30 August 2026
Johns Hopkins researchers found that while emerging H5N1 clade 2.3.4.4b genotypes replicate robustly at core human and bovine body temperatures, cooler nasal temperatures significantly suppress viral growth, revealing a key physiological barrier against efficient human-to-human transmission.
Using differentiated primary human nasal (hNEC) and bronchial (hBEC) epithelial cell cultures at an air-liquid interface, researchers compared two B3.13 (bovine-origin) isolates and one D1.1 (poultry-origin) isolate against seasonal H1N1pdm09 across three physiological temperatures (33°C, 37°C, and 39°C).
- Unlike seasonal H1N1, which replicated efficiently at 33°C, all H5N1 isolates showed delayed growth and lower viral output at human upper respiratory tract temperature (33°C).
- At 37°C (core human) and 39°C (bovine udder/avian core), the B3.13 genotype reached high viral titers comparable to seasonal H1N1(~109-1010TCID50/mL). In contrast, the D1.1 genotype remained significantly attenuated across all conditions.
- All H5N1 isolates preferentially infected ciliated cells in both nasal and bronchial tissues. Mucosal innate immune responses were driven primarily by tissue origin and temperature rather than viral subtype, showing suppressed early interferon and chemokine responses at 33°C.
The data indicate that while current H5N1 B3.13 isolates are replication-competent in deep mammalian tissues, upper airway temperature (33°C) serves as an active barrier against human nasal colonization. Surveillance in poultry and cattle must monitor for adaptive mutations in the polymerase complex (e.g., PB2) that could enhance viral replication kinetics in cooler human airways.
Werner, A. P., Sachithanandham, J., Akin, E., Talukdar, S. N., Pinsley, M., & Pekosz, A. (2026). Influenza A virus H5N1 genotypes B3.13 and D1.1 show temperature-dependent restriction of replication in primary human respiratory epithelial cell cultures derived from the upper and lower respiratory tract. bioRxiv, 2026.08.27.747488.
