytidine triphosphate (ddhCTP), which acts as a chain terminator for viral RNA polymerase 2. Here we show that eukaryotic viperin originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins produce a set of modified ribonucleotides that include ddhCTP, ddh-guanosine triphosphate (ddhGTP) and ddh-uridine triphosphate (ddhUTP). We further show that prokaryotic viperins protect against T7 phage infection by inhibiting viral polymerase-dependent transcription, suggesting that it has an antiviral mechanism of action similar to that of animal viperin. Our results reveal a class of potential natural antiviral compounds produced by bacterial immune systems.

Original languageEnglish
Pages (from-to)120-124
Number of pages5
Issue number7840
Early online date16 Sep 2020
StatePublished - 7 Jan 2021


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