title: Development of a mouse model for the study of Toscana virus pathogenesis.
abstract: Toscana virus (TOSV) has recently been recognized as an emerging virus transmitted by phlebotomus vectors, responsible for acute neurological diseases in Mediterranean countries. In our study, we demonstrated that adult Balb/c mice were susceptible to TOSV when infected intracerebrally (i.c.) or subcutaneously (s.c.) with a neuroadapted strain of the virus. We have shown that by performing serial passages of a wild type human isolate of TOSV in mouse brains, selection occurs for a highly virulent variant which replicates efficiently in the central nervous system (CNS) of i.c.-injected mice, causing acute encephalitis and death. Immunohistochemical analysis and TUNEL assay of post-mortem organs showed that TOSV replication was highly restricted to neurons in which it induced apoptotic death; however, virus antigen-positivity was also observed in the spleen and lymph nodes. In s.c.-injected mice, virus was detectable in the spleen and lymph nodes, whereas only few meningeal cells and neurons were affected, allowing for the mouse survival the infection. The presence of TOSV in spleen and lymph node cells in both s.c.- and i.c.-treated mice suggests their possible involvement in the diffusion of the infection. This animal model may be helpful for the development of prophylactic measures against TOSV infections.
authors.affiliation: Department of Molecular Biology, Virology Section, University of Siena, Policlinico Le Scotte, V.le Bracci, Building V, 53100 Siena, Italy. cusi@unisi.it
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cusi
authors.forename: Gianni
authors.initials: G
authors.lastname: Gori Savellini
authors.forename: Chiara
authors.initials: C
authors.lastname: Terrosi
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Di Genova
authors.forename: Marcello
authors.initials: M
authors.lastname: Valassina
authors.forename: Melissa
authors.initials: M
authors.lastname: Valentini
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bartolommei
authors.forename: Clelia
authors.initials: C
authors.lastname: Miracco
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001921:Brain / Q000473:pathology / Q000821:virology; D002044:Bunyaviridae Infections / Q000276:immunology / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D029301:Sandfly fever Naples virus / Q000276:immunology / Q000472:pathogenicity*; D014766:Viremia; D014779:Virus Replication