Department Chemistry, University of Oxford, UK.
Sir William Dunn School of Pathology, University of Oxford, UK.
FEBS Lett. 2020 May;594(10):1624-1630. doi: 10.1002/1873-3468.13761. Epub 2020 Mar 2.
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.
抗病毒蛋白 Viperin（RSAD2）是一种在病毒感染不同细胞类型时高度表达的抗病毒自由基 S-腺苷甲硫氨酸（SAM）酶。最近，有报道称，Viperin 的自由基-SAM 活性将胞苷三磷酸（CTP）转化为其类似物 3'-脱氧-3',4'-二氢-CTP（ddhCTP）。基于生化研究和细胞生物学实验，得出结论认为 ddhCTP 及其核苷形式 ddhC 不会影响核苷酸三磷酸的细胞浓度，并且 ddhCTP 作为复制链终止子发挥作用。然而，我们对报告数据的重新评估和新结果表明，ddhCTP 不是有效的病毒链终止子，而是耗尽细胞核苷酸池并干扰线粒体活性以抑制病毒复制。我们的分析与抗病毒蛋白 Viperin 的抗病毒和自由基-SAM 活性的统一观点一致。
