Abstract Avian influenza H5N1 clade 2.3.4.4b viruses caused a global panzootic and, unexpectedly, widespread outbreaks in dairy cattle , therefore representing a pandemic threat . To inform control strategies, it is critical to determine whether the potential to adapt to bovine cells is a general feature of H5N1 viruses , is specific to viruses of clade 2.3.4.4b, or narrowly restricted to some genotypes within this clade. Using a large panel of recombinant viruses representing >60 years of H5N1 history and other IAVs for comparison, we demonstrate replicative fitness in bovine cells is: (i) highly variable across 2.3.4.4b genotypes, (ii) limited in viruses predating the global expansion of this clade , (iii) determined by the internal gene cassette, and (iv) not restricted to udder epithelial cells. Mutations in the PB2 polymerase subunit emerge as key determinants of adaptation , although their phenotypic effects are context dependent. Bovine B3.13 and some avian genotypes ex...
Media Monitoring for Signals about Emerging Threats