A 2024 outbreak of highly pathogenic avian influenza (HPAI) H5N1 virus in U.S. dairy cattle has raised concerns about its potential to infect and transmit among mammals. The virus, isolated from infected cow milk, was found to replicate systemically in mice and ferrets, including in mammary glands. It binds to both α2,3 and α2,6 sialic acid residues, enabling it to infect human-like respiratory tissues. However, transmission to ferrets via respiratory droplets was inefficient, with only one of four exposed ferrets showing seroconversion without detectable virus in nasal swabs. The virus can be transmitted from lactating mice to their pups through milk, but not to adult contact animals. The study also found that the bovine H5N1 virus has dual receptor-binding specificity, which may contribute to its ability to infect a broader range of hosts. These findings suggest that the HPAI H5N1 virus may pose a public health risk due to its potential to infect and transmit among mammals, including humans. The study highlights the need for further research to assess the risks posed by this virus to the human population.A 2024 outbreak of highly pathogenic avian influenza (HPAI) H5N1 virus in U.S. dairy cattle has raised concerns about its potential to infect and transmit among mammals. The virus, isolated from infected cow milk, was found to replicate systemically in mice and ferrets, including in mammary glands. It binds to both α2,3 and α2,6 sialic acid residues, enabling it to infect human-like respiratory tissues. However, transmission to ferrets via respiratory droplets was inefficient, with only one of four exposed ferrets showing seroconversion without detectable virus in nasal swabs. The virus can be transmitted from lactating mice to their pups through milk, but not to adult contact animals. The study also found that the bovine H5N1 virus has dual receptor-binding specificity, which may contribute to its ability to infect a broader range of hosts. These findings suggest that the HPAI H5N1 virus may pose a public health risk due to its potential to infect and transmit among mammals, including humans. The study highlights the need for further research to assess the risks posed by this virus to the human population.