Transcriptomic profile of chicken monocyte derived dendritic cells in response to H5N1 highly pathogenic avian influenza virus infection

Since 2021, clade 2.3.4.4b H5N1 highly pathogenic avian influenza viruses (HPAIVs) have become the most predominant worldwide. These viruses are associated with high mortality rates in poultry and wild birds, leading to sporadic spill-over infections in humans and other mammals. Notably, aquatic wild birds, such as Anseriformes and Charadriiformes, act as the natural reservoir for avian influenza A viruses (AIVs) and were historically asymptomatic upon AIV infection. However, current clade 2.3.4.4b viruses induce severe symptoms and high mortality rates in infected waterfowl. Within the framework of the WiLiMan-ID project, our main goal is to gain insight into the mechanisms that shape host-pathogen interactions and contribute to a higher HPAIV virulence. To this end, an ex vivo HPAIV infection model was developed using chicken dendritic cells, key antigen-presenting cells that play a crucial role in triggering both innate and adaptive immune responses. More specifically, the transcriptomic profile of monocyte-derived dendritic cells (MoDCs) was investigated 6 hours post-infection with two H5N1 HPAIV strains: a 2023 isolate belonging to clade 2.3.4.4b (genotype AB), and a 2013 strain from clade 2.3.2.1c. This second virus historically showed a lower virulence in waterfowls and also exhibited a significantly reduced replication in our model. Transcriptomic profiling of the infected MoDCs revealed over 17,000 differentially expressed genes when compared to mock-infected controls, including many involved in immune pathways. Additionally, significant differences were observed in the expression profiles of immune-related genes induced by these two HPAIV strains when evaluated by RT-qPCR. These results represent an important first step towards identifying host cellular factors that could be responsible for the increased virulence of recent H5N1 HPAIVs.