Expanding Host Range of Avian Influenza Virus: H5N1 Subtype

The avian influenza viruses (AIV) belong to Orthomyxoviridae family and are classified as influenza A viruses. AIV has eight segments of single-stranded RNAs with a negative polarity that encode 11 proteins. Two groups of the most important subtypes of AIV are H5 and H7, which infect humans, and some of them are highly pathogenic. H5N1 and H7N9 were reported for the first time in Hong Kong in 1997 and China in 2013, and so far, have demonstrated 52% (H5N1) and 40% (H7N9) case-fatality in humans. Unlike H7N9, which has a narrow host range, including birds and humans, H5N1 has a broad host range, including birds, various mammals, and humans. This broad host range, along with mammalian adapting mutations (especially PB2-E627K), raises concerns= about its potential to adapt to humans and cause pandemics. Evidence of mammal-to-mammal transmission, foodborne transmission, and the systemic infection of H5N1 in mammals has been observed in European and Canadian foxes, as well as marine mammals in South American countries. The main concern about AIVs in 2024 is the infection of dairy cattle in the US by H5N1. This outbreak occurred in cows, which are considered resistant to influenza A viruses. Some significant observations in this outbreak are transmission of H5N1 between cows, release of H5N1 into cows’ milk and as a result milk contamination with H5N1 and transmission to humans. In conclusion, based on the patterns of mammalian infection in the past decade, particularly in the last four years in the Americas, we can anticipate further adaptations of H5N1 in different mammalian species and ultimately human hosts, leading to systemic infections and new pathways for transmission.