@article{0c8c6e91717143008c60e0f7f1a78b57,
title = "Prokaryotic viperins produce diverse antiviral molecules",
abstract = "Viperin is an interferon-induced cellular protein that is conserved in animals 1. 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 2. 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.",
author = "Aude Bernheim and {Millman Dayan}, {Adi Jenny} and Gal Ofir and Gilad Meitav and Carmel Avraham and Helena Shomar and Rosenberg, {Masha M.} and Nir Tal and Sarah Melamed and Gil Amitai and Rotem Sorek",
note = "We thank Morten Danielsen and Daniel Malheiro from MS-omics (Denmark) for conducting the MS experiments and for the extensive help with the data analysis. We also thank the Sorek laboratory members for comments on earlier versions of this manuscript. A.B. is the recipient of a European Molecular Biology Organization (EMBO) Long Term Fellowship (EMBO ALTF 186-2018). A.M. was supported by a fellowship from the Ariane de Rothschild Women Doctoral Program and, in part, by the Israeli Council for Higher Education via the Weizmann Data Science Research Center. G.O. was supported by the Weizmann Sustainability and Energy Research Initiative (SAERI) doctoral fellowship. R.S. was supported, in part, by the Israel Science Foundation (personal grant 1360/16), the European Research Council (grant ERC-CoG 681203), the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, the Minerva Foundation with funding from the Federal German Ministry for Education and Research, the Ben B. and Joyce E. Eisenberg Foundation, and the Knell Family Center for Microbiology. Author contributions: A.B. and R.S. led the study and A.B. performed all experiments unless otherwise indicated. A.M. and A.B performed the computational analyses that appear in Figs. 1 and 2 and Extended Data Fig 9. H.S., M.R. and N.T. designed and performed purification of pVips and in vitro enzymatic assays that appear in Fig. 3 and Extended Data Fig 6. G.M., C.A, and S.M. assisted with the plaque assays that appear in Fig. 1 and Extended Data Fig. 1. C.A. assisted in the preparation of cell lysates that appear in Fig. 3 and Extended Data Figs 3, 4 and 5. G.O and G.A assisted in the design and analysis of GFP reporting studies presented in Fig 4 and Extended Data Fig 7. R.S. supervised the study. R.S and A.B. wrote the paper together with the team.",
year = "2021",
month = jan,
day = "7",
doi = "https://doi.org/10.1038/s41586-020-2762-2",
language = "الإنجليزيّة",
volume = "589",
pages = "120--124",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Research",
number = "7840",
}