Horizon 1 1 17 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES Nucleic Acids Research 2501-2515 2023 fdi:010086598 ENG Nucleic Acids Research 0305-1048 ISI:000880639500001 6 10.1093/nar/gkac996 https://www.documentation.ird.fr/hor/fdi:010086598 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2023-06/010086598.pdf 51 Horizon (IRD) 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. 020 ; 052 UR224 / UR190