Mutations affecting pathogenicity and host range of H5N1 clade 2.3.4.4b represent the potential for emergence of a zoonotic strain.  Studies conducted in South Korea in collaboration with virologists at St. Jude Children’s Hospital have demonstrated cell-mediated systemic dissemination, neural involvement and mortality in a ferret model.

The strain GA/W22-145E/22 derived from a scaup was subjected to molecular evaluation.  The studies demonstrated mutations PB24718 and NP450N.  These changes were responsible for enhanced polymerase activity and replication in both human peripheral blood mononuclear cells and in bovine mammary gland tissue.  The markers that were identified by single cell rNA sequencing in combination with reverse genetics demonstrated that mutations in the PB2 and NP genes can vastly alter pathogenicity.

It is presumed that mutations arose from reassortment of Eurasian 2.3.4.4b H5N1 viruses with North American low-pathogenicity strains to incorporate gene segments into virus circulating among wild birds with spillover to commercial flocks and dairy herds.

Emergence of enhanced virulence with neurotropism suggest enhanced measures to control and prevent avian influenza in commercial poultry flocks.  The greater the number of birds infected especially on large egg-production complexes and in areas with a high density of turkeys will contribute to the emergence of mutant viruses with increased pathogenicity.

Extensive outbreaks of H5N1 B3-13 strain in dairy herds coupled with devastating mortality among marine mammals should serve as a warning to public health regulators of the risk of H5N1 zoonosis.  The implications of a human outbreak with the costs and disruption as experienced during the COVID pandemic should be considered in relation to current policy relating to control that excludes vaccination of commercial flocks at risk.  Preservation of the current export market for broiler leg quarters is a valid consideration, but the risks and consequences of a human pandemic should be considered in developing a strategy for deployment of vaccines.

In the unfortunate event of extension of H5N1 to human populations, those opposing vaccination based on retention of exports applying spurious scientific interpretations will have to answer to a higher authority.

*Young-Il Kim et al., North American H5N1 viruses with mutations infect immune cells. Science Advances doi:10.1126/sciadv.adv1208 September 2025.