Lancet Microbe | 2025
20 December 2025
A new study published in The Lancet Microbe reveals that contemporary clade 2.3.4.4b H5N1 influenza viruses, including those recently isolated from cows and wildlife, exhibit phenotypic changes that may increase their risk for human infection compared to older H5N1 strains. Researchers from the Erasmus University Medical Center investigated the attachment and replication efficiency of three recent H5N1 clade 2.3.4.4b viruses (Gull2022, Polecat2022, and Bovine2024) and compared them to a 2005 H5N1 strain.
All tested clade 2.3.4.4b viruses attached significantly more efficiently to cells in both the human upper and lower respiratory tracts compared to the older H5N1 strain from 2005. These contemporary viruses successfully replicated in human nasal and tracheobronchial respiratory epithelium cultures. Notably, the H5N1 Gull2022 virus replicated as efficiently as seasonal H3N2 in tracheobronchial cultures. Clade 2.3.4.4b viruses differ from the 2005 strain by five amino acids located near the haemagglutinin receptor binding site, which likely contributes to the observed increase in attachment. Infection with recent H5N1 viruses triggered a broader antiviral innate immune response in respiratory cultures than the 2005 virus. The study suggests that the increased ability of circulating clade 2.3.4.4b viruses to target the human respiratory tract likely contributes to an elevated risk of human infection and provides more opportunities for the virus to adapt to human hosts.
