{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:08:32Z","timestamp":1793214512435,"version":"4.5.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Viruses, particularly Epstein\u2013Barr virus (EBV), are strongly implicated in multiple sclerosis (MS) pathogenesis, yet reliable biomarkers of active viral replication remain limited. Double-stranded RNA (dsRNA) represents a hallmark of viral replication and may serve as a measurable indicator of viral infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a sandwich ELISA to quantify dsRNA levels in matched plasma and cerebrospinal fluid (CSF) samples from 70 treatment-na\u00efve MS patients at first clinical onset and in plasma from 26 sex- and age-matched healthy controls. We additionally assessed plasma and CSF antiviral cytokine concentrations and designed an indirect ELISA to measure anti-dsRNA antibody levels using poly(I:C) as the target antigen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Plasma dsRNA levels were significantly elevated in MS patients compared to controls and positively correlated with antiviral cytokines, including GM-CSF, IFN-\u03bb1, IFN-\u03bb2\/3, IFN-\u03b3, IFN-\u03b12, and IL-12p70. CSF samples exhibited increased IP-10 and IL-8 levels, and the single patient with detectable CSF dsRNA showed among the highest concentrations of both cytokines. A subset of ten patients (14%) with serological evidence of atypical EBV reactivation (EBNA1 IgG\n                      <jats:sup>+<\/jats:sup>\n                      \/IgM\n                      <jats:sup>+<\/jats:sup>\n                      ) had higher plasma dsRNA and antiviral cytokine levels than the remaining patients. Anti-dsRNA IgM, but not IgG or IgA, correlated positively with plasma dsRNA in both MS patients and controls, yet anti-dsRNA IgM levels were significantly reduced in MS compared to controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings identify increased plasma viral dsRNA coupled with reduced anti-dsRNA IgM antibody levels as potential biomarkers for a subpopulation of early MS patients and indicate a dysregulated anti-viral immune response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1706133","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T06:29:12Z","timestamp":1764311352000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Double-stranded RNA antiviral signature in early multiple sclerosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Vasileios","family":"Gouzouasis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Sarrigeorgiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaritis","family":"Tsifintaris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikos","family":"Markoglou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urania","family":"Georgopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Lymberi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Anagnostouli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Probert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Giannakakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1136\/jnnp-2020-322941","article-title":"Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis","volume":"91","author":"Abrahamyan","year":"2020","journal-title":"J. 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