Unique immune and other responses of human nasal epithelial cells infected with H5N1 avian influenza virus compared to seasonal human influenza A and B viruses.

Summary

Using primary human nasal epithelial ALI cultures, H5N1 induced a signature of blunted antiviral and inflammasome responses, impaired wound repair and barrier integrity, and altered ion/solute transport gene expression compared to seasonal influenza. These distinct host responses suggest biomarkers and therapeutic targets for surveillance and early intervention against HPAI.

Key Findings

• H5N1 elicited reduced IFN-β and inflammasome mediator (IL-1α/IL-1β) expression in human nasal epithelium versus seasonal strains.
• H5N1 impaired wound healing, re-epithelialization, and barrier integrity; oxidative stress responses were diminished.
• H5N1 increased expression of transmembrane solute and ion carrier genes, indicating altered epithelial transport states.

Clinical Implications

Supports development of upper-airway diagnostics and therapies that restore type I IFN signaling and epithelial repair to contain HPAI spread and severity.

Limitations

• In vitro model without in vivo validation of clinical correlates
• H5N1 adaptation differences in the nasal compartment may limit generalizability

Future Directions

Validate signatures in vivo and in clinical upper-airway samples; test interventions enhancing IFN responses and epithelial repair; evaluate donor variability and age/host factors.