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Life sciences · Journal article
Emerging Microbes & Infections · October 27, 2026
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Highly pathogenic avian influenza H5N1 2.3.4.4b genotype D1.1 lineage continues to predominate in the United States wild bird population and has spilled over into dairy cattle three independent times. To assess the transmission risk of this sublineage, we performed direct-contact transmission experiments for three distinct D1.1 strains in ferrets. Two of these strains were isolated from humans and one from a lethal cat infection. We found that only one human isolate (A/NV/10/2025) was able to transmit efficiently between ferrets. Compared to the other strains, this isolate harboured the mammalian adaptive PB2 D701N mutation, suggesting this mutation may be a candidate contributing to enhanced transmission efficiency of D1.1 as opposed to the PB2 E627 K substitution present in the lethal cat isolate. Based on these data, we conclude that the transmission fitness of D1.1 strains is modest, but special attention should be paid to emergence of adaptation at the PB2 701 position.