Experimental infection and viral pathogenesis of a human isolate of H5N1 highly pathogenic avian influenza strain in Jersey cows

Highly pathogenic avian influenza H5N1 viruses have circulated globally since 1996. In recent years, clade 2.3.4.4b H5N1 viruses have crossed the species barrier into multiple species, including dairy cattle, causing a significant decrease in milk production and rapid spread across multiple U.S. states in 2024. Previous studies have demonstrated that Holstein cows are susceptible to H5N1 infection in laboratory settings, mirroring field observations. To investigate whether Jersey cows are susceptible to H5N1 infection and their potential as an experimental model, we inoculated three Jersey lactating cows intranasally and intramammarily with a human H5N1 influenza virus. Following inoculation, milk production rapidly decreased, and milk samples exhibited a colostrum-like yellow appearance. Milk production remained low for at least seven days. All three cows experienced high fever peaks within one day of inoculation. California Mastitis Test scores in milk samples from infected quarters were elevated for several days. Infection was confirmed by high levels of viral RNA detected for several days in external and internal swabs of infected teats, and milk samples. Conversely, low levels of viral RNA were detected in the respiratory tract of infected cows. These findings confirm that Jersey cows are susceptible to H5N1 infection and establish them as a valuable experimental model for studying disease pathogenesis and developing effective vaccines.