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Internal RNA 2'-O-methylation on the HIV-1 genome impairs reverse transcription.
Decombe, Alice; Peersen, Olve; Sutto-Ortiz, Priscila; Chamontin, Célia; Piorkowski, Géraldine; Canard, Bruno; Nisole, Sébastien; Decroly, Etienne.
Afiliación
  • Decombe A; Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Aix-Marseille Université, Marseille 13288, France.
  • Peersen O; Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
  • Sutto-Ortiz P; Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Aix-Marseille Université, Marseille 13288, France.
  • Chamontin C; Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique, Université de Montpellier, Montpellier 34090, France.
  • Piorkowski G; Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207), 13005 Marseille, France.
  • Canard B; Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Aix-Marseille Université, Marseille 13288, France.
  • Nisole S; Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique, Université de Montpellier, Montpellier 34090, France.
  • Decroly E; Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique, Aix-Marseille Université, Marseille 13288, France.
Nucleic Acids Res ; 52(3): 1359-1373, 2024 Feb 09.
Article en En | MEDLINE | ID: mdl-38015463
Viral RNA genomes are modified by epitranscriptomic marks, including 2'-O-methylation that is added by cellular or viral methyltransferases. 2'-O-Methylation modulates RNA structure, function and discrimination between self- and non-self-RNA by innate immune sensors such as RIG-I-like receptors. This is illustrated by human immunodeficiency virus type-1 (HIV-1) that decorates its RNA genome through hijacking the cellular FTSJ3 2'-O-methyltransferase, thereby limiting immune sensing and interferon production. However, the impact of such an RNA modification during viral genome replication is poorly understood. Here we show by performing endogenous reverse transcription on methylated or hypomethylated HIV-1 particles, that 2'-O-methylation negatively affects HIV-1 reverse transcriptase activity. Biochemical assays confirm that RNA 2'-O-methylation impedes reverse transcriptase activity, especially at low dNTP concentrations reflecting those in quiescent cells, by reducing nucleotide incorporation efficiency and impairing translocation. Mutagenesis highlights K70 as a critical amino acid for the reverse transcriptase to bypass 2'-O-methylation. Hence, the observed antiviral effect due to viral RNA 2'-O-methylation antagonizes the FTSJ3-mediated proviral effects, suggesting the fine-tuning of RNA methylation during viral replication.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Replicación Viral / ARN Viral / Procesamiento Postranscripcional del ARN / VIH-1 / Transcriptasa Inversa del VIH Límite: Humans Idioma: En Revista: Nucleic Acids Res Año: 2024 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Replicación Viral / ARN Viral / Procesamiento Postranscripcional del ARN / VIH-1 / Transcriptasa Inversa del VIH Límite: Humans Idioma: En Revista: Nucleic Acids Res Año: 2024 Tipo del documento: Article País de afiliación: Francia