ISG20: an enigmatic antiviral RNase targeting multiple viruses

• Published in: FEBS open bio Vol. 12; no. 6; pp. 1096 - 1111
• Main Authors: Deymier, Séverine, Louvat, Camille, Fiorini, Francesca, Cimarelli, Andrea
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2022; Wiley Open Access/Elsevier; John Wiley and Sons Inc; Wiley
• Subjects: Amino acids; Antiviral Agents - pharmacology; antiviral proteins; Apoptosis; Chromosomes; Dengue fever; DNA; Enzymes; epitranscriptomic modifications; Estrogens; eukaryotic cells; Exoribonucleases - genetics; Genes; Hepatitis B; Infections; Interferon; Interferons - metabolism; ISG20; Kinases; Life Sciences; mechanism of action; Molecular modelling; Pathogens; Pattern recognition; Prokaryotes; prokaryotic cells; Proteins; Review; Reviews; Ribonuclease; ribonucleases; RNA; RNA polymerase; RNA, Viral - genetics; RNase; translational inhibition; virus inhibition; Virus Replication - physiology; Viruses; Viruses - genetics; Viruses - metabolism; West Nile virus; ISG20; translational inhibition; virus inhibition; epitranscriptomic modifications; interferon; RNase; ISG20, RNase, epitranscriptomic modifications, interferon, translational inhibition, virus inhibition
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.13382

Interferon‐stimulated gene 20 kDa protein (ISG20) is a relatively understudied antiviral protein capable of inhibiting a broad spectrum of viruses. ISG20 exhibits strong RNase properties, and it belongs to the large family of DEDD exonucleases, present in both prokaryotes and eukaryotes. ISG20 was initially characterized as having strong RNase activity in vitro, suggesting that its inhibitory effects are mediated via direct degradation of viral RNAs. This mechanism of action has since been further elucidated and additional antiviral activities of ISG20 highlighted, including direct degradation of deaminated viral DNA and translational inhibition of viral RNA and nonself RNAs. This review focuses on the current understanding of the main molecular mechanisms of viral inhibition by ISG20 and discusses the latest developments on the features that govern specificity or resistance to its action. ISG20 is a broad antiviral inhibitor and a potent RNase in vitro. However, a precise understanding of its mechanism of action is lacking. In this review, we discuss the latest developments on this fascinating innate defense factor.