355: Influenza D replicates in the human airway — zoonotic risk

Sanders CG et al et al., PNAS - Surveillance-derived influenza D virus (IDV) isolates were tested across cell lines, primary airway cultures, and precision-cut lung slices to assess human compatibility. IDV replicated to high titers in human respiratory models while eliciting muted interferon responses, highlighting a potential zoonotic threat and the need for enhanced surveillance. Key terms: influenza D virus, zoonosis, human airway, interferon evasion, surveillance. Study Highlights:A panel of six genetically diverse IDV isolates replicated efficiently in MDCK and A549 cell lines, primary well-differentiated human bronchial epithelial cultures, porcine airway cultures, and precision-cut lung slices. IDV induced markedly reduced IRF activation and lower IFN-λ1 and ISG expression compared to human influenza A virus, indicating limited innate immune sensing. Pretreatment with IFN-β potently restricted IDV replication, showing the virus is sensitive to an established antiviral state. Active surveillance at US swine exhibitions recovered multiple genetically distinct IDV strains spanning several clades. Conclusion:IDV readily infects and replicates in human respiratory tissues while limiting innate sensing, supporting intensified surveillance and mechanistic studies to evaluate its zoonotic and pandemic potential. Music:Enjoy the music based on this article at the end of the episode. Article title:Efficient replication of influenza D virus in the human airway underscores zoonotic potential First author:Sanders CG et al Journal:PNAS DOI:10.1073/pnas.2530325123 Reference:Sanders CG et al., Efficient replication of influenza D virus in the human airway underscores zoonotic potential. PNAS (2026) Vol. 123 No. 17 e2530325123. doi:10.1073/pnas.2530325123 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/influenza-d-human-airway-zoonotic-potential QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-05-03. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Substantively audited the transcript sections describing field surveillance, in vitro and tissue-level replication in human/porcine models, innate immune responses, receptor usage, and zoonotic implications as reported in the canonical article.- transcript topics: Field surveillance and isolation of IDV from exhibition swine; IDV replication in MDCK cells and A549 cells; Primary human and porcine airway epithelial cultures (ALI); Precision-cut lung slices (PCLS) and tissue-level replication; Innate immune sensing and interferon responses (IRF, IFN-λ1, ISGs); Interferon-β pretreatment and antiviral state QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 7- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- IDV replicates to high titers in MDCK cells and in immortalized human lung cells (A549).- IDV replicates efficiently in primary well-differentiated human airway epithelial cultures (ALI) and in porcine ALI cultures, with comparable rep... Chapters (00:00:11) - What Really Happens to Human Vibes?(00:02:04) - Disclosing the source of influenza D(00:06:08) - Human and pig lung viruses(00:12:16) - How influenza spreads like a stealthy virus(00:17:35) - Human Influenza: The Secret to Its Spread