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Viruses Apr 2022Among emerging arthropod-borne viruses (arbovirus), West Nile virus (WNV) is a flavivirus that can be associated with severe neuroinvasive infections in humans. In 2018,...
Among emerging arthropod-borne viruses (arbovirus), West Nile virus (WNV) is a flavivirus that can be associated with severe neuroinvasive infections in humans. In 2018, the European WNV epidemic resulted in over 2000 cases, representing the most important arboviral epidemic in the European continent. Characterization of inflammation and neuronal biomarkers released during WNV infection, especially in the context of neuronal impairments, could provide insight into the development of predictive tools that could be beneficial for patient outcomes. We first analyzed the inflammatory signature in the serum of WNV-infected mice and found increased concentrations of several inflammatory cytokines. We next analyzed serum and cerebrospinal-fluid (CSF) samples from a cohort of patients infected by WNV between 2018 and 2019 in Hungary to quantify a large panel of inflammatory cytokines and neurological factors. We found higher levels of inflammatory cytokines (e.g., IL4, IL6, and IL10) and neuronal factors (e.g., BDNF, GFAP, MIF, TDP-43) in the sera of WNV-infected patients with neuroinvasive disease. Furthermore, the serum inflammatory profile of these patients persisted for several weeks after initial infection, potentially leading to long-term sequelae and having a deleterious effect on brain neurovasculature. This work suggests that early signs of increased serum concentrations of inflammatory cytokines and neuronal factors could be a signature underlying the development of severe neurological impairments. Biomarkers could play an important role in patient monitoring to improve care and prevent undesirable outcomes.
Topics: Animals; Biomarkers; Cytokines; Humans; Mice; Neuroinflammatory Diseases; West Nile Fever; West Nile virus
PubMed: 35458486
DOI: 10.3390/v14040756 -
Frontiers in Cellular and Infection... 2023In Spain, the largest human West Nile virus (WNV) outbreak among humans was reported in 2020, constituting the second most important outbreak in Europe that season....
In Spain, the largest human West Nile virus (WNV) outbreak among humans was reported in 2020, constituting the second most important outbreak in Europe that season. Extremadura (southwestern Spain) was one of the affected areas, reporting six human cases. The first autochthonous human case in Spain was reported in Extremadura in 2004, and no other human cases were reported until 2020. In this work, we describe the first WNV human outbreak registered in Extremadura, focusing on the most important clinical aspects, diagnostic results, and control actions which followed. In 2020, from September to October, human WNV infections were diagnosed using a combination of molecular and serological methods (an in-house specific qRT-PCR and a commercial ELISA for anti-WNV IgM and IgG antibodies) and by analysing serum, urine, and/or cerebrospinal fluid samples. Serological positive serum samples were further tested using commercial kits against related flaviviruses Usutu and Tick-borne encephalitis in order to analyse serological reactivity and to confirm the results by neutralisation assays. In total, six cases of WNV infection (five with neuroinvasive disease and one with fever) were identified. Clinical presentation and laboratory findings are described. No viral RNA was detected in any of the analysed samples, but serological cross-reactivity was detected against the other tested flaviviruses. Molecular and serological methods for WNV detection in various samples as well as differential diagnosis are recommended. The largest number of human cases of WNV infection ever registered in Extremadura, Spain, occurred in 2020 in areas where circulation of WNV and other flaviviruses has been previously reported in humans and animals. Therefore, it is necessary to enhance surveillance not only for the early detection and implementation of response measures for WNV but also for other emerging flaviviruses that could be endemic in this area.
Topics: Animals; Humans; West Nile virus; West Nile Fever; Spain; Flavivirus; Antibodies, Viral
PubMed: 37469597
DOI: 10.3389/fcimb.2023.1155867 -
Virulence Dec 2021West Nile virus (WNV) is a flavivirus which transmission cycle is maintained between mosquitoes and birds, although it occasionally causes sporadic outbreaks in horses...
West Nile virus (WNV) is a flavivirus which transmission cycle is maintained between mosquitoes and birds, although it occasionally causes sporadic outbreaks in horses and humans that can result in serious diseases and even death. Since its first isolation in Africa in 1937, WNV had been considered a neglected pathogen until its recent spread throughout Europe and the colonization of America, regions where it continues to cause outbreaks with severe neurological consequences in humans and horses. Although our knowledge about the characteristics and consequences of the virus has increased enormously lately, many questions remain to be resolved. Here, we thoroughly update our knowledge of different aspects of the WNV life cycle: virology and molecular classification, host cell interactions, transmission dynamics, host range, epidemiology and surveillance, immune response, clinical presentations, pathogenesis, diagnosis, prophylaxis (antivirals and vaccines), and prevention, and we highlight those aspects that are still unknown and that undoubtedly require further investigation.
Topics: Animals; Culicidae; Europe; Horses; Virulence; West Nile Fever; West Nile virus
PubMed: 33843445
DOI: 10.1080/21505594.2021.1908740 -
Viruses Jul 2022There are at least five common mosquito-borne viruses (MBVs) recorded in Egypt, including dengue virus (DENV), Rift Valley fever virus (RVFV), West Nile virus (WNV),... (Review)
Review
There are at least five common mosquito-borne viruses (MBVs) recorded in Egypt, including dengue virus (DENV), Rift Valley fever virus (RVFV), West Nile virus (WNV), Chikungunya virus, and Sindbis virus. Unexpected outbreaks caused by MBVs reflect the deficiencies of the MBV surveillance system in Egypt. This systematic review characterized the epidemiology of MBV prevalence in Egypt. Human, animal, and vector prevalence studies on MBVs in Egypt were retrieved from Web of Science, PubMed, and Bing Scholar, and 33 eligible studies were included for further analyses. The monophyletic characterization of the RVFV and WNV strains found in Egypt, which spans about half a century, suggests that both RVFV and WNV are widely transmitted in this nation. Moreover, the seropositive rates of DENV and WNV in hosts were on the rise in recent years, and spillover events of DENV and WNV to other countries from Egypt have been recorded. The common drawback for surveillance of MBVs in Egypt is the lack of seroprevalence studies on MBVs, especially in this century. It is necessary to evaluate endemic transmission risk, establish an early warning system for MBVs, and develop a sound joint system for medical care and public health for managing MBVs in Egypt.
Topics: Animals; Culicidae; Egypt; Humans; Rift Valley fever virus; Seroepidemiologic Studies; West Nile Fever; West Nile virus
PubMed: 35891557
DOI: 10.3390/v14071577 -
Journal of Clinical Virology : the... Jun 2020West Nile virus (WNV) lineage 2, and especially the Hungarian clade, predominates in Europe. Most of the Hungarian clade strains cluster into 2 groups:...
BACKGROUND
West Nile virus (WNV) lineage 2, and especially the Hungarian clade, predominates in Europe. Most of the Hungarian clade strains cluster into 2 groups: Central/South-West European and Balkan.
OBJECTIVES
Since there was not any study on WNV in mosquitoes in Bulgaria, the present study was designed to test Culex spp. mosquitoes in areas near the Danube river. The aim of the study was to gain an insight into the recent molecular epidemiology of WNV in Bulgaria.
STUDY DESIGN
A total of 1871 Culex pipiens mosquitoes collected in 2018 and clinical samples from 23 patients with West Nile neuroinavsive disease observed in 2018 and 2019 were tested by TaqMan RT-PCR and RT-nested PCR and PCR products were sequenced.
RESULTS
WNV RNA was detected in clinical samples from 10 patients and in five (12.2 %) of 41 pools of Cx. pipiens mosquitos by realtime RT-PCR, resulting in a minimum infection rate of mosquitoes of 0.27 %. Phylogenetic analysis based on partial NS3 gene sequences from one clinical sample and four mosquito pools showed that all sequences clustered into the Hungarian clade of WNV lineage 2 and all but one were identical to respective sequences from Romania. Whole genome sequences of one mosquito pool belong to the Hungarian group of WNV lineage 2 and cluster in a separate subclade from the Bulgarian strain from 2015, suggesting that at least two different introductions occurred in Bulgaria.
CONCLUSIONS
The current study provides insights into the geographic distribution of WNV in Bulgaria.
Topics: Animals; Bulgaria; Culex; Genome, Viral; Humans; Mosquito Vectors; Phylogeny; West Nile Fever; West Nile virus; Whole Genome Sequencing
PubMed: 32305885
DOI: 10.1016/j.jcv.2020.104365 -
Viruses Jan 2023In 2022, Greece was the second most seriously affected European country in terms of the West Nile virus (WNV), after Italy. Specifically, Central Macedonia was the...
In 2022, Greece was the second most seriously affected European country in terms of the West Nile virus (WNV), after Italy. Specifically, Central Macedonia was the region with the most reported human cases (81.5%). In the present study, 30,816 female Culex pipiens sensu lato mosquitoes were collected from May to September 2022 in the seven regional units of Central Macedonia; they were then grouped into 690 pools and tested for WNV, while next-generation sequencing was applied to the samples, which showed a cycle threshold of Ct < 30 in a real-time RT-PCR test. WNV was detected in 5.9% of pools, with significant differences in the detection rate among regional units and months. It is of interest that in the Thessaloniki regional unit, where most of the human cases were observed, the virus circulation started earlier, peaked earlier, and lasted longer than in the other regional units. All sequences clustered into the Central European subclade of WNV lineage 2, and the virus strain differed from the initial Greek strain of 2010 by 0.52% and 0.27% at the nucleotide and amino acid levels, respectively. Signature substitutions were present, such as S73P and T157A in the prM and E structural proteins, respectively. The screening of mosquitoes provides useful information for virus circulation in a region with a potential for early warning, while the availability of whole-genome sequences is essential for further studies, including virus evolution.
Topics: Animals; Female; Humans; West Nile virus; Culex; Culicidae; Greece; West Nile Fever
PubMed: 36680264
DOI: 10.3390/v15010224 -
Methods in Molecular Biology (Clifton,... 2023The mosquito-borne West Nile virus (WNV) poses a great threat to public health as no vaccine or specific antiviral treatment is available. Exploring virus-host...
The mosquito-borne West Nile virus (WNV) poses a great threat to public health as no vaccine or specific antiviral treatment is available. Exploring virus-host interactions, specifically host factors that are required for virus infection, is important for better understanding the biology, pathogenesis, and transmission of WNV. Such essential host factors may also represent antiviral targets. The development of CRISPR technology has provided a powerful and convenient tool to perturbate host gene expression, allowing for unbiased, genome-wide screens of host factors for virus infection. Here we describe the necessary steps for performing a CRISPR knockout screen, which can also be applied to other viruses, to identify host factors critical for WNV infection.
Topics: Animals; Clustered Regularly Interspaced Short Palindromic Repeats; Host Microbial Interactions; West Nile virus; Antiviral Agents; Technology
PubMed: 36331769
DOI: 10.1007/978-1-0716-2760-0_11 -
Journal of the American Mosquito... Dec 2020Identifying the array of vectors that play a role in perpetuating West Nile virus (WNV) infection in endemic foci will help in controlling the disease. Aedes japonicus...
Identifying the array of vectors that play a role in perpetuating West Nile virus (WNV) infection in endemic foci will help in controlling the disease. Aedes japonicus has the potential to be a vector in the wild of at least 3 kinds of encephalitis, including WNV. Aedes japonicus is a nonnative species in the USA that is temperature tolerant and a potential human biter. Detection of WNV in mosquito pools of this field-collected invasive species, combined with their ability to feed on humans, make this mosquito species a possible public health concern. In this study, we collected mosquito abundance data and tested them for WNV-positive mosquito samples from 3 counties in New York State. We found a significant association between the season and land demography and the likelihood of the virus in Ae. japonicus.
Topics: Aedes; Animals; Female; New York; West Nile virus
PubMed: 33647113
DOI: 10.2987/20-6958.1 -
Current Opinion in Virology Oct 2016Dengue (DENV) and West Nile (WNV) viruses are mosquito-transmitted flaviviruses that cause significant morbidity and mortality worldwide. Disease severity and... (Review)
Review
Dengue (DENV) and West Nile (WNV) viruses are mosquito-transmitted flaviviruses that cause significant morbidity and mortality worldwide. Disease severity and pathogenesis of DENV and WNV infections in humans depend on many factors, including pre-existing immunity, strain virulence, host genetics and virus-host interactions. Among the flavivirus-host interactions, viral evasion of type I interferon (IFN)-mediated innate immunity has a critical role in modulating pathogenesis. DENV and WNV have evolved effective strategies to evade immune surveillance pathways that lead to IFN induction and to block signaling downstream of the IFN-α/β receptor. Here, we discuss recent advances in our understanding of the molecular mechanisms by which DENV and WNV antagonize the type I IFN response in human cells.
Topics: Dengue Virus; Host-Pathogen Interactions; Humans; Immune Evasion; Immunity, Innate; Interferon Type I; West Nile virus
PubMed: 27792906
DOI: 10.1016/j.coviro.2016.09.013 -
The Journal of General Virology Apr 2020The fidelity of flaviviruses is thought to be tightly regulated for optimal fitness within and between hosts. West Nile virus (WNV) high-fidelity (HiFi) mutations V793I...
The fidelity of flaviviruses is thought to be tightly regulated for optimal fitness within and between hosts. West Nile virus (WNV) high-fidelity (HiFi) mutations V793I and G806R within the RNA-dependent RNA polymerase, and low-fidelity (LoFi) mutation T248I within the methyltransferase, were previously shown to attenuate infectivity and replicative fitness in mosquitoes and (CXT) cells but not in mammalian cells. We hypothesized that fidelity alterations would modify adaptation and maintenance in a host-specific manner. To test this hypothesis, wild-type (WT), HiFi (V793I/G806R) and LoFi (T248I) variants were sequentially passaged eight times in avian (PDE) or mosquito cells, or alternately between the two. Initial characterization confirmed that fidelity mutants are attenuated in mosquito, but not avian, cells. Deep sequencing revealed mutations unique to both cell lines and fidelity mutants, including ENV G1378A, a mutation associated with avian cell adaptation. To characterize maintenance and adaptation, viral outputs were monitored throughout passaging and viral fitness was assessed. The results indicate that fidelity mutants can at times recover fitness during mosquito cell passage, but remain attenuated relative to WT. Despite similar initial fitness, LoFi mutants were impaired during sequential passage in avian cells. Conversely, HiFi mutants passaged in avian cells showed increased adaptation, suggesting that increased fidelity may be advantageous in avian hosts. Although some adaptation occurred with individual mutants, the output titres of fidelity mutants were on average lower and were often lost during host switching. These data confirm that arbovirus fidelity is likely fine-tuned to maximize survival in disparate hosts.
Topics: Adaptation, Physiological; Animals; Birds; Cell Line; Computational Biology; Culicidae; Ducks; Host Microbial Interactions; Mutation; Quasispecies; RNA-Dependent RNA Polymerase; Serial Passage; Viral Envelope Proteins; Virus Replication; West Nile virus
PubMed: 32068528
DOI: 10.1099/jgv.0.001393