El Kazzi P. auteur aut IRD Rabah N. auteur aut IRD Chamontin C. auteur aut IRD Poulain L. auteur aut IRD Ferron F auteur aut IRD Debart F. auteur aut IRD Canard B. auteur aut IRD Missé Dorothée auteur aut IRD Coutard B. auteur aut IRD Nisole S. auteur aut IRD Decroly E. auteur aut IRD text journalArticle eng text/pdf reformatted digital access RNA 2'O-methylation is a 'self' epitranscriptomic modification allowing discrimination between host and pathogen. Indeed, human immunodeficiency virus 1 (HIV-1) induces 2'O-methylation of its genome by recruiting the cellular FTSJ3 methyltransferase, thereby impairing detection by RIG-like receptors. Here, we show that RNA 2'O-methylations interfere with the antiviral activity of interferon-stimulated gene 20-kDa protein (ISG20). Biochemical experiments showed that ISG20-mediated degradation of 2'O-methylated RNA pauses two nucleotides upstream of and at the methylated residue. Structure-function analysis indicated that this inhibition is due to steric clash between ISG20 R53 and D90 residues and the 2'O-methylated nucleotide. We confirmed that hypomethylated HIV-1 genomes produced in FTSJ3-KO cells were more prone to in vitro degradation by ISG20 than those produced in cells expressing FTSJ3. Finally, we found that reverse-transcription of hypomethylated HIV-1 was impaired in T cells by interferon-induced ISG20, demonstrating the direct antagonist effect of 2'O-methylation on ISG20-mediated antiviral activity. specialized 020 052 51 6 2501-2515 2023 0305-1048 https://www.documentation.ird.fr/hor/fdi:010086598 10.1093/nar/gkac996 0305-1048 [F B010086598] https://www.documentation.ird.fr/hor/fdi:010086598 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2023-06/010086598.pdf IRD - Base Horizon / Pleins textes 2022-12-02 2026-06-12 fdi:010086598 fre