Genetic diversity of Toscana virus glycoproteins affects the kinetics of virus entry and the infectivity of newly produced virions

Toscana virus (TOSV) is a pathogenic and transmissible Phlebovirus of the Bunyavirales order. To date, two principal genetic lineages (A and B) have been identified and the impact of TOSV genetic diversity on its biology is still unknown. We used a reverse genetic approach based on two TOSV strains belonging to lineage A or B (i.e., TOSV-A and TOSV-B) and displaying different in vitro replicative fitness. Our results demonstrate that the sequences of Gn and Gc glycoproteins are responsible for the differences in replicative fitness between the two TOSV strains. Moreover, our data show that TOSV-A and TOSV-B display different entry kinetics and that newly-produced virions have different infectivity. This comparative approach demonstrates that the genetic diversity of TOSV can significantly impact viral properties and highlights the need for better molecular characterisation of the genomes of circulating TOSV strains, with a particular focus on the viral Gn and Gc glycoproteins.