Internal RNA 2′O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nucleic Acids Research Année : 2022

Internal RNA 2′O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect

Résumé

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.
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Dates et versions

hal-03860650 , version 1 (20-11-2022)

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Paternité - Pas d'utilisation commerciale

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Priscila El Kazzi, Nadia Rabah, Célia Chamontin, Lina Poulain, François Ferron, et al.. Internal RNA 2′O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect. Nucleic Acids Research, 2022, ⟨10.1093/nar/gkac996⟩. ⟨hal-03860650⟩
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