Abstract
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 (10(6) 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.