Activities of UBIVE are mainly focused on Arenavirus pathogenesis and immune responses. In vitro human models are used to compare closely related viruses that present different pathogenicity, Lassa (LASV) and Mopeia viruses (MOPV). We have identified host responses involved in these discrepancies. As there is no rodent model of Lassa fever (LF) that reproduces the disease observed in human, we have studied LF in non-human primates (NHP) and observed different immune responses associated with recovery or fatal disease. We now focus on the role of viral factors in the pathogenicity and immunogenicity induced during arenavirus infections. We developed a reverse genetic system for LASV and are establishing a similar system for MOPV to characterize the role of viral factors in pathogenicity and immunogenicity by fully exploiting the panel of possible constructs between LASV and MOPV by swapping coding or non-coding regions into each backbone. The host factors interacting with viral proteins are identified using yeast two-hybrid assays. Interactions are compared between LASV and MOPV but also between hosts presenting different sensitivity to LASV. Further studies will be realized in animal models to elucidate immune and pathogenic mechanisms associated with severe LF or viral control and to confirm the role of viral factors.
UBIVE hosts the National Reference Center (NRC) for Viral Hemorrhagic Fevers (VHF) and the NRC for Hantavirus, and leads the WHO collaborative center for VHF. NRC make the link between fundamental research and field/clinical investigations by providing new strains or agents and clinical specimens. NRC realize applied research and surveillance activities, such as development of diagnosis tools or exploration of viral diversity in wildlife. The NRC for Hantavirus surveys the dynamics of Hantavirus circulation in French population and in bank voles. This integrative and complementary approach including fundamental research and reference activities gives results that range from basic knowledge to field work and public health.

Key words: Viral hemorrhagic fever, Virology, Immunology, Lassa fever, Hantavirus, Diagnosis, Pathophysiology, Immune responses