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Viperin, through its radical‐SAM activity, depletes cellular nucleotide pools and interferes with mitochondrial metabolism to inhibit viral replication
Author(s) -
Ebrahimi Kourosh H.,
Howie Duncan,
Rowbotham Jack S.,
McCullagh James,
Armstrong Fraser A.,
James William S.
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13761
Subject(s) - nucleotide , viral replication , cytidine deaminase , terminator (solar) , cytidine , nucleotide salvage , biology , antiviral protein , mitochondrion , microbiology and biotechnology , chemistry , nucleoside , biochemistry , enzyme , virus , virology , rna , gene , ionosphere , physics , astronomy
Viperin (RSAD2) is an antiviral radical S ‐adenosylmethionine (SAM) enzyme highly expressed in different cell types upon viral infection. Recently, it has been reported that the radical‐SAM activity of viperin transforms cytidine triphosphate (CTP) to its analogue 3′‐deoxy‐3′,4′‐didehydro‐CTP (ddhCTP). Based on biochemical studies and cell biological experiments, it was concluded that ddhCTP and its nucleoside form ddhC do not affect the cellular concentration of nucleotide triphosphates and that ddhCTP acts as replication chain terminator. However, our re‐evaluation of the reported data and new results indicate that ddhCTP is not an effective viral chain terminator but depletes cellular nucleotide pools and interferes with mitochondrial activity to inhibit viral replication. Our analysis is consistent with a unifying view of the antiviral and radical‐SAM activities of viperin.