PARTNERSHIP:Harnessing Bovine Organoids to Advance HPAI Influenza A Virus Research

The emergence of High Pathogenicity Avian Influenza (HPAI) H5N1 in U.S. dairy cattle poses significant challenges, and raises concerns about animal health, milk production, and economic stability within the dairy industry. This research aims to mitigate the impact of influenza virus infections in dairy cow populations by developing organoid models from bovine respiratory, intestinal, and mammary tissues. These organoids will facilitate essential studies on the virus-host interactions that underpin HPAI pathogenesis, an area critically understudied due to the constraints of agricultural BSL3+ facilities. Historical data indicate that HPAI predominantly affects poultry, yet recent spillover events have demonstrated its ability to infect mammals, including cattle, highlighting potential zoonotic risks. Notably, the viral tropism in bovine hosts remains poorly defined, with high viral loads observed in mammary tissues and milk, while the presence of the virus in the respiratory tract remains contentious. Utilizing organoid technology, this study will explore the variable pathogenesis of IAV across different bovine tissues and assess the impact of cellular heterogeneity on viral infection and host responses. Additionally, the role of specific host pathways, such as the Rab11-mediated genome trafficking pathway, in the adaptation and virulence of HPAI will be investigated. Overall, this research addresses critical gaps in understanding HPAI in bovine hosts, aiming to inform future surveillance and control strategies to prevent further outbreaks and safeguard both public health and agricultural interests.