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Nature ; 589(7840): 120-124, 2021 01.
Article in English | MEDLINE | ID: mdl-32937646

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.


Subject(s)
Antiviral Agents/metabolism , Archaeal Proteins/metabolism , Bacterial Proteins/metabolism , Bacteriophage T7/immunology , Evolution, Molecular , Prokaryotic Cells/metabolism , Proteins/metabolism , Antiviral Agents/immunology , Archaeal Proteins/chemistry , Bacteria/immunology , Bacteria/metabolism , Bacteria/virology , Bacterial Proteins/chemistry , Bacteriophage T7/enzymology , Bacteriophage T7/physiology , DNA-Directed DNA Polymerase/metabolism , Humans , Oxidoreductases Acting on CH-CH Group Donors , Prokaryotic Cells/immunology , Prokaryotic Cells/virology , Proteins/chemistry , Proteins/genetics , Ribonucleotides/biosynthesis , Ribonucleotides/chemistry , Ribonucleotides/metabolism , Transcription, Genetic/drug effects
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