Abstract Title
Do animal models accurately reflect the risk of H5N1 infection in humans?
Abstract
This study investigated the zoonotic potential of a novel H5N1 influenza A virus, A/Texas/37/24, identified during a 2024 outbreak in US dairy cattle. We characterized the viral pathogenicity and replication kinetics in animal models and human respiratory cells.
In mice, A/Texas/37/24 caused 100% mortality within 5 days. Ferret inoculation studies, using both liquid intranasal and aerosol routes, resulted in mortality for all animals. Aerosol inoculation led to higher viral titers in respiratory tissues at early time points, suggesting more efficient viral spread. Widespread viral replication was observed in various organs, indicating systemic infection. A/Texas/37/24 replicated efficiently in human airway epithelial (HAE) cells following liquid inoculation. However, aerosol inoculation resulted in significantly reduced infectivity, raising questions about the efficiency of human-to-human transmission via this route. Our findings demonstrate the high pathogenicity of A/Texas/37/24 in mammals and its ability to replicate in human respiratory cells. The reduced infectivity observed following aerosol inoculation of HAE cells highlights the need for further research to understand viral transmission dynamics and accurately assess the risk of this H5N1 strain for humans. Overall, these results suggest that animal models potentially overestimate the pandemic risk of recent H5N1.
In mice, A/Texas/37/24 caused 100% mortality within 5 days. Ferret inoculation studies, using both liquid intranasal and aerosol routes, resulted in mortality for all animals. Aerosol inoculation led to higher viral titers in respiratory tissues at early time points, suggesting more efficient viral spread. Widespread viral replication was observed in various organs, indicating systemic infection. A/Texas/37/24 replicated efficiently in human airway epithelial (HAE) cells following liquid inoculation. However, aerosol inoculation resulted in significantly reduced infectivity, raising questions about the efficiency of human-to-human transmission via this route. Our findings demonstrate the high pathogenicity of A/Texas/37/24 in mammals and its ability to replicate in human respiratory cells. The reduced infectivity observed following aerosol inoculation of HAE cells highlights the need for further research to understand viral transmission dynamics and accurately assess the risk of this H5N1 strain for humans. Overall, these results suggest that animal models potentially overestimate the pandemic risk of recent H5N1.
Co-Author(s)
L. Claire Gay1, Flavio Cargnin Faccin1, C. Joaquin Caceres1, Teresa Mejias1, Dikshya Regmi1, and Daniel R. Perez1.
1Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Abstract Category
Avian influenza in mammals, pandemic preparedness, and one health