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Peer-reviewedCC BY-NC-ND 4.0Cell Reports

An Epstein-Barr virus-encoded snoRNA directs 2′-O-methylation of human rRNAs to control translation and the viral lytic switch

Abstract

Epstein-Barr virus (EBV) establishes life-long latency in human B cells yet the molecular strategies that balance its persistence with lytic replication remain incompletely understood. Here, we identify the EBV-encoded small nucleolar RNA, v-snoRNA1, as a bona fide 2′-O-methylation guide that directs methylation of host ribosomal RNAs at 18S-C621 and 28S-U1760, two conserved residues in the ribosomal A-site. V-snoRNA1-mediated hypermethylation impairs 18S rRNA maturation and compromises translational fidelity and output, resulting in slower cellular proliferation. Infection with a v-snoRNA1 deleted virus (Δv-snoRNA1) leads to enhanced protein synthesis and increased proliferation, together with extensive rewiring of host and viral gene expression. This rewiring includes suppression of immune and interferon pathways and alterations in transcription factor activities important for B cell differentiation. Importantly, we find that v-snoRNA1 is required to facilitate viral production. Our findings reveal a molecular strategy by which EBV directly controls translation to promote infection.

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BibTeX
@article{dan2026epsteinbarr,
  title = {{An Epstein-Barr virus-encoded snoRNA directs 2′-O-methylation of human rRNAs to control translation and the viral lytic switch}},
  author = {Yarden Dan and Beáta E Jády and Yudit Halperin and Yuval Nevo and Aliza Fedorenko and Anat Bashan and Maram Arafat and Pnina Glick and Ada Yonath and Tamás Kiss and Daphna Nachmani},
  journal = {Cell Reports},
  year = {2026},
  month = nov,
  doi = {10.1016/j.celrep.2026.117814},
  url = {https://hal.science/hal-05848078v1},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - An Epstein-Barr virus-encoded snoRNA directs 2′-O-methylation of human rRNAs to control translation and the viral lytic switch
AU  - Yarden Dan
AU  - Beáta E Jády
AU  - Yudit Halperin
AU  - Yuval Nevo
AU  - Aliza Fedorenko
AU  - Anat Bashan
AU  - Maram Arafat
AU  - Pnina Glick
AU  - Ada Yonath
AU  - Tamás Kiss
AU  - Daphna Nachmani
PY  - 2026
DA  - 2026/11/02
JO  - Cell Reports
DO  - 10.1016/j.celrep.2026.117814
UR  - https://hal.science/hal-05848078v1
AB  - Epstein-Barr virus (EBV) establishes life-long latency in human B cells yet the molecular strategies that balance its persistence with lytic replication remain incompletely understood. Here, we identify the EBV-encoded small nucleolar RNA, v-snoRNA1, as a bona fide 2′-O-methylation guide that directs methylation of host ribosomal RNAs at 18S-C621 and 28S-U1760, two conserved residues in the ribosomal A-site. V-snoRNA1-mediated hypermethylation impairs 18S rRNA maturation and compromises translational fidelity and output, resulting in slower cellular proliferation. Infection with a v-snoRNA1 deleted virus (Δv-snoRNA1) leads to enhanced protein synthesis and increased proliferation, together with extensive rewiring of host and viral gene expression. This rewiring includes suppression of immune and interferon pathways and alterations in transcription factor activities important for B cell differentiation. Importantly, we find that v-snoRNA1 is required to facilitate viral production. Our findings reveal a molecular strategy by which EBV directly controls translation to promote infection.
SN  - 2211-1247
SN  - 2211-1247
ER  -