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West Nile Virus 2019
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West Nile Virus 2019

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 67310

Special Issue Editor

Prof. Dr. Norbert Nowotny

E-Mail Website
Guest Editor
1. Viral Zoonoses, Emerging and Vector-Borne Infections Group, Institute of Virology, University of Veterinary Medicine, Vienna, Austria
2. College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
Interests: vector-borne viruses; emerging viruses; viral zoonoses; viruses at the environment/animal/human interface; West Nile virus; Usutu virus; Borna disease virus; MERS and SARS coronaviruses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

West Nile virus (WNV) is the most widespread flavivirus present in all continents, except Antarctica. It is also a truly emerging virus, which 20 years ago was absent in the Americas and had little impact in Europe. This changed significantly when lineage 1 WNV was introduced to the United States in 1999, followed by the emergence of two different lineage 2 WNVs in Europe around 2004. After an adaptation period of a few years, the newly introduced viruses spread quickly across the Americas and Europe. Humans, horses, and birds have been confirmed to be susceptible hosts for WNV, with clinical symptoms ranging from mild to life-threatening neuro-invasive West Nile disease. In 2018, Europe experienced an upsurge in the number of WNV infections. Similarly, in the U.S., more human cases were seen in 2018 when compared to the previous year(s). The natural transmission cycle of WNV involves certain mosquito species, mainly Culex, and a number of avian species. Since transmission-competent mosquito species are abundantly found in cooler climatic regions, further dispersal of the virus is likely.

In this Special Issue, we welcome research papers and review articles related to all aspects of WNV research, providing an update of our knowledge of WNV. Topics of interest include (but are not limited to) virus genetics, epidemiology, virus–host interactions, pathogenesis, vaccine development, improvement in diagnostics, as well as vector entomology.

Prof. Dr. Norbert Nowotny
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • West Nile virus
  • West Nile fever
  • West Nile neuroinvasive disease
  • epidemiology
  • phylogeny
  • virus genetics
  • blood donations
  • diagnostic challenges
  • related flaviviruses
  • One Health

Published Papers (15 papers)

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Research

Jump to: Review, Other

18 pages, 8994 KiB  
Article
Autochthonous Transmission of West Nile Virus by a New Vector in Iran, Vector-Host Interaction Modeling and Virulence Gene Determinants
by Nariman Shahhosseini, Seyed Hassan Moosa-Kazemi, Mohammad Mehdi Sedaghat, Gary Wong, Sadegh Chinikar, Zahra Hajivand, Hamid Mokhayeri, Norbert Nowotny and Mohammad Hassan Kayedi
Viruses 2020, 12(12), 1449; https://0-doi-org.brum.beds.ac.uk/10.3390/v12121449 - 16 Dec 2020
Cited by 9 | Viewed by 2284
Abstract
Using molecular techniques and bioinformatics tools, we studied the vector-host interactions and the molecular epidemiology of West Nile virus (WNV) in western Iran. Mosquitoes were collected during 2017 and 2018. DNA typing assays were used to study vector-host interactions. Mosquitoes were screened by [...] Read more.
Using molecular techniques and bioinformatics tools, we studied the vector-host interactions and the molecular epidemiology of West Nile virus (WNV) in western Iran. Mosquitoes were collected during 2017 and 2018. DNA typing assays were used to study vector-host interactions. Mosquitoes were screened by RT-PCR for the genomes of five virus families. WNV-positive samples were fully sequenced and evolutionary tree and molecular architecture were constructed by Geneious software and SWISS-MODEL workspace, respectively. A total of 5028 mosquito specimens were collected and identified. The most prevalent species was Culex (Cx.) pipiens complex (57.3%). Analysis of the blood-feeding preferences of blood-fed mosquitoes revealed six mammalian and one bird species as hosts. One mosquito pool containing non-blood-fed Cx. theileri and one blood-fed Culex pipiens pipiens (Cpp.) biotype pipiens were positive for WNV. A phylogram indicated that the obtained WNV sequences belonged to lineage 2, subclade 2 g. Several amino acid substitutions suspected as virulence markers were observed in the Iranian WNV strains. The three-dimensional structural homology model of the E-protein identified hot spot domains known to facilitate virus invasion and neurotropism. The recent detection of WNV lineage 2 in mosquitoes from several regions of Iran in consecutive years suggests that the virus is established in the country. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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20 pages, 3636 KiB  
Article
Modelling West Nile Virus and Usutu Virus Pathogenicity in Human Neural Stem Cells
by Silvia Riccetti, Alessandro Sinigaglia, Giovanna Desole, Norbert Nowotny, Marta Trevisan and Luisa Barzon
Viruses 2020, 12(8), 882; https://0-doi-org.brum.beds.ac.uk/10.3390/v12080882 - 12 Aug 2020
Cited by 14 | Viewed by 3615
Abstract
West Nile virus (WNV) and Usutu virus (USUV) are genetically related neurotropic mosquito-borne flaviviruses, which frequently co-circulate in nature. Despite USUV seeming to be less pathogenic for humans than WNV, the clinical manifestations induced by these two viruses often overlap and may evolve [...] Read more.
West Nile virus (WNV) and Usutu virus (USUV) are genetically related neurotropic mosquito-borne flaviviruses, which frequently co-circulate in nature. Despite USUV seeming to be less pathogenic for humans than WNV, the clinical manifestations induced by these two viruses often overlap and may evolve to produce severe neurological complications. The aim of this study was to investigate the effects of WNV and USUV infection on human induced pluripotent stem cell-derived neural stem cells (hNSCs), as a model of the neural progenitor cells in the developing fetal brain and in adult brain. Zika virus (ZIKV), a flavivirus with known tropism for NSCs, was used as the positive control. Infection of hNSCs and viral production, effects on cell viability, apoptosis, and innate antiviral responses were compared among viruses. WNV displayed the highest replication efficiency and cytopathic effects in hNSCs, followed by USUV and then ZIKV. In these cells, both WNV and USUV induced the overexpression of innate antiviral response genes at significantly higher levels than ZIKV. Expression of interferon type I, interleukin-1β and caspase-3 was significantly more elevated in WNV- than USUV-infected hNSCs, in agreement with the higher neuropathogenicity of WNV and the ability to inhibit the interferon response pathway. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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21 pages, 4709 KiB  
Article
Mosquito-Independent Transmission of West Nile virus in Farmed Saltwater Crocodiles (Crocodylus porosus)
by Gervais Habarugira, Jasmin Moran, Agathe M.G. Colmant, Steven S. Davis, Caitlin A. O’Brien, Sonja Hall-Mendelin, Jamie McMahon, Glen Hewitson, Neelima Nair, Jean Barcelon, Willy W. Suen, Lorna Melville, Jody Hobson-Peters, Roy A. Hall, Sally R. Isberg and Helle Bielefeldt-Ohmann
Viruses 2020, 12(2), 198; https://0-doi-org.brum.beds.ac.uk/10.3390/v12020198 - 11 Feb 2020
Cited by 12 | Viewed by 3632
Abstract
West Nile virus, Kunjin strain (WNVKUN) is endemic in Northern Australia, but rarely causes clinical disease in humans and horses. Recently, WNVKUN genomic material was detected in cutaneous lesions of farmed saltwater crocodiles (Crocodylus porosus), but live virus [...] Read more.
West Nile virus, Kunjin strain (WNVKUN) is endemic in Northern Australia, but rarely causes clinical disease in humans and horses. Recently, WNVKUN genomic material was detected in cutaneous lesions of farmed saltwater crocodiles (Crocodylus porosus), but live virus could not be isolated, begging the question of the pathogenesis of these lesions. Crocodile hatchlings were experimentally infected with either 105 (n = 10) or 104 (n = 11) TCID50-doses of WNVKUN and each group co-housed with six uninfected hatchlings in a mosquito-free facility. Seven hatchlings were mock-infected and housed separately. Each crocodile was rotationally examined and blood-sampled every third day over a 3-week period. Eleven animals, including three crocodiles developing typical skin lesions, were culled and sampled 21 days post-infection (dpi). The remaining hatchlings were blood-sampled fortnightly until experimental endpoint 87 dpi. All hatchlings remained free of overt clinical disease, apart from skin lesions, throughout the experiment. Viremia was detected by qRT-PCR in infected animals during 2–17 dpi and in-contact animals 11–21 dpi, indicating horizontal mosquito-independent transmission. Detection of viral genome in tank-water as well as oral and cloacal swabs, collected on multiple days, suggests that shedding into pen-water and subsequent mucosal infection is the most likely route. All inoculated animals and some in-contact animals developed virus-neutralizing antibodies detectable from 17 dpi. Virus-neutralizing antibody titers continued to increase in exposed animals until the experimental endpoint, suggestive of persisting viral antigen. However, no viral antigen was detected by immunohistochemistry in any tissue sample, including from skin and intestine. While this study confirmed that infection of saltwater crocodiles with WNVKUN was associated with the formation of skin lesions, we were unable to elucidate the pathogenesis of these lesions or the nidus of viral persistence. Our results nevertheless suggest that prevention of WNVKUN infection and induction of skin lesions in farmed crocodiles may require management of both mosquito-borne and water-borne viral transmission in addition to vaccination strategies. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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11 pages, 839 KiB  
Article
West Nile or Usutu Virus? A Three-Year Follow-Up of Humoral and Cellular Response in a Group of Asymptomatic Blood Donors
by Elena Percivalle, Irene Cassaniti, Antonella Sarasini, Francesca Rovida, Kodjo Messan Guy Adzasehoun, Ilaria Colombini, Paola Isernia, Irene Cuppari and Fausto Baldanti
Viruses 2020, 12(2), 157; https://0-doi-org.brum.beds.ac.uk/10.3390/v12020157 - 29 Jan 2020
Cited by 38 | Viewed by 3112
Abstract
West Nile virus (WNV) and Usutu virus (USUV) are two related arboviruses (genus Flavivirus, family Flaviviridae), with birds as a reservoir and mosquitoes as transmitting vectors. In recent years, WNV epidemiology changed in many European countries with increased frequency of outbreaks [...] Read more.
West Nile virus (WNV) and Usutu virus (USUV) are two related arboviruses (genus Flavivirus, family Flaviviridae), with birds as a reservoir and mosquitoes as transmitting vectors. In recent years, WNV epidemiology changed in many European countries with increased frequency of outbreaks posing the issue of virus transmission risks by blood transfusion. USUV emerged for the first time in birds of the Tuscany region (Italy) in 1996 and in 2001 in Austria. While WNV is responsible for both mild and neuroinvasive diseases, USUV infection is usually asymptomatic and neuroinvasive symptoms are rare. Since WNV and USUV co-circulate, the surveillance of WNV allows also the detection of USUV. Due to the great similarity in amino-acid sequence of major surface proteins of the two viruses, a high cross-reactivity can lead to misinterpretation of serological results. Here, we report the results obtained from 54 asymptomatic blood donors during a three-year follow-up showing an unexpected high positivity (46.3%) for USUV. The major obstacle encountered in the differential diagnosis between these two viruses was the high cross-reactivity found in neutralizing antibodies (NT Abs) and, in some cases, a long follow-up was mandatory for a correct diagnosis. Moreover, two new ELISpot assays were developed for a more rapid and specific differential diagnosis, especially in those cases in which NT Abs were not determinant. Using a combination of Enzyme-linked immunospot (ELISpot), molecular, and serological tests, we could identify 25 true positive WNV and 25 true positive USUV blood donors. Our data highlight the importance of raising awareness for increasing USUV infections in endemic countries involved in blood transfusion and organ donation. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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Graphical abstract

7 pages, 463 KiB  
Communication
Imported Human West Nile Virus Lineage 2 Infection in Spain: Neurological and Gastrointestinal Complications
by María Velasco, María Paz Sánchez-Seco, Carolina Campelo, Fernando de Ory, Oriol Martin, Laura Herrero, Octavio J. Salmerón Béliz, Teodora Minguito, Mª Carmen Campos, Francisca Molero, Alejandro Algora and Ana Vázquez
Viruses 2020, 12(2), 156; https://0-doi-org.brum.beds.ac.uk/10.3390/v12020156 - 29 Jan 2020
Cited by 3 | Viewed by 2058
Abstract
We report the first human case of West Nile virus (WNV) lineage 2 infection imported to Spain by a traveler returning from Romania. Serum, cerebrospinal fluid and urine samples were analyzed and West Nile virus infection was identified by PCR and serological tests. [...] Read more.
We report the first human case of West Nile virus (WNV) lineage 2 infection imported to Spain by a traveler returning from Romania. Serum, cerebrospinal fluid and urine samples were analyzed and West Nile virus infection was identified by PCR and serological tests. The patient developed fever, diarrhea and neurological symptoms, accompanied by mild pancreatitis, described previously in very few cases as a complication of WNV infection and by alithiasic cholecystitis. Viral RNA was detected in urine until 30 days after the onset of symptoms and neutralizing antibodies were detected at very low titers. The phylogenetic analysis in a fragment of the NS5 gene of the virus showed a homology with sequences from WNV lineage 2 belonging to the monophyletic Central/Southern European group. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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14 pages, 2048 KiB  
Article
Cellular microRNA-155 Regulates Virus-Induced Inflammatory Response and Protects against Lethal West Nile Virus Infection
by Janhavi P. Natekar, Hussin A. Rothan, Komal Arora, Philip G. Strate and Mukesh Kumar
Viruses 2020, 12(1), 9; https://0-doi-org.brum.beds.ac.uk/10.3390/v12010009 - 19 Dec 2019
Cited by 29 | Viewed by 4693
Abstract
West Nile virus (WNV) is a flavivirus that has disseminated globally as a significant cause of viral encephalitis in humans. MircoRNA-155 (miR-155) regulates various aspects of innate and adaptive immune responses. We previously reported that WNV infection induces upregulation of miR-155 in mice [...] Read more.
West Nile virus (WNV) is a flavivirus that has disseminated globally as a significant cause of viral encephalitis in humans. MircoRNA-155 (miR-155) regulates various aspects of innate and adaptive immune responses. We previously reported that WNV infection induces upregulation of miR-155 in mice brains. In the current study, we demonstrate the critical role of miR-155 in restricting the pathogenesis of WNV infection in mice. Compared to wild-type (WT) mice, miR-155 knockout mice exhibited significantly higher morbidity and mortality after infection with either a lethal strain, WNV NY99, or a non-lethal strain, WNV Eg101. Increased mortality in miR-155−/− mice was associated with significantly high WNV burden in the serum and brains. Protein levels of interferon (IFN)-α in the serum and brains were higher in miR-155−/− mice. However, miR-155−/− mice exhibited significantly lower protein levels of anti-viral interleukin (IL)-1β, IL-12, IL-6, IL-15, and GM-CSF despite the high viral load. Primary mouse cells lacking miR-155 were more susceptible to infection with WNV compared to cells derived from WT mice. Besides, overexpression of miR-155 in human neuronal cells modulated anti-viral cytokine response and resulted in significantly lower WNV replication. These data collectively indicate that miR-155 restricts WNV production in mouse and human cells and protects against lethal WNV infection in mice. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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20 pages, 6494 KiB  
Article
Remodeling of the Actin Network Associated with the Non-Structural Protein 1 (NS1) of West Nile Virus and Formation of NS1-Containing Tunneling Nanotubes
by Wilhelm Furnon, Pascal Fender, Marie-Pierre Confort, Sophie Desloire, Sawitree Nangola, Kuntida Kitidee, Caroline Leroux, Maxime Ratinier, Frédérick Arnaud, Sylvie Lecollinet, Pierre Boulanger and Saw-See Hong
Viruses 2019, 11(10), 901; https://0-doi-org.brum.beds.ac.uk/10.3390/v11100901 - 27 Sep 2019
Cited by 7 | Viewed by 4199
Abstract
The cellular response to the recombinant NS1 protein of West Nile virus (NS1WNV) was studied using three different cell types: Vero E6 simian epithelial cells, SH-SY5Y human neuroblastoma cells, and U-87MG human astrocytoma cells. Cells were exposed to two different forms [...] Read more.
The cellular response to the recombinant NS1 protein of West Nile virus (NS1WNV) was studied using three different cell types: Vero E6 simian epithelial cells, SH-SY5Y human neuroblastoma cells, and U-87MG human astrocytoma cells. Cells were exposed to two different forms of NS1WNV: (i) the exogenous secreted form, sNS1WNV, added to the extracellular milieu; and (ii) the endogenous NS1WNV, the intracellular form expressed in plasmid-transfected cells. The cell attachment and uptake of sNS1WNV varied with the cell type and were only detectable in Vero E6 and SH-SY5Y cells. Addition of sNS1WNV to the cell culture medium resulted in significant remodeling of the actin filament network in Vero E6 cells. This effect was not observed in SH-SY5Y and U-87MG cells, implying that the cellular uptake of sNS1WNV and actin network remodeling were dependent on cell type. In the three cell types, NS1WNV-expressing cells formed filamentous projections reminiscent of tunneling nanotubes (TNTs). These TNT-like projections were found to contain actin and NS1WNV proteins. Interestingly, similar actin-rich, TNT-like filaments containing NS1WNV and the viral envelope glycoprotein EWNV were also observed in WNV-infected Vero E6 cells. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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15 pages, 2136 KiB  
Article
Evolutionary Dynamics of the Lineage 2 West Nile Virus That Caused the Largest European Epidemic: Italy 2011–2018
by Carla Veo, Carla della Ventura, Ana Moreno, Francesca Rovida, Elena Percivalle, Sabrina Canziani, Debora Torri, Mattia Calzolari, Fausto Baldanti, Massimo Galli and Gianguglielmo Zehender
Viruses 2019, 11(9), 814; https://0-doi-org.brum.beds.ac.uk/10.3390/v11090814 - 03 Sep 2019
Cited by 28 | Viewed by 4280
Abstract
Lineage 2 West Nile virus (WNV) caused a vast epidemic in Europe in 2018, with the highest incidence being recorded in Italy. To reconstruct the evolutionary dynamics and epidemiological history of the virus in Italy, 53 envelope gene and 26 complete genome sequences [...] Read more.
Lineage 2 West Nile virus (WNV) caused a vast epidemic in Europe in 2018, with the highest incidence being recorded in Italy. To reconstruct the evolutionary dynamics and epidemiological history of the virus in Italy, 53 envelope gene and 26 complete genome sequences obtained from human and animal samples were characterised by means of next-generation sequencing. Phylogenetic analysis revealed two Italian strains originating between 2010 and 2012: clade A, which apparently became extinct in 2013–2014, and clade B, which was responsible for the 2018 epidemic. The mean genetic distances in clade B increased over time and with the distance between sampling locations. Bayesian birth-death and coalescent skyline plots of the clade B showed that the effective number of infections and the effective reproduction number (Re) increased between 2015 and 2018. Our data suggest that WNV-2 entered Italy in 2011 as a result of one or a few penetration events. Clade B differentiated mainly as a result of genetic drift and purifying selection, leading to the appearance of multiple locally circulating sub-clades for different times. Phylodynamic analysis showed a current expansion of the infection among reservoir birds and/or vectors. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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10 pages, 1342 KiB  
Article
Usefulness of Eurasian Magpies (Pica pica) for West Nile virus Surveillance in Non-Endemic and Endemic Situations
by Sebastian Napp, Tomás Montalvo, César Piñol-Baena, Maria Belén Gómez-Martín, Olga Nicolás-Francisco, Mercè Soler and Núria Busquets
Viruses 2019, 11(8), 716; https://0-doi-org.brum.beds.ac.uk/10.3390/v11080716 - 05 Aug 2019
Cited by 15 | Viewed by 3725
Abstract
In September 2017, passive surveillance allowed the detection of West Nile virus (WNV) lineage 2 for the first time in northern Spain in a northern goshawk (Accipiter gentilis). However, a cross sectional study carried out in Eurasian magpies (Pica pica [...] Read more.
In September 2017, passive surveillance allowed the detection of West Nile virus (WNV) lineage 2 for the first time in northern Spain in a northern goshawk (Accipiter gentilis). However, a cross sectional study carried out in Eurasian magpies (Pica pica) in a nearby area evidenced that WNV had been circulating two months earlier. Therefore, active surveillance in Eurasian magpies proved its effectiveness for the early detection of WNV in a non-endemic area. Further surveys in 2018 and the beginning of 2019 using young magpies (i.e., born after 2017) showed the repeated circulation of WNV in the same region in the following transmission season. Therefore, active surveillance in Eurasian magpies as well proved to be useful for the detection of WNV circulation in areas that may be considered as endemic. In this manuscript we present the results of those studies and discuss reasons that make the Eurasian magpies an ideal species for the surveillance of WNV, both in endemic and non-endemic areas. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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25 pages, 2411 KiB  
Article
Evidence for West Nile Virus and Usutu Virus Infections in Wild and Resident Birds in Germany, 2017 and 2018
by Friederike Michel, Michael Sieg, Dominik Fischer, Markus Keller, Martin Eiden, Maximilian Reuschel, Volker Schmidt, Rebekka Schwehn, Monika Rinder, Sylvia Urbaniak, Kerstin Müller, Martina Schmoock, Renke Lühken, Patrick Wysocki, Christine Fast, Michael Lierz, Rüdiger Korbel, Thomas W. Vahlenkamp, Martin H. Groschup and Ute Ziegler
Viruses 2019, 11(7), 674; https://0-doi-org.brum.beds.ac.uk/10.3390/v11070674 - 23 Jul 2019
Cited by 73 | Viewed by 8701
Abstract
Wild birds play an important role as reservoir hosts and vectors for zoonotic arboviruses and foster their spread. Usutu virus (USUV) has been circulating endemically in Germany since 2011, while West Nile virus (WNV) was first diagnosed in several bird species and horses [...] Read more.
Wild birds play an important role as reservoir hosts and vectors for zoonotic arboviruses and foster their spread. Usutu virus (USUV) has been circulating endemically in Germany since 2011, while West Nile virus (WNV) was first diagnosed in several bird species and horses in 2018. In 2017 and 2018, we screened 1709 live wild and zoo birds with real-time polymerase chain reaction and serological assays. Moreover, organ samples from bird carcasses submitted in 2017 were investigated. Overall, 57 blood samples of the live birds (2017 and 2018), and 100 organ samples of dead birds (2017) were positive for USUV-RNA, while no WNV-RNA-positive sample was found. Phylogenetic analysis revealed the first detection of USUV lineage Europe 2 in Germany and the spread of USUV lineages Europe 3 and Africa 3 towards Northern Germany. USUV antibody prevalence rates were high in Eastern Germany in both years. On the contrary, in Northern Germany, high seroprevalence rates were first detected in 2018, with the first emergence of USUV in this region. Interestingly, high WNV-specific neutralizing antibody titers were observed in resident and short-distance migratory birds in Eastern Germany in 2018, indicating the first signs of a local WNV circulation. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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23 pages, 3938 KiB  
Article
Role of NS1 and TLR3 in Pathogenesis and Immunity of WNV
by Sameera Patel, Alessandro Sinigaglia, Luisa Barzon, Matteo Fassan, Florian Sparber, Salome LeibundGut-Landmann and Mathias Ackermann
Viruses 2019, 11(7), 603; https://0-doi-org.brum.beds.ac.uk/10.3390/v11070603 - 03 Jul 2019
Cited by 9 | Viewed by 3226
Abstract
West Nile Virus (WNV) is a mosquito-transmitted flavivirus which causes encephalitis especially in elderly and immunocompromised individuals. Previous studies have suggested the protective role of the Toll-like receptor 3 (TLR3) pathway against WNV entry into the brain, while the WNV non-structural protein 1 [...] Read more.
West Nile Virus (WNV) is a mosquito-transmitted flavivirus which causes encephalitis especially in elderly and immunocompromised individuals. Previous studies have suggested the protective role of the Toll-like receptor 3 (TLR3) pathway against WNV entry into the brain, while the WNV non-structural protein 1 (NS1) interferes with the TLR3 signaling pathway, besides being a component of viral genome replication machinery. In this study, we investigated whether immunization with NS1 could protect against WNV neuroinvasion in the context of TLR3 deficiency. We immunized mice with either an intact or deleted TLR3 system (TLR3KO) with WNV envelope glycoprotein (gE) protein, NS1, or a combination of gE and NS1. Immunization with gE or gE/NS1, but not with NS1 alone, induced WNV neutralizing antibodies and protected against WNV brain invasion and inflammation. The presence of intact TLR3 signaling had no apparent effect on WNV brain invasion. However, mock-immunized TLR3KO mice had higher inflammatory cell invasion upon WNV brain infection than NS1-immunized TLR3KO mice and wild type mice. Thus, immunization against NS1 may reduce brain inflammation in a context of TLR3 signaling deficiency. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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11 pages, 663 KiB  
Article
Culex torrentium: A Potent Vector for the Transmission of West Nile Virus in Central Europe
by Stephanie Jansen, Anna Heitmann, Renke Lühken, Mayke Leggewie, Michelle Helms, Marlis Badusche, Giada Rossini, Jonas Schmidt-Chanasit and Egbert Tannich
Viruses 2019, 11(6), 492; https://0-doi-org.brum.beds.ac.uk/10.3390/v11060492 - 29 May 2019
Cited by 35 | Viewed by 5412
Abstract
The continuous circulation of West Nile virus (WNV) in Central, South and East Europe and its recent detection in several dead birds and two horses in Germany highlights the need for information on WNV vector competence of mosquitoes from Central Europe. Therefore, three [...] Read more.
The continuous circulation of West Nile virus (WNV) in Central, South and East Europe and its recent detection in several dead birds and two horses in Germany highlights the need for information on WNV vector competence of mosquitoes from Central Europe. Therefore, three common Culex species (Culex pipiens biotype pipiens, Culex pipiens biotype molestus and Culex torrentium) from Germany were orally infected with WNV and kept at 18 °C, 21 °C, 24 °C or 27 °C for 14 or 21 days post infection (dpi). Thereafter viable WNV was present in the saliva in all tested taxa, but only at incubation temperatures of 24 °C or 27 °C and predominantly at the extended incubation period of 21 dpi. Highest transmission efficiency rates of 17 % (24 °C) and 24% (27 °C) were found for Cx. torrentium. Culex p. pipiens and Cx. p. molestus showed low transmission efficiencies with a maximum of only 3%. Consequently, temperatures above 21 °C support transmission of WNV, which matches the predominant distribution of human WNV cases around the Mediterranean Sea and in South-East Europe. Culex torrentium has been identified as a potent vector for WNV in Central and Northern Europe, which highlights the need for surveillance of mosquito-borne viruses north of the Alps. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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Review

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17 pages, 564 KiB  
Review
Twenty Years of Progress Toward West Nile Virus Vaccine Development
by Jaclyn A. Kaiser and Alan D.T. Barrett
Viruses 2019, 11(9), 823; https://0-doi-org.brum.beds.ac.uk/10.3390/v11090823 - 05 Sep 2019
Cited by 43 | Viewed by 7475
Abstract
Although West Nile virus (WNV) has been a prominent mosquito-transmitted infection in North America for twenty years, no human vaccine has been licensed. With a cumulative number of 24,714 neurological disease cases and 2314 deaths in the U.S. since 1999, plus a large [...] Read more.
Although West Nile virus (WNV) has been a prominent mosquito-transmitted infection in North America for twenty years, no human vaccine has been licensed. With a cumulative number of 24,714 neurological disease cases and 2314 deaths in the U.S. since 1999, plus a large outbreak in Europe in 2018 involving over 2000 human cases in 15 countries, a vaccine is essential to prevent continued morbidity, mortality, and economic burden. Currently, four veterinary vaccines are licensed, and six vaccines have progressed into clinical trials in humans. All four veterinary vaccines require multiple primary doses and annual boosters, but for a human vaccine to be protective and cost effective in the most vulnerable older age population, it is ideal that the vaccine be strongly immunogenic with only a single dose and without subsequent annual boosters. Of six human vaccine candidates, the two live, attenuated vaccines were the only ones that elicited strong immunity after a single dose. As none of these candidates have yet progressed beyond phase II clinical trials, development of new candidate vaccines and improvement of vaccination strategies remains an important area of research. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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11 pages, 243 KiB  
Review
West Nile Virus Associations in Wild Mammals: An Update
by J. Jeffrey Root and Angela M. Bosco-Lauth
Viruses 2019, 11(5), 459; https://0-doi-org.brum.beds.ac.uk/10.3390/v11050459 - 21 May 2019
Cited by 23 | Viewed by 3926
Abstract
Although West Nile virus (WNV) is generally thought to circulate among mosquitoes and birds, several historic and recent works providing evidence of WNV activity in wild mammals have been published. Indeed, a previous review tabulated evidence of WNV exposure in at least 100 [...] Read more.
Although West Nile virus (WNV) is generally thought to circulate among mosquitoes and birds, several historic and recent works providing evidence of WNV activity in wild mammals have been published. Indeed, a previous review tabulated evidence of WNV exposure in at least 100 mammalian species. Herein, we provide an update on WNV activity in wild and select other mammals that have been reported since the last major review article on this subject was published in early 2013. Of interest, new species, such as Hoffman’s two-toed sloths (Choloepus hoffmanni), are now included in the growing list of wild mammals that have been naturally exposed to WNV. Furthermore, new instances of WNV viremia as well as severe disease presumably caused by this virus have been reported in wild mammals (e.g., the Virginia opossum [Didelphis virginiana]) from natural and semi-captive (e.g., zoological institution) settings. Regrettably, few recent challenge studies have been conducted on wild mammals, which would provide key information as to their potential role(s) in WNV cycles. Largely based on these recent findings, important future lines of research are recommended to assess which mammalian species are commonly exposed to WNV, which mammal species develop viremias sufficient for infecting mosquitoes, and which mammal species might be negatively affected by WNV infection at the species or population level. Full article
(This article belongs to the Special Issue West Nile Virus 2019)

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12 pages, 3441 KiB  
Brief Report
Multi-Approach Investigation Regarding the West Nile Virus Situation in Hungary, 2018
by Brigitta Zana, Károly Erdélyi, Anna Nagy, Eszter Mezei, Orsolya Nagy, Mária Takács, Tamás Bakonyi, Petra Forgách, Orsolya Korbacska-Kutasi, Orsolya Fehér, Péter Malik, Krisztina Ursu, Péter Kertész, Anett Kepner, Máté Martina, Tamás Süli, Zsófia Lanszki, Gábor Endre Tóth, Anett Kuczmog, Balázs Somogyi, Ferenc Jakab and Gábor Kemenesiadd Show full author list remove Hide full author list
Viruses 2020, 12(1), 123; https://0-doi-org.brum.beds.ac.uk/10.3390/v12010123 - 20 Jan 2020
Cited by 11 | Viewed by 6008
Abstract
The West Nile virus is endemic in multiple European countries and responsible for several epidemics throughout the European region. Its evolution into local or even widespread epidemics is driven by multiple factors from genetic diversification of the virus to environmental conditions. The year [...] Read more.
The West Nile virus is endemic in multiple European countries and responsible for several epidemics throughout the European region. Its evolution into local or even widespread epidemics is driven by multiple factors from genetic diversification of the virus to environmental conditions. The year of 2018 was characterized by an extraordinary increase in human and animal cases in the Central-Eastern European region, including Hungary. In a collaborative effort, we summarized and analyzed the genetic and serologic data of WNV infections from multiple Hungarian public health institutions, universities, and private organizations. We compared human and veterinary serologic data, along with NS5 and NS3 gene sequence data through 2018. Wild birds were excellent indicator species for WNV circulation in each year. Our efforts resulted in documenting the presence of multiple phylogenetic subclades with Balkans and Western-European progenitor sequences of WNV circulating among human and animal populations in Hungary prior to and during the 2018 epidemic. Supported by our sequence and phylogenetic data, the epidemic of 2018 was not caused by recently introduced WNV strains. Unfortunately, Hungary has no country-wide integrated surveillance system which would enable the analysis of related conditions and provide a comprehensive epidemiological picture. The One Health approach, involving multiple institutions and experts, should be implemented in order to fully understand ecological background factors driving the evolution of future epidemics. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
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