From feather to fur: gull and mink H5N1 clade 2.3.4.4b HPAIV in their original hosts and their spillover and spillback potential

From feather to fur: spillover and spillback dynamics of H5N1 clade 2.3.4.4b at the gull–mink interface | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article From feather to fur: spillover and spillback dynamics of H5N1 clade 2.3.4.4b at the gull–mink interface Albert Perlas Puente, Ferran Tarrés-Freixas, Pierre Bessière, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7357485/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract The ongoing panzootic of H5N1 clade 2.3.4.4b high pathogenicity avian influenza virus (HPAIV) has increasingly affected non-traditional hosts like seabirds and mammals, including recent outbreaks in fur farms, in which transmission from infected gulls were suspected. To assess bird-to-mammal spillover and mammal-to-bird spillback dynamics, we performed experimental infections in yellow-legged gulls (Larus michahellis) and American minks (Neogale vison) using HPAIV strains isolated from gulls (H5N1/gull) and a farm mink outbreak (H5N1/mink). Minks challenged with H5N1/gull developed subclinical infection with limited shedding, but viral neurotropism in two out of four animals led to spontaneous emergence of key mammalian adaptation mutations in the brain, which demonstrates that H5N1 clade 2.3.4.4b spillover events from gulls to minks can lead to fast mammalian adaptation. In contrast, mammal-to-bird spillback, modelled by challenging gulls with the H5N1/mink strain, yielded no evidence of infection, suggesting a lower risk of sustained bird-mammal-bird transmission chains of 2.3.4.4b H5N1 HPAIV. Health sciences/Diseases/Infectious diseases/Influenza virus Health sciences/Diseases/Infectious diseases/Viral infection Biological sciences/Evolution/Molecular evolution Full Text Additional Declarations The authors declare no competing interests. Supplementary Files eLifesupplementaryinformation.docx Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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interface\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research 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To assess bird-to-mammal spillover and mammal-to-bird spillback dynamics, we performed experimental infections in yellow-legged gulls (Larus michahellis) and American minks (Neogale vison) using HPAIV strains isolated from gulls (H5N1/gull) and a farm mink outbreak (H5N1/mink). Minks challenged with H5N1/gull developed subclinical infection with limited shedding, but viral neurotropism in two out of four animals led to spontaneous emergence of key mammalian adaptation mutations in the brain, which demonstrates that H5N1 clade 2.3.4.4b spillover events from gulls to minks can lead to fast mammalian adaptation. In contrast, mammal-to-bird spillback, modelled by challenging gulls with the H5N1/mink strain, yielded no evidence of infection, suggesting a lower risk of sustained bird-mammal-bird transmission chains of 2.3.4.4b H5N1 HPAIV.\u003c/p\u003e","manuscriptTitle":"From feather to fur: spillover and spillback dynamics of H5N1 clade 2.3.4.4b at the gull–mink interface","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2026-01-05 22:20:42","doi":"10.21203/rs.3.rs-7357485/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2025-08-14 11:35:22","doi":"10.21203/rs.3.rs-7357485/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e4e07134-c915-4987-a001-d223eb8780d6","owner":[],"postedDate":"January 5th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":60084884,"name":"Health sciences/Diseases/Infectious diseases/Influenza virus"},{"id":60084885,"name":"Health sciences/Diseases/Infectious diseases/Viral infection"},{"id":60084886,"name":"Biological sciences/Evolution/Molecular evolution"}],"tags":[],"updatedAt":"2025-12-22T16:34:28+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-05 22:20:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-7357485","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7357485","identity":"rs-7357485","version":["v2"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}