{"id":"doi:10.1038/s41467-026-77816-2","kind":"article","title":"Tuning intracellular immunity by Nodamura virus B2 protein enhances self-amplifying RNA activity","authors":["Sanchez-David RY","Nemegeer J","Le HD","Žusinaite E","Spiga L","Gonçalves A","Tregoning JS","Merits A","Maillard PV"],"author_count":9,"year":2026,"published":"2026-09-28","venue":"Nature communications","cited_by":0,"doi":"10.1038/s41467-026-77816-2","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41467-026-77816-2","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41467-026-77816-2","updated":null,"pmid":"42805992","pmcid":"PMC13620136","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13620136/pdf","abstract":"Self-amplifying RNA (saRNA) offers a powerful approach for vaccine development, as its replicative nature within cells provides prolonged antigen expression together with self-adjuvanticity. However, its potency is often limited by innate immune responses, particularly those triggered by intracellular double-stranded RNA (dsRNA), highlighting the need for strategies that can boost saRNA efficacy without compromising its immunostimulatory properties. Here we show that the cis-expression of the Nodamura virus (NoV) B2 protein markedly enhances saRNA-driven transgene expression by alleviating key cell-intrinsic antiviral effectors. In stem cells, NoV B2 limits the accumulation of Dicer-generated viral small RNAs, consistent with suppression of antiviral RNA interference, while in somatic cells, it prevents protein kinase R (PKR)-driven translational shutdown. NoV B2 sequesters dsRNA at the cell periphery, shielding it from antiviral effectors without suppressing type I interferon induction or signalling, thereby preserving saRNA's immunostimulatory properties, while enhancing its transgene expression potential. These findings reveal a strategy to overcome intracellular antiviral restriction of saRNA while preserving adjuvanticity, with implications for the design of more effective saRNA-based vaccines and therapeutics.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Tuning intracellular immunity by Nodamura virus B2 protein enhances self-amplifying RNA activity\" by Sanchez-David RY, Nemegeer J, Le HD et al., https://doi.org/10.1038/s41467-026-77816-2, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"mrna-cancer-vaccines","name":"mRNA Therapeutics & Cancer Vaccines","domain_slug":"medicine"}],"cited_in_dossiers":[]}