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The Orthobunyavirus genus of the Peribunyaviridae family, in the Bunyavirales order, groups together a large number of arthropod-borne viruses (arboviruses), with over 100 members worldwide, notably in Western Europe, North and South America and Asia. Many of these viruses are emerging pathogens that cause serious, sometimes fatal, illnesses in humans and large ruminants. The fact that orthobunyaviruses (OBVs), like other arboviruses, have a complex dual life cycle in arthropods and vertebrates, implies fundamental differences in the molecular composition of viral particles, whether produced from arthropod or mammalian cells. How the molecular characteristics acquired by OBV in arthropod vectors influence the infection of mammalian hosts remains largely to be discovered.

In this study, Colin used Germiston virus (GERV), a mosquito-transmitted neurotropic OBV, as a viral model system to study OBV host switch and the early stages of OBV infection of cells. Colin established a protocol to produce large quantities of purified GERV from mosquito and mammalian cells. Using these viruses, he discovered that GERVs derived from mosquito cells (mosGERV) are more infectious than those produced in mammalian cells (mamGERV) when infecting mammalian cells. In detail, both GERVs rely on intact late endosomal compartments for infectious entry, but viral binding appears to be more efficient and viral fusion more rapid when GERV is derived from mosquito rather than mammalian cells. It appeared that particles produced in mosquito cells display a high level of trimerization of the viral envelope glycoprotein Gc, conferring a more rapid ability to fuse. Colin also examined the molecular composition of GERV particles using lipidomic and proteomic analyses in collaboration with the University of Lyon and INRAE Clermont-Ferrand. These OMICS approaches revealed a distinct molecular composition of GERV particles produced in mosquito and mammalian cells.

Overall, Colin's results indicate that OBVs produced in mosquito cells are more infectious in mammalian cells than those produced in mammalian cells. The difference appears to be essentially due to the entry of viral particles into the cell. The results of Colin's thesis provide new insights into the vector-host transmission of arboviruses and valuable information on the molecular changes that occur during this transition. His work also lays the basis for developing new antiviral strategies against OBVs and related viruses.

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