Comprehensive analysis of transmission tropism and livestock epidemi ology of avian influenza viruses

Project summary

High pathogenicity avian influenza A viruses (HPAIV) are important pathogens threatening both animal welfare and human health. Since 2022, HPAIVs of the H5Nx subtype have become panzootic and continue to increase both their geographic spread and host range. Outbreaks in wild bird populations as well as poultry result in mass mortality leading to huge economic losses and potential spillovers to other species. In particular mammalian spillover infections are causing major concerns, as each case offers a chance for mammalian adaptation, thereby potentially increasing the zoonotic risk. The list of mammalian hosts infected with HPAIV is ever-expanding and in some cases, mammal-to-mammal transmission has been observed. Most recently, H5 HPAIV outbreaks in dairy cattle in the US have demonstrated the potential of these viruses to open new reservoirs for circulation. It is therefore of utmost importance to study these viruses, the potential hosts they can infect, and prevention measures to limit their future spread in livestock species.

This project is divided into 3 work packages. In WP1, we plan to study relevant H5 HPAIVs in molecular detail using in vitro assays to identify genetic markers of interest before validating and further characterizing them via reverse genetics. WP2 will focus on potential mammalian hosts, including cattle and pigs. As the mammary glands of lactating cows are known viral replication sites, we will study these using histopathology and transcriptomic approaches on mammary gland organoids and tissues from infected animals. In WP3, we will investigate the immune response against H5 HPAIV in pigs and lactating cattle after vaccination with three types of vaccine and compare to those from in vivo infected cattle and pigs.

With these research approaches we will gain a better understanding of these viruses and their systemic and local immune responses focusing on the mammary gland, which will aid preparedness against upcoming threats.