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.
MeSH terms
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Antiviral Agents / immunology
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Antiviral Agents / metabolism*
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Archaeal Proteins / chemistry
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Archaeal Proteins / metabolism*
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Bacteria / immunology
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Bacteria / metabolism
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Bacteria / virology
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Bacterial Proteins / chemistry
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Bacterial Proteins / metabolism*
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Bacteriophage T7 / enzymology
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Bacteriophage T7 / immunology*
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Bacteriophage T7 / physiology
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DNA-Directed DNA Polymerase / metabolism
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Evolution, Molecular*
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Humans
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Oxidoreductases Acting on CH-CH Group Donors
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Prokaryotic Cells / immunology
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Prokaryotic Cells / metabolism*
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Prokaryotic Cells / virology
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Proteins / chemistry
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Proteins / genetics
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Proteins / metabolism*
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Ribonucleotides / biosynthesis
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Ribonucleotides / chemistry
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Ribonucleotides / metabolism
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Transcription, Genetic / drug effects
Substances
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Antiviral Agents
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Archaeal Proteins
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Bacterial Proteins
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Proteins
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Ribonucleotides
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Oxidoreductases Acting on CH-CH Group Donors
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RSAD2 protein, human
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bacteriophage T7 induced DNA polymerase
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DNA-Directed DNA Polymerase