Abstract
In order to prevent the emergence of infectious diseases, it is important to study and to better understand the interactions that exist between the different actors (human, virus, hosts/reservoirs, environment) involved in this process. We are interested in nephropathia epidemica (NE) and more particularly in its epidemiological situation in France where an extension of the geographical distribution of human cases has been decribed in recent years. France offers a particular situation with so-called endemic areas (many human cases of NE) and so-called non-endemic areas (few or no humans). However, the full set of actors used in these epidemiological differences is unknown. We are therefore interested in the interactions between the orthohantavirus Puumala, responsible for this zoonosis, and its reservoir, the bank voles, and in the eco-evolutionary processes that could influence the epidemiology of NE in France. Throughout the research work, we combined two complementary approaches: the first focused on virology and experimental infections in the laboratory, and the second focused on viral evolution and high-throughput sequencing techniques. We are focused on two French areas with contrasting NE epidemiological patterns, the Ardennes (endemic area) and Loiret (non-endemic area), where the virus is also known to circulate in rodent populations. We first carried out a synthesis of studies on experiments with orthohantaviruses and their reservoirs. This allowed us to take up the major research themes addressed on this subject and to identify the limits and perspectives that can be considered on these host-pathogen pairs. Then we describe how we succeeded in isolating for the first time the PUUV strains circulating in the Ardennes and the Loiret as well as their characterization on laboratory rodents. Finally, we describe how the interactions between PUUV and its wild reservoir affect eco-evolutionary processes (serological response, replication, viral diversity) which in turn can influence the epidemiology of NE. In conclusion, this thesis allowed us to highlight the importance of the variability of PUUV strains in the epidemiology of NE and the role that the reservoir could also have.