Emerging Threats of Highly Pathogenic Avian Influenza A (H5N1) in US Dairy Cattle: Understanding Cross-Species Transmission Dynamics in Mammalian Hosts

Abstract

The rapid geographic spread of the highly pathogenic avian influenza (HPAI) A(H5N1) virus in poultry, wild birds, and other mammalian hosts, including humans, raises significant health concerns globally. The recent emergence of HPAI A(H5N1) in agricultural animals such as cattle and goats indicates the ability of the virus to breach unconventional host interfaces, further expanding the host range. Among the four influenza types-A, B, C, and D, cattle are most susceptible to influenza D infection and serve as a reservoir for this seven-segmented influenza virus. It is generally thought that bovines are not hosts for other types of influenza viruses, including type A. However, this long-standing viewpoint has been challenged by the recent outbreaks of HPAI A(H5N1) in dairy cows in the United States. To date, HPAI A(H5N1) has spread into fourteen states, affecting 299 dairy herds and causing clinical symptoms such as reduced appetite, fever, and a sudden drop in milk production. Infected cows can also transmit the disease through raw milk. This review article describes the current epidemiological landscape of HPAI A(H5N1) in US dairy cows and its interspecies transmission events in other mammalian hosts reported across the globe. The review also discusses the viral determinants of tropism, host range, adaptative mutations of HPAI A(H5N1) in various mammalian hosts with natural and experimental infections, and vaccination strategies. Finally, it summarizes some immediate questions that need to be addressed for a better understanding of the infection biology, transmission, and immune response of HPAI A(H5N1) in bovines.

Keywords: H5N1; cattle; high pathogenic avian influenza (HPAI); transmission.

Figure 1

Current status of HPAI A(H5N1) virus spread in the US dairy cow herds. As of 14 October 2024, HPAI A(H5N1) virus was detected in 299 dairy cow herds in fourteen states of the US. The number of herds affected in each state was color-coded and shown. Data were obtained from USDA website (https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/livestock, accessed on 15 August 2024). Map image was downloaded from https://inkpx.com, accessed on 15 August 2024.

Figure 2

Cross-species transmission and host range of HPAI A(H5N1). Wild aquatic birds are the reservoir hosts for type A avian influenza viruses. Wild birds, wild mammals, poultry, and domestic/pet animals were affected by HPAI A(H5N1). The bold dark blue arrows denote frequent spillover events, while the gray arrows denote sporadic/infrequent spillover. Sustained human-to-human transmission has not been reported. Vector images were downloaded from Freepik (www.freepik.com, accessed on 15 August 2024), vecteezy (https://www.vecteezy.com/, accessed on 15 October 2024), and Microsoft Office icons.