El Kazzi P., Rabah N., Chamontin C., Poulain L., Ferron F, Debart F., Canard B., Missé Dorothée, Coutard B., Nisole S., Decroly E. (2023). Internal RNA 2'O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect. Nucleic Acids Research, 51 (6), 2501-2515. ISSN 0305-1048.
Titre du document
Internal RNA 2'O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect
Année de publication
El Kazzi P., Rabah N., Chamontin C., Poulain L., Ferron F, Debart F., Canard B., Missé Dorothée, Coutard B., Nisole S., Decroly E.
Nucleic Acids Research, 2023,
51 (6), 2501-2515 ISSN 0305-1048
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.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche 
Entomologie médicale / Parasitologie / Virologie 
Fonds IRD [F B010086598]