Published on 23 September 2026

A bovine H5N1 virus efficiently replicates in differentiated human nasal epithelial cells

The continued spread of H5N1 influenza viruses in dairy cattle has raised questions about their zoonotic potential. In a new study, researchers at the IVI investigated how a bovine H5N1 virus interacts with differentiated human nasal epithelial cells.

Significance of the study

The continuing spread of H5N1 influenza viruses in dairy cattle has significantly increased the risk of human exposure. However, infections in humans have mostly only resulted in mild symptoms, and no human-to-human transmission has been observed to date. This study provides experimental evidence that a bovine H5N1 virus that was isolated during the dairy cow outbreak in Texas in 2024 can efficiently replicate in human nasal epithelial cells that have been differentiated at the air-liquid interface. This finding suggests that the virus already possesses the properties needed to promote replication in these human epithelial cells. Our data therefore help understand the zoonotic potential of H5N1 viruses originating in cattle, but they don’t explain why there has been no in vivo human-to-human transmission to date.

• Study overview

  This study examined whether an H5N1 virus originating in dairy cows can infect and replicate in human upper airway cells. Using a physiologically relevant model of differentiated human nasal epithelial cells, staff at the IVI studied the virus replication at different temperatures, cell tropism, receptor use and the host’s innate immune response. Our findings suggest that human upper airways are highly susceptible to infection with the bovine H5N1 viruses that are currently circulating.

• Key findings

  • An H5N1 virus originating in dairy cows replicates in differentiated human nasal epithelial cells just as efficiently as a pandemic H1N1 virus from 2009, both at 37°C and at 33°C.
  • Differentiated nasal epithelial cells express receptors for both human and avian flu viruses, thereby making a change in receptor specificity unnecessary.
  • The replication of the H5N1 virus from dairy cows at 33 °C largely depended on the adaptive mutations PB1 M631L and PA K497R.
  • An avian H5N1 virus of clade 2.3.4.4b also replicates efficiently in human nasal epithelial cells, but is attenuated at 33°C.
  • The bovine H5N1 virus blocks the production of interferon-λ, but remains sensitive to the antiviral effects of this cytokine.

• Future directions

  Our results underscore the importance of ongoing surveillance of H5N1 viruses and continued research into improving pandemic preparedness.
  The authors’ results point to several important areas for future research:

  • Determining which genetic changes in the virus would be needed to allow efficient human-to-human transmission.
  • Evaluating the behaviour of bovine H5N1 viruses in other human airway models and animal transmission models.
  • Studying how the viral evolution during circulation in mammals could influence the infectivity, immune evasion and transmissibility.
  • Assessing the efficacy of existing antiviral medicines and vaccines against emerging bovine H5N1 variants.
  • Continuing the integrated monitoring at the intersection between animals and humans to identify viral adaptations that could increase the pandemic risk.

Title and link

A bovine H5N1 virus efficiently replicates in differentiated human nasal epithelial cells
NPJ Viruses (2026)

Authors

Étori Aguiar Moreira, Samuel Constant, Charlène Constant, Lisa Butticaz, Michele Wyler, Teodora David, Peter M. Grin, Charaf Benarafa, Volker Thiel, Marco P. Alves & Gert Zimmer