Pathogenicity of Highly Pathogenic Avian Influenza A/H5Nx Viruses in Avian and Murine Models

The evolution and adaptation of highly pathogenic avian influenza (HPAI) viruses pose ongoing challenges for animal and public health. We investigated the pathogenic characteristics of the newly emerged H5N1/2022 and H5N8/2022 of clade 2.3.4.4b compared to the previously circulating H5N1/2016 of clade 2.2.1.2 in Egypt using both avian and murine models. All strains demonstrated a 100% mortality in chickens after intranasal inoculation (106 EID50), while the H5N8/2022 strain showing significantly higher viral shedding (8.34 ± 0.55 log10 EID50). Contact transmission rates varied between strains (50% for the 2.3.4.4b clade and 100% for the 2.2.1.2 clade). In the mouse model, H5N1/2016 infection resulted in an 80% mortality rate with significant weight loss and virus replication in organs. In contrast, H5N8/2022 and H5N1/2022 had 60% and 40% mortality rates, respectively. An histopathological analysis revealed pronounced lesions in the tissues of the infected mice, with the most severe lesions found in the H5N1/2016 group. These findings suggest the decreased pathogenicity of the newer H5Nx strains in mammalian models, emphasizing the need for continued surveillance and adaptive control strategies.