Abstract
In Europe, many flaviviruses are endemic (West Nile, Usutu, tick-borne encephalitis viruses) or occasionally imported (dengue, yellow fever viruses). Due to the temporal and geographical co-circulation of flaviviruses in Europe, flavivirus differentiation by diagnostic tests is crucial in the adaptation of surveillance and control efforts. Serological diagnosis of flavivirus infections is complicated by the antigenic similarities among the Flavivirus genus. Indeed, most flavivirus antibodies are directed against the highly immunogenic envelope protein, which contains both flavivirus cross-reactive and virus-specific epitopes. Serological assay results should thus be interpreted with care and confirmed by comparative neutralization tests using a panel of viruses known to circulate in Europe. However, antibody cross-reactivity could be advantageous in efforts to control emerging flaviviruses because it ensures partial cross-protection. In contrast, it might also facilitate subsequent diseases, through a phenomenon called antibody-dependent enhancement mainly described for dengue virus infections. Here, we review the serological methods commonly used in WNV diagnosis and surveillance in Europe. By examining past and current epidemiological situations in different European countries, we present the challenges involved in interpreting flavivirus serological tests and setting up appropriate surveillance programs; we also address the consequences of flavivirus circulation and vaccination for host immunity.
Highlights
IntroductionWest Nile virus (WNV) is a widespread re-emerging pathogen that belongs to the Flaviviridae family and Flavivirus genus and is one of the most threatening flaviviruses in Europe (for a recent review see [1])
West Nile virus (WNV) is a widespread re-emerging pathogen that belongs to the Flaviviridae family and Flavivirus genus and is one of the most threatening flaviviruses in Europe.This arbovirus is transmitted by mosquitoes in a cycle in which different species of birds act as reservoir hosts, amplifying the virus
These animal models illustrate that prior immunization with heterologous flaviviruses and a challenge with a virulent strain generally induce immune booster effects, marked by an increase in neutralizing antibodies, a reduction or absence of the viremic phase after challenge, and subsequent complete or partial clinical protection
Summary
West Nile virus (WNV) is a widespread re-emerging pathogen that belongs to the Flaviviridae family and Flavivirus genus and is one of the most threatening flaviviruses in Europe (for a recent review see [1]) This arbovirus is transmitted by mosquitoes in a cycle in which different species of birds act as reservoir hosts, amplifying the virus. The interpretation of serological test results may be even more problematic when investigating infections caused by flaviviruses belonging to the same serocomplex, such as WNV and USUV in Europe, since cross-neutralization will be observed. In such situations, comparative VNTs that include every flavivirus suspected to circulate within a given area are called for. Most studies investigating flavivirus cross-protection or infection facilitation have found that prior infection or vaccination with heterologous flaviviruses should provide partial protection against WNV, with more efficient protection being provided by more closely related viruses
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