Infectious Diseases 2025

Infectious Diseases 2025

H5N1 D1.1 shows superior adaptation to human airway compared with B3.13

25 November, 2025

A study published in The Journal of Infectious Diseases examined the pathogenicity and host-adaptation features of two avian influenza A(H5N1) genotypes, D1.1 and B3.13, in relation to human infection. The data show that genotype D1.1, which has been increasingly implicated in recent severe human cases, displays significantly higher replication efficiency in human nasal and lower-airway organoids compared with B3.13.
D1.1 binds more strongly to both α2,3- and α2,6-linked sialic acid receptors, the key determinants of tropism for avian and human respiratory epithelia, respectively. Cytokine and chemokine profiles induced by the two genotypes did not differ substantially, indicating comparable inflammatory signalling despite the marked divergence in replication dynamics. Genomic analysis identified in D1.1 several amino acid substitutions previously linked to enhanced replication in mammals, improved affinity for human-type receptors and increased potential for airborne transmissibility. These characteristics position D1.1 as a genotype with greater biological fitness in the human respiratory tract.