H9N2 AI strain has potential to spark human pandemic
Avian influenza A (H9N2) viruses have been circulating in poultry for decades and occasionally infect humans, typically causing mild disease. However, recent reports indicate an increasing number of human cases, suggesting enhanced viral adaptation to mammalian hosts. H9N2 viruses are of particular concern because they not only infect humans but also donate internal genes to other avian influenza viruses, including H5N1, H7N9, and H10N8, which have caused severe human disease. To assess whether contemporary H9N2 viruses have acquired greater human adaptation, a new study compared a 2024 human H9N2 isolate with a historical human isolate from 1999.
The 2024 H9N2 isolate replicated more efficiently than the 1999 strain in both MDCK cells and human respiratory organoids, whereas the older strain failed to replicate in organoids. The contemporary virus exhibited a higher infection rate in both ciliated and non-ciliated cells and demonstrated stronger affinity for α2,6-linked sialic acid receptors typical of human airways. Genomic analysis revealed multiple mammalian-adaptive amino acid substitutions in the hemagglutinin and polymerase complex genes. Comparative sequence analysis of over 14,000 avian and 96 human H9N2 strains from GISAID confirmed that such mammalian-adaptation markers have become increasingly prevalent in recent human isolates.
The researchers concluded that the contemporary 2024 H9N2 virus exhibits substantially greater replication efficiency in human upper and lower respiratory organoids than the historical 1999 strain, reflecting improved adaptation to human hosts.
