Cross-Species Transmission of Highly Pathogenic Avian Influenza (HPAI) H5N1 Virus in the U.S. Dairy Cattle: A Comprehensive Review

There are four types of influenza viruses: A, B, C, and D. Cattle are susceptible to influenza D infection and serve as a reservoir for this seven-segmented influenza virus. It is generally thought that bovines are not a host of other types of influenza viruses including type A. This long-standing viewpoint has been challenged by the recent highly pathogenic avian influenza (HPAI) H5N1 outbreaks in dairy cows in the United States. To date, HPAI H5N1 has spread into nine states affecting 49 dairy herds and causing clinical symptoms including reduced appetite, fever, and a sudden drop in milk production. This review article describes the current epidemiological landscape of HPAI H5N1 in U.S. dairy cows and the recent interspecies transmission events of HPAI H5N1 in other mammals reported in other countries. The review also discusses adaptation mutations of HPAI H5N1 to mammalian hosts and vaccination strategies. Finally, it summarizes some immediate questions that need to be addressed towards a better understanding of infection biology, transmission, and immune response of HPAI H5N1 in bovines.