Prokaryotic viperins produce diverse antiviral molecules

Aude Bernheim, Adi Millman, Gal Ofir, Gilad Meitav, Carmel Avraham, Helena Shomar, Masha M. Rosenberg, Nir Tal, Sarah Melamed, Gil Amitai and Rotem Sorek ()
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Aude Bernheim: Weizmann Institute of Science
Adi Millman: Weizmann Institute of Science
Gal Ofir: Weizmann Institute of Science
Gilad Meitav: Weizmann Institute of Science
Carmel Avraham: Weizmann Institute of Science
Helena Shomar: Pantheon Biosciences
Masha M. Rosenberg: Pantheon Biosciences
Nir Tal: Pantheon Biosciences
Sarah Melamed: Weizmann Institute of Science
Gil Amitai: Weizmann Institute of Science
Rotem Sorek: Weizmann Institute of Science

Nature, 2021, vol. 589, issue 7840, 120-124

Abstract: Abstract Viperin is an interferon-induced cellular protein that is conserved in animals1. 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 polymerase2. 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.

Date: 2021
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DOI: 10.1038/s41586-020-2762-2

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