Abstract:The Flavivirus genus (Flaviviridae family) contains important pathogens such as yellow fever virus, Japanese encephalitis virus, St Louis encephalitis virus, West Nile virus, Usutu virus (USUV), Zika virus, and dengue virus, many of which constitute a worrisome threat to global human and animal health. USUV is transmitted by mosquitoes and, as any other flavivirus, is an enveloped plus-strand RNA virus. The virus was first isolated from Culex neavei mosquitoes in South Africa in 1959 near the Usutu River, from where it takes its name. Since then, the virus was confined to Africa until its first detection in Austria in 2001, although it was probably present in Europe since 1996 or even earlier. After that, USUV has spread throughout Europe, causing a considerable mortality among birds and a few neurologic cases in humans. The main USUV natural hosts are birds, but infection has also been reported in other vertebrate species, including humans. The fast spread of the virus through the continent, the relatively high mortality caused in birds, and the recent neuroinvasive human cases related to USUV infection reported in Europe have raised serious concerns about its possible consequences for public health. Here, an updated review of current knowledge about this emerging pathogen is presented. Keywords: Usutu virus, flavivirus, host cell-virus interactions, surveillance, prophylaxis
Biology of the virus Molecular classification and phylogenyUsutu virus (USUV) is a member of the Flavivirus genus within the Flaviviridae family ( Figure 1A). In 2004, the complete genomic sequences of two USUV strains, one African (South Africa-1959) and one European (Vienna-2001), were used to build a phylogenetic tree. These two strains showed a 97% and 99% homology at the nucleotide (nt) and amino acid (aa) level, respectively.1 Both strains were closely related to Murray valley encephalitis virus (73% and 82% nt and aa similarity), Japanese encephalitis virus (71% and 81% nt and aa similarity), and to West Nile virus (WNV; 68% and 75% nt and aa similarity). Nowadays, dozens of complete sequences are available in the data banks. In a recent study, the sequence identity among seven USUV strains was 96%-99% and 99% at the nt and aa levels, respectively.2 The only exception was a 1969 isolate from Central African Republic (CAR-1969) that presented homologies of 81% and 94% at the nt and aa levels with other African sequences ( Figure 1B). Due to these differences, it has been suggested that CAR-1969 formed an USUV subtype strain.3 A comparison with the original South African SAAR-1776 strain showed that the mutations found among different European and African strains were scattered throughout the genome, with some unique substitutions and some that were present