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Prokaryotic viperins produce diverse antiviral molecules.

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.

SUBMITTER: Bernheim A

PROVIDER: S-EPMC7610908 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Prokaryotic viperins produce diverse antiviral molecules.

Bernheim Aude A Millman Adi A Ofir Gal G Meitav Gilad G Avraham Carmel C Shomar Helena H Rosenberg Masha M MM Tal Nir N Melamed Sarah S Amitai Gil G Sorek Rotem R

Nature 20200916 7840

Viperin is an interferon-induced cellular protein that is conserved in animals<sup>1</sup>. 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<sup>2</sup>. Here we show that eukaryotic viperin originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins produce a s ...[more]

PMID: 32937646

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Prokaryotic viperins produce diverse antiviral molecules

Project description:Discovery of the anti-phage activity of prokaryotic viperins

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Prokaryotic viperins produce diverse antiviral molecules

Project description:Viperin is an interferon-induced cellular protein conserved in animals. It was shown to inhibit the replication of multiple viruses by producing a ribonucleotide called 3’-deoxy-3’4’-didehydro-CTP (ddhCTP), which acts as a chain terminator for the viral RNA polymerase. Here we show that the eukaryotic viperin has originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins (pVips) produce a set of modified ribonucleotides that include, in addition to ddhCTP, also ddhGTP and ddhUTP. We further provide evidence that pVips protect against T7 phage infection by inhibiting viral polymerase-dependent transcription, suggesting a conserved mechanism of action shared between pVips and the animal viperin. Our results unveil a potential repository of natural antiviral compounds produced by bacterial immune systems.

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