Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Pantheon Biosciences, Yavne, Israel.
Nature. 2021 Jan;589(7840):120-124. doi: 10.1038/s41586-020-2762-2. Epub 2020 Sep 16.
Viperin is an interferon-induced cellular protein that is conserved in animals. 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. 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.
抗病毒蛋白（Viperin）是一种干扰素诱导的细胞蛋白，在动物中具有保守性。先前的研究表明，它通过产生核苷酸 3'-脱氧-3'，4'-二氢（ddh）-胞苷三磷酸（ddhCTP）来抑制多种病毒的复制，ddhCTP 可作为病毒 RNA 聚合酶的链终止子。在这里，我们表明真核 viperin 起源于一组细菌和古菌蛋白，这些蛋白可抵御噬菌体感染。原核 viperins 产生一组包括 ddhCTP、ddh-鸟苷三磷酸（ddhGTP）和 ddh-尿苷三磷酸（ddhUTP）在内的修饰核苷酸。我们进一步表明，原核 viperins 通过抑制病毒聚合酶依赖性转录来保护细菌免受 T7 噬菌体感染，这表明它具有与动物抗病毒蛋白类似的抗病毒作用机制。我们的研究结果揭示了一类由细菌免疫系统产生的潜在天然抗病毒化合物。
