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 replication kinetics across species.
- IDV replicates efficiently in human and swine precision-cut lung slices (PCLS).
- IDV elicits markedly weaker interferon signaling and lower IFN-λ1 and ISG induction compared with IAV.
- IDV replication is potently restricted by preactivation of antiviral state with IFN-β.
- Field surveillance at 422 swine exhibitions recovered three genetically distinct IDV strains from swine isolates (panel of six isolates used in downstream analyses).

QC result: Pass.