Abstract
During the last decade, the epidemiology of WNV in humans has changed in the southern regions of Europe, with high incidence of West Nile fever (WNF) cases, but also of West Nile neuroinvasive disease (WNND). The lack of human vaccine or specific treatment against WNV infection imparts a pressing need to characterize indicators associated with neurological involvement. By its intimacy with central nervous system (CNS) structures, modifications in the cerebrospinal fluid (CSF) composition could accurately reflect CNS pathological process. Until now, few studies investigated the association between imbalance of CSF elements and severity of WNV infection. The aim of the present study was to apply the iTRAQ technology in order to identify the CSF proteins whose abundances are modified in patients with WNND. Forty-seven proteins were found modified in the CSF of WNND patients as compared to control groups, and most of them are reported for the first time in the context of WNND. On the basis of their known biological functions, several of these proteins were associated with inflammatory response. Among them, Defensin-1 alpha (DEFA1), a protein reported with anti-viral effects, presented the highest increasing fold-change (FC>12). The augmentation of DEFA1 abundance in patients with WNND was confirmed at the CSF, but also in serum, compared to the control individual groups. Furthermore, the DEFA1 serum level was significantly elevated in WNND patients compared to subjects diagnosed for WNF. The present study provided the first insight into the potential CSF biomarkers associated with WNV neuroinvasion. Further investigation in larger cohorts with kinetic sampling could determine the usefulness of measuring DEFA1 as diagnostic or prognostic biomarker of detrimental WNND evolution.
Highlights
West Nile virus (WNV) belongs to the Flaviviridae family, transmitted to humans by the bite of infectious mosquitoes, mainly from the Culex genus [1]
Humans and equines are sensitive to WNV infection, but they are considered as incidental dead-end hosts, due to the low and short viremia [3].While the majority of humans infected with WNV remain asymptomatic, approximately 20% develop a transient febrile illness, known as West Nile fever (WNF); and about 1% of infected individuals develop a neuroinvasive disease (WNND) characterized by encephalitis, meningitis, and/or acute flaccid paralysis, leading in some cases to a fatal outcome [4,5]
In 2010, the first large outbreak of WNV infections occurred in Greece [7]; it was characterized by the census of nearly 200 West Nile neuroinvasive disease (WNND) cases with 17%
Summary
West Nile virus (WNV) belongs to the Flaviviridae family (genus Flavivirus), transmitted to humans by the bite of infectious mosquitoes, mainly from the Culex genus [1]. The epidemiology of WNV has changed in the more southern regions of Europe, with increased incidence of WNND in humans [6]. In 2010, the first large outbreak of WNV infections occurred in Greece [7]; it was characterized by the census of nearly 200 WNND cases with 17%. The recent epidemiologic studies underline that in Europe, like in the United States, WNV infections, and WNND cases, have become of major public health concern [13]. Despite the development of successful WNV vaccines for equines and the ongoing clinical trials for human vaccines, no licensed vaccine for human use is currently available [5]. Currently no specific antiviral treatment for WNV infections is available and only supportive care is administered.
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