Clade 2.3.4.4b H5N1 Influenza A Virus Exhibits High Infectivity in Human Respiratory Tract Models

To investigate the pathogenicity and host response of the newly emerged A/Cattle/Texas/063224-24-1/2024 (H5N1b/2024) strain in comparison to reference viruses, we performed bulk RNA sequencing of primary human respiratory models, including ex vivo alveolar lung tissue (aHuLu), organoid-derived bronchial epithelium (brEp), and 3D nasal air-liquid interface epithelium (nALI).

Infections were carried out in parallel with H5N1/2004 (clade 1), H3N2/1999 (seasonal influenza A), and H5N8/2016 (low pathogenic avian influenza). Differential gene expression analysis was performed with DESeq2, including donor as a covariate. The dataset provides genome-wide transcriptional profiles at 24 h post-infection, enabling comparative analysis of viral replication, host immune activation, and tissue-specific responses across human respiratory compartments.