{
  "abstract": "An apparent paradox drives this study: H3N2 influenza virus concentrates in the brain of infected 10-day chicken embryos while kidney and lung, which express the same viral entry receptors (ST3GAL3 and other sialic acid receptors), are essentially virus-free. Using mRNA-seq on brain, kidney, and lung from H3N2-infected 10-day chicken embryos, we establish and propose a resolution to this paradox, by identifying immune privilege, rather than neurotropism, as the more likely explanation; circulating macrophages likely clear the virus from peripheral tissues but seemingly cannot cross the embryonic brain barrier. The innate response is robust despite lacking RIG-I:MDA5/IFIH1 and TLR3-TLR7-IRF signaling compensate robustly, likely driving complete viral clearance in peripheral organs. At 48 h post-infection, macrophages in kidney and lung are in a post-clearance M2 state; complement is activated but lacks both the H3N2-specific anti-bodies and the terminal C9 component for productive effect. These findings challenge the hypothesis that RIG-I loss necessarily renders chickens more susceptible to influenza: complete peripheral clearance of a productively infecting H3N2 strain in the absence of RIG-I is difficult to reconcile with an obligate role for RIG-I in this host's antiviral defense. We also identify the embryonic brain as a potentially immune-privileged viral sanctuary with implications for influenza neurological disease in young hosts.",
  "abstract_shown": true,
  "affiliations": [
    "New York Medical College"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "O. S. Gurses Sahin"
    },
    {
      "name": "J. B. Fung"
    },
    {
      "name": "D. Lehri"
    },
    {
      "affs": [
        0
      ],
      "name": "R. Sachidanandam"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5q2dv2bbwekhm.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.05.11.723864",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.05.11.723864v2.full",
  "id": "5q2dv2bbwekhm",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.05.11.723864v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2713|Influenza Virus Research Studies"
    ]
  ],
  "openalex": "W7161122008",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.05.11.723864v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-05-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5q2dv2bbwekhm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:07Z",
      "native_id": "10.64898/2026.05.11.723864",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.05.11.723864v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Embryonated chicken eggs clear systemic H3N2 influenza without RIG-I: transcriptomic evidence for innate sufficiency and brain immune privilege",
  "title_text": "Embryonated chicken eggs clear systemic H3N2 influenza without RIG-I: transcriptomic evidence for innate sufficiency and brain immune privilege",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:07Z",
  "url": "https://research.draconitic.com/paper/5q2dv2bbwekhm",
  "venue": "bioRxiv",
  "versions": []
}