Reassortment, Emergence and Factor of Virulence of Influenza A Virus – REACTIV

Influenza A viruses are amongst the most challenging viruses for both human and animal health. The diversity of hosts that they can infect and the frequency of inter-species transmission events maintain the threat of the emergence of strains with high efficiency of spread among humans that could result in pandemics. Since 2013, H5Nx reassortants viruses (derived from HPAI H5N1clade 2.3.4.4 viruses) spread panzootically all over the world. In France, the H5N8 strain resulted in the culling of millions of ducks and in massive economic losses for the poultry industry. Our project aims at a better understanding of the emergence of reassortants viruses from the avian reservoir and notably of the role of the segment 2, encoding PB1, the viral polymerase and the factor of virulence PB1-F2. Taking advantage of this natural reassortment event, we propose to combine different approaches to study this phenomenon occurring in the field: a phylogenetic analysis of segment 2 of avian viruses and a characterization of its ability to emerge by reassortment events, a study of the role of PB1-F2 on pathogenicity and transmission ability of the reassortants viruses (using H5N8 Tarn virus and its variants produced by reverse genetic). The propensity of fibrillization of avian PB1-F2 will be assessed in vitro. Using mouse and duck models of infection, the pathogenic potential of PB1-F2 and the inflammatory response of the host will be explored in order to decipher the mechanism of action of PB1-F2. Finally, the detection of PB1-F2 fibers will be performed at the single-cell level and in animal models (infected tissues) using innovative methods (synchrotron experiments).