@article{fdi:010086598, title = {{I}nternal {RNA} 2'{O}-methylation in the {HIV}-1 genome counteracts {ISG}20 nuclease-mediated antiviral effect}, author = {{E}l {K}azzi, {P}. and {R}abah, {N}. and {C}hamontin, {C}. and {P}oulain, {L}. and {F}erron, {F} and {D}ebart, {F}. and {C}anard, {B}. and {M}iss{\'e}, {D}oroth{\'e}e and {C}outard, {B}. and {N}isole, {S}. and {D}ecroly, {E}.}, editor = {}, language = {{ENG}}, abstract = {{RNA} 2'{O}-methylation is a 'self' epitranscriptomic modification allowing discrimination between host and pathogen. {I}ndeed, human immunodeficiency virus 1 ({HIV}-1) induces 2'{O}-methylation of its genome by recruiting the cellular {FTSJ}3 methyltransferase, thereby impairing detection by {RIG}-like receptors. {H}ere, we show that {RNA} 2'{O}-methylations interfere with the antiviral activity of interferon-stimulated gene 20-k{D}a protein ({ISG}20). {B}iochemical experiments showed that {ISG}20-mediated degradation of 2'{O}-methylated {RNA} pauses two nucleotides upstream of and at the methylated residue. {S}tructure-function analysis indicated that this inhibition is due to steric clash between {ISG}20 {R}53 and {D}90 residues and the 2'{O}-methylated nucleotide. {W}e confirmed that hypomethylated {HIV}-1 genomes produced in {FTSJ}3-{KO} cells were more prone to in vitro degradation by {ISG}20 than those produced in cells expressing {FTSJ}3. {F}inally, we found that reverse-transcription of hypomethylated {HIV}-1 was impaired in {T} cells by interferon-induced {ISG}20, demonstrating the direct antagonist effect of 2'{O}-methylation on {ISG}20-mediated antiviral activity.}, keywords = {}, booktitle = {}, journal = {{N}ucleic {A}cids {R}esearch}, volume = {51}, numero = {6}, pages = {2501--2515}, ISSN = {0305-1048}, year = {2023}, DOI = {10.1093/nar/gkac996}, URL = {https://www.documentation.ird.fr/hor/fdi:010086598}, }