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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\n                    <jats:italic>cis<\/jats:italic>\n                    -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\u2019s 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.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-77816-2","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T09:03:08Z","timestamp":1790586188000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tuning intracellular immunity by Nodamura virus B2 protein enhances self-amplifying RNA activity"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7110-0189","authenticated-orcid":false,"given":"Raul Y.","family":"Sanchez-David","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-8924","authenticated-orcid":false,"given":"Josephine","family":"Nemegeer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9350-2840","authenticated-orcid":false,"given":"Hoang Duy","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"\u017dusinaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Spiga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8093-8741","authenticated-orcid":false,"given":"John S.","family":"Tregoning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8193-0071","authenticated-orcid":false,"given":"Andres","family":"Merits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4611-388X","authenticated-orcid":false,"given":"Pierre V.","family":"Maillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"77816_CR1","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.ymthe.2017.11.017","volume":"26","author":"AB Vogel","year":"2018","unstructured":"Vogel, A. 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