Abstract
The numerous global outbreaks and continuous reassortments of highly pathogenic avian influenza (HPAI) A(H5N6/H5N8) clade 2.3.4.4 viruses in birds pose a major risk to the public health. We investigated the tropism and innate host responses of 5 recent HPAI A(H5N6/H5N8) avian isolates of clades 2.3.4.4b, e, and h in human airway organoids and primary human alveolar epithelial cells. The HPAI A(H5N6/H5N8) avian isolates replicated productively but with lower competence than the influenza A(H1N1)pdm09, HPAI A(H5N1), and HPAI A(H5N6) isolates from humans in both or either models. They showed differential cellular tropism in human airway organoids; some infected all 4 major epithelial cell types: ciliated cells, club cells, goblet cells, and basal cells. Our results suggest zoonotic potential but low transmissibility of the HPAI A(H5N6/H5N8) avian isolates among humans. These viruses induced low levels of proinflammatory cytokines/chemokines, which are unlikely to contribute to the pathogenesis of severe disease.
Highlights
The numerous global outbreaks and continuous reassortments of highly pathogenic avian influenza (HPAI) A(H5N6/H5N8) clade 2.3.4.4 viruses in birds pose a major risk to the public health
A, B) Replication in human airway organoids infected with 6 log TCID50/mL virus (A) and primary human alveolar epithelial cells infected at multiplicity of infection 0.01 at 37°C (B)
Statistical significance between AUC values was analyzed by using 1-way analysis of variance with Bonferroni posttests. *p
Summary
The numerous global outbreaks and continuous reassortments of highly pathogenic avian influenza (HPAI) A(H5N6/H5N8) clade 2.3.4.4 viruses in birds pose a major risk to the public health. The HPAI A(H5N6/H5N8) avian isolates replicated productively but with lower competence than the influenza A(H1N1)pdm, HPAI A(H5N1), and HPAI A(H5N6) isolates from humans in both or either models They showed differential cellular tropism in human airway organoids; some infected all 4 major epithelial cell types: ciliated cells, club cells, goblet cells, and basal cells. Since early 2014, novel reassortant HPAI A(H5N6/H5N8) viruses of clade 2.3.4.4 have gained attention because of their rapid evolution and global spread. They have been widely distributed among regions of Asia, Europe, and Africa and have been reported in North America (mainly in the United States and Canada), accompanied. An HPAI H5N8 clade 2.3.4.4 virus quickly acquired virulence markers, enhancing its virulence in mice and replication and polymerase activity in human cell lines within 5 murine passages [14], suggesting potential rapid adaptation after repeated virus introduction
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