Journal of NeuroVirology, 9: 577–583, 2003 c  2003 Journal of NeuroVirology ISSN: 1355-0284 print / 1538-2443 online DOI: 10.1080/13550280390247678 Mini Review A Mediterranean arbovirus: The Toscana virus Marcello Valassina, Maria Grazia Cusi, and Pier Egisto Valensin Department of Molecular Biology, Section of Virology, University of Siena, Siena, Italy Toscana virus (Bunyaviridae family, Phlebovirus genus) is a sandfly fever virus responsible for human neurological infections. Sandfly viruses are transmitted by insect vectors (Phlebotomus species) and the infection is present in climatic areas that allow the life cycle of the vector. The arthropode-borne Toscana virus is the etiologic agent of meningitis, meningoencephalitis, and encephalitis. The frequency of this neuropathic infection increases in the summer months, peak- ing in August in the endemic Mediterranean areas (Italy, Portugal, Spain, and Cyprus). Infection diagnosis is carried out by molecular assays and immunoen- zymatic tests, which are rapid and sensitive. Recent studies have investigated the antigenic properties of the viral proteins (nucleoprotein N and surface gly- coproteins G1 and G2), to better understand their immunogentic role. Journal of NeuroVirology (2003) 9, 577–583. Keywords: phlebovirus; serotype; Toscana Introduction Many viruses are transmitted to man through arthro- pods, and many species of insects are involved in numerous geographical areas. Among the types of arbovirus transmitted to man, the Bunyaviridae family is large and it is composed of five genera: Bunyavirus, Hantavirus, Nairovirus, Phlebovirus (associated with the Uukuvirus), and Tospovirus which recently generated great interest in the botanic field (Beaty and Calisher, 1991). The Phlebovirus genus includes 37 recognized viruses, such as the sandfly fever viruses, and are mostly transmitted to vertebrates by phlebotomine, although other arthropods are also recognized vectors (Nicoletti and Varani, 1985). Phleboviruses are geographically distributed in Europe, Africa, Central Asia, and the Americas (Gonzales-Scarano et al, 1991; Touny et al, 1989). Little is known about the host animal reservoir: isolation tests and serological assays have suggested some animal species as candidates, although it was not possible to define their effective reservoir roles. It seems that the role of the animal in the survival of the virus is secondary to the horizontal amplification of the virus, which is, how- ever, able to guarantee its transovaric and venereal Address correspondence to Prof. Pier Egisto Valensin, Depart- ment of Molecular Biology, Microbiology Section, University of Siena, Via Laterina, 8 53100 Siena, Italy. E-mail: valensinpe@ unisi.it Received 20 January 2003; revised 6 June 2003; accepted 30 July 2003. transmission (Tesh, 1988; Tesh and Modi, 1987; Tesh et al, 1992; Maroli et al, 1993). Among the viruses belonging to the Phlebovirus genus, Rift Valley virus and sandfly fever virus are the most important (Meegan and Bailey, 1988; Tesh et al, 1976). In the latter group, there are some viruses circulating in Europe, which are responsible for acute nonfatal, influenza-like symptomatology (Eitrem et al, 1991b; Hertig and Sabin, 1964). Among these strains, in Europe there are three circulating serotypes: Sicilian virus, Naples virus, and Toscana virus. The Sicilian and Naples viruses are also present in Central Asia and the Middle East and they have the same vector distribution. The Toscana virus is present in Italy, Algeria, Spain, Portugal, and Cyprus, as noted in studies of the indigenous population and cases of infection in tourists visiting these areas (Ehrnst et al, 1985; Calisher et al, 1987; Endris and Perkins 1987; Eitrem et al, 1990, 1991; Schwarz et al, 1993; Dobler et al, 1997). Toscana virus was initially isolated from Phlebotomus pernicious in central Italy in 1971 and in 1980 it was registered in the International Cata- logue of Arbovirus, and assigned to the Phlebovirus genus. Other strains of Toscana virus were isolated from Phlebotomus perfiliewi in other areas of Italy and from the brains of bats, Pipistrellus kuhli, cap- tured in areas where the insect vectors were present (Verani et al, 1982, 1984a, 1988; Ciufolini et al, 1985). Toscana virus presents a distinct neurovirulence, a characteristic that it shares with the Rift Valley virus: they are the only neurovirulent viruses of the Phlebovirus group. Different from the Sicilian and Neaples viruses, which cause a febrile disease