Investigation of the pathogenic potential and the possibility of cross-species transmission of H5 avian influenza viruses detected on the territory of the Russian Federation in 2018–2022

Introduction. The rapid evolution of highly pathogenic avian influenza (HPAI) viruses through antigenic drift and reassortment can lead to enhanced replication efficiency and cross-species transmission to mammals, as evidenced by recent outbreaks in various animal populations. Identifying mammalian pathogenicity markers in circulating HPAI viruses is crucial for evaluating their pathogenic potential and ability to cross species barriers. The aim. This study analyzed genomic sequences of highly pathogenic H5 avian influenza virus (AIV) isolates collected in the Russian Federation between 2018 and 2022. Materials and methods. We utilized original complete genome sequencing data alongside with nucleotide sequences of H5 AIV isolates and strains available in public databases. Results. Analysis revealed a predominance of viruses with replication complexes adapted to avian cells. Examination of viral hemagglutinin amino acid sequences showed that most strains maintained receptor-binding sites of avian origin, with enhanced affinity for SAα-2,3-Gal receptors present in avian epithelial cells. However, we identified several mammalian virulence factors that have emerged and spread within the avian influenza virus population, including full-length active PB1-F2 protein, a 5-amino-acid insertion in the NS1 protein, and specific amino acid substitutions in the M1 protein. Conclusion. The presence of mammalian pathogenicity factors in the avian influenza virus population may facilitate successful cross-species transmission through suppression of specific immune responses, followed by adaptation of viral hemagglutinin to mammalian cell receptors through antigenic drift and natural selection. The observed elimination of certain adaptive mutations from the avian influenza virus population validates the effectiveness of stamping-out policies and vaccination restrictions in industrial poultry farming as important measures to mitigate the zoonotic potential of avian influenza.