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MMWR. Morbidity and Mortality Weekly... May 2024
Topics: Humans; United States; West Nile Fever; Arbovirus Infections; Disease Notification; Adult
PubMed: 38814815
DOI: 10.15585/mmwr.mm7321a2 -
Wellcome Open Research 2024is an invasive mosquito species with an extensive and expanding inter-continental distribution, currently reported across Asia, Africa, the Middle East, Europe and now...
BACKGROUND
is an invasive mosquito species with an extensive and expanding inter-continental distribution, currently reported across Asia, Africa, the Middle East, Europe and now Australia. It is an important vector of medical and veterinary pathogens which cause significant morbidity and mortality in human and animal populations. Across regions endemic for Japanese encephalitis virus (JEV), is considered the major vector and has also been shown to contribute to the transmission of several other zoonotic arboviruses including Rift Valley fever virus (RVFV) and West Nile virus (WNV).
METHODS
In this study, we used laboratory vector competence experiments to determine if from a Southern European population were competent JEV vectors. We also obtained samples from multiple geographically dispersed populations from countries within Europe, Africa, Eurasia and Asia to perform phylogenetic analysis to measure the level of mitochondrial divergence using the ( ) gene. We also undertook bacterial gene amplicon sequencing to determine microbial diversity and used multi-locus sequence typing (MLST) to determine any evidence for the presence of strains of the naturally occurring endosymbiotic bacterium .
RESULTS
from a Greek population were shown be be competent vectors of JEV with high levels of virus present in saliva. We found a signficant level of mitochondrial genetic diversity using the mosquito gene between geographically dispersed populations. Furthermore, we report diverse microbiomes identified by gene amplicon sequencing within and between geographical populations. Evidence for the detection of the endosymbiotic bacteria was confirmed using -specific PCR and MLST.
CONCLUSIONS
This study enhances our understanding of the diversity of and the associated microbiome across its inter-continental range and highlights the need for greater surveillance of this invasive vector species in Europe.
PubMed: 38800519
DOI: 10.12688/wellcomeopenres.20761.1 -
IScience Jun 2024Temperature is increasing globally, and vector-borne diseases are particularly responsive to such increases. While it is known that temperature influences mosquito life...
Temperature is increasing globally, and vector-borne diseases are particularly responsive to such increases. While it is known that temperature influences mosquito life history traits, transmission models have not historically considered population-specific effects of temperature. We assessed the interaction between population and temperature in New York State (NYS) and utilized novel empirical data to inform predictive models of West Nile virus (WNV) transmission. Genetically and regionally distinct populations from NYS were reared at various temperatures, and life history traits were monitored and used to inform trait-based models. Variation in life history traits and population-dependent thermal responses account for a predicted 2.9°C difference in peak transmission that is reflected in regional differences in WNV prevalence. We additionally identified genetic signatures that may contribute to distinct thermal responses. Together, these data demonstrate how population variation contributes to significant geographic variability in arbovirus transmission with changing climates.
PubMed: 38799579
DOI: 10.1016/j.isci.2024.109934 -
Frontiers in Immunology 2024Emerging infectious diseases represent a significant threat to global health, with West Nile virus (WNV) being a prominent example due to its potential to cause severe...
Emerging infectious diseases represent a significant threat to global health, with West Nile virus (WNV) being a prominent example due to its potential to cause severe neurological disorders alongside mild feverish conditions. Particularly prevalent in the continental United States, WNV has emerged as a global concern, with outbreaks indicating the urgent need for effective prophylactic measures. The current problem is that the absence of a commercial vaccine against WNV highlights a critical gap in preventive strategies against WNV. This study aims to address this gap by proposing a novel, multivalent vaccine designed using immunoinformatics approaches to elicit comprehensive humoral and cellular immune responses against WNV. The objective of the study is to provide a theoretical framework for experimental scientists to formulate of vaccine against WNV and tackle the current problem by generating an immune response inside the host. The research employs reverse vaccinology and subtractive proteomics methodologies to identify NP_041724.2 polyprotein and YP_009164950.1 truncated flavivirus polyprotein NS1 as the prime antigens. The selection process for epitopes focused on B and T-cell reactivity, antigenicity, water solubility, and non-allergenic properties, prioritizing candidates with the potential for broad immunogenicity and safety. The designed vaccine construct integrates these epitopes, connected via GPGPG linkers, and supplemented with an adjuvant with the help of another linker EAAAK, to enhance immunogenicity. Preliminary computational analyses suggest that the proposed vaccine could achieve near-universal coverage, effectively targeting approximately 99.74% of the global population, with perfect coverage in specific regions such as Sweden and Finland. Molecular docking and immune simulation studies further validate the potential efficacy of the vaccine, indicating strong binding affinity with toll-like receptor 3 (TLR-3) and promising immune response profiles, including significant antibody-mediated and cellular responses. These findings present the vaccine construct as a viable candidate for further development and testing. While the theoretical and computational results are promising, advancing from in-silico predictions to a tangible vaccine requires comprehensive laboratory validation. This next step is essential to confirm the vaccine's efficacy and safety in eliciting an immune response against WNV. Through this study, we propose a novel approach to vaccine development against WNV and contribute to the broader field of immunoinformatics, showcasing the potential to accelerate the design of effective vaccines against emerging viral threats. The journey from hypothesis to practical solution embodies the interdisciplinary collaboration essential for modern infectious disease management and prevention strategies.
Topics: West Nile virus; Immunodominant Epitopes; Humans; Proteome; West Nile Fever; Computational Biology; West Nile Virus Vaccines; Vaccines, Subunit; Vaccine Development; Epitopes, T-Lymphocyte; Epitopes, B-Lymphocyte; Proteomics; Immunoinformatics; Protein Subunit Vaccines
PubMed: 38799422
DOI: 10.3389/fimmu.2024.1395870 -
Vaccines May 2024West Nile virus (WNV) is capable of causing severe neurologic disease in both humans and equines, making it a disease of importance in both human medicine and veterinary... (Review)
Review
West Nile virus (WNV) is capable of causing severe neurologic disease in both humans and equines, making it a disease of importance in both human medicine and veterinary medicine. No targeted treatments exist for WNV infection in either humans or equines. Infection is treated symptomatically through management of symptoms like fever and seizures. As treatment for WNV is purely supportive, the response to WNV has focused primarily on methods of disease prevention. To this end, research efforts have yielded several effective vaccines for equine use as well as numerous conventional mosquito control techniques. Even with the implementation of these techniques, disease caused by WNV remains a concern since no human vaccine exists. Due to the lack of a human vaccine, novel preventative strategies are under active research and development. Of these strategies, some of the most conceptually promising are techniques using genetically modified mosquitoes, addressing the disease at the vector level with minimal ecological side effects. Taken together, the use of combined, synergistic methods, such as physical barriers, transgenic mosquitoes, and immunological targets, will be the best way to prevent WNV disease.
PubMed: 38793736
DOI: 10.3390/vaccines12050485 -
Viruses May 2024Subgenomic flaviviral RNAs (sfRNAs) are small non-coding products of the incomplete degradation of viral genomic RNA. They accumulate during flaviviral infection and...
Subgenomic flaviviral RNAs (sfRNAs) are small non-coding products of the incomplete degradation of viral genomic RNA. They accumulate during flaviviral infection and have been associated with many functional roles inside the host cell. Studies so far have demonstrated that sfRNA plays a crucial role in determining West Nile virus (WNV) pathogenicity. However, its modulatory role on neuronal homeostasis has not been studied in depth. In this study, we investigated the mechanism of sfRNA biosynthesis and its importance for WNV replication in neuronal cells. We found that sfRNA1 is functionally redundant for both replication and translation of WNV. However, the concurrent absence of sfRNA1 and sfRNA2 species is detrimental for the survival of the virus. Differential expression analysis on RNA-seq data from WT and ΔsfRNA replicon cell lines revealed transcriptional changes induced by sfRNA and identified a number of putative targets. Overall, it was shown that sfRNA contributes to the viral evasion by suppressing the interferon-mediated antiviral response. An additional differential expression analysis among replicon and control Neuro2A cells also clarified the transcriptional changes that support WNV replication in neuronal cells. Increased levels of translation and oxidative phosphorylation, post-translational modification processes, and activated DNA repair pathways were observed in replicon cell lines, while developmental processes such as axonal growth were deficient.
Topics: West Nile virus; RNA, Viral; Virus Replication; Neurons; Animals; Cell Line; Genome, Viral; West Nile Fever; Humans; Mice; Gene Expression Regulation, Viral
PubMed: 38793693
DOI: 10.3390/v16050812 -
Viruses May 2024The West Nile Virus (WNV), a member of the family , is an emerging mosquito-borne flavivirus causing potentially severe infections in humans and animals involving the... (Comparative Study)
Comparative Study
The West Nile Virus (WNV), a member of the family , is an emerging mosquito-borne flavivirus causing potentially severe infections in humans and animals involving the central nervous system (CNS). Due to its emerging tendency, WNV now occurs in many areas where other flaviviruses are co-occurring. Cross-reactive antibodies with flavivirus infections or vaccination (e.g., tick-borne encephalitis virus (TBEV), Usutu virus (USUV), yellow fever virus (YFV), dengue virus (DENV), Japanese encephalitis virus (JEV)) therefore remain a major challenge in diagnosing flavivirus infections. Virus neutralization tests are considered as reference tests for the detection of specific flavivirus antibodies, but are elaborate, time-consuming and need biosafety level 3 facilities. A simple and straightforward assay for the differentiation and detection of specific WNV IgG antibodies for the routine laboratory is urgently needed. In this study, we compared two commercially available enzyme-linked immunosorbent assays (anti-IgG WNV ELISA and anti-NS1-IgG WNV), a commercially available indirect immunofluorescence assay, and a newly developed in-house ELISA for the detection of WNV-NS1-IgG antibodies. All four tests were compared to an in-house NT to determine both the sensitivity and specificity of the four test systems. None of the assays could match the specificity of the NT, although the two NS1-IgG based ELISAs were very close to the specificity of the NT at 97.3% and 94.6%. The in-house WNV-NS1-IgG ELISA had the best performance regarding sensitivity and specificity. The specificities of the ELISA assays and the indirect immunofluorescence assays could not meet the necessary specificity and/or sensitivity.
Topics: West Nile virus; Antibodies, Viral; Humans; West Nile Fever; Sensitivity and Specificity; Enzyme-Linked Immunosorbent Assay; Serologic Tests; Immunoglobulin G; Fluorescent Antibody Technique, Indirect; Cross Reactions; Animals
PubMed: 38793670
DOI: 10.3390/v16050788 -
Viruses May 2024Humans and equines are two dead-end hosts of the mosquito-borne West Nile virus (WNV) with similar susceptibility and pathogenesis. Since the introduction of WNV... (Review)
Review
Humans and equines are two dead-end hosts of the mosquito-borne West Nile virus (WNV) with similar susceptibility and pathogenesis. Since the introduction of WNV vaccines into equine populations of the United States of America (USA) in late 2002, there have been only sporadic cases of WNV infection in equines. These cases are generally attributed to unvaccinated and under-vaccinated equines. In contrast, due to the lack of a human WNV vaccine, WNV cases in humans have remained steadily high. An average of 115 deaths have been reported per year in the USA since the first reported case in 1999. Therefore, the characterization of protective immune responses to WNV and the identification of immune correlates of protection in vaccinated equines will provide new fundamental information about the successful development and evaluation of WNV vaccines in humans. This review discusses the comparative epidemiology, transmission, susceptibility to infection and disease, clinical manifestation and pathogenesis, and immune responses of WNV in humans and equines. Furthermore, prophylactic and therapeutic strategies that are currently available and under development are described. In addition, the successful vaccination of equines against WNV and the potential lessons for human vaccine development are discussed.
Topics: West Nile Fever; Horses; Animals; West Nile virus; Humans; Horse Diseases; West Nile Virus Vaccines; Vaccination; One Health; United States
PubMed: 38793662
DOI: 10.3390/v16050781 -
Viruses Apr 2024West Nile virus (WNV) is an arbovirus spread primarily by mosquitoes, with humans being a dead-end host. WNV was introduced to Florida in 2001, with 467 confirmed cases...
West Nile virus (WNV) is an arbovirus spread primarily by mosquitoes, with humans being a dead-end host. WNV was introduced to Florida in 2001, with 467 confirmed cases since. It is estimated that 80 percent of cases are asymptomatic, with mild cases presenting as a non-specific flu-like illness. Currently, detection of WNV in humans occurs primarily in healthcare settings via RT-PCR or CSF IgM when patients present with severe manifestations of disease including fever, meningitis, encephalitis, or acute flaccid paralysis. Given the short window of detectable viremia and requirement for CSF sampling, most WNV infections never receive an official diagnosis. This study utilized enzyme-linked immunosorbent assay (ELISA) to detect WNV IgG antibodies in 250 patient serum and plasma samples collected at Tampa General Hospital during 2020 and 2021. Plaque reduction neutralization tests were used to confirm ELISA results. Out of the 250 patients included in this study, 18.8% of them were IgG positive, consistent with previous WNV exposure. There was no relationship between WNV exposure and age or sex.
Topics: Humans; West Nile virus; West Nile Fever; Florida; Male; Female; Antibodies, Viral; Middle Aged; Seroepidemiologic Studies; Immunoglobulin G; Adult; Aged; Young Adult; Adolescent; Aged, 80 and over; Enzyme-Linked Immunosorbent Assay; Hospitalization; Immunoglobulin M
PubMed: 38793601
DOI: 10.3390/v16050719 -
Viruses Apr 2024Genetic studies preceded by the observation of an unknown mosquito species in Mikołów (Poland) confirmed that it belongs to a new invasive species in Polish fauna,... (Review)
Review
Genetic studies preceded by the observation of an unknown mosquito species in Mikołów (Poland) confirmed that it belongs to a new invasive species in Polish fauna, (Theobald, 1901), a known vector for numerous infectious diseases. is expanding its geographical presence, raising concerns about potential disease transmission given its vector competence for chikungunya virus, dengue virus, West Nile virus, and Zika virus. This first genetically confirmed identification of in Poland initiates a comprehensive review of the literature on , its biology and ecology, and the viral infections transmitted by this species. This paper also presents the circumstances of the observation of in Poland and a methodology for identifying this species.
Topics: Poland; Aedes; Animals; Mosquito Vectors; Introduced Species; Humans; West Nile virus; Dengue Virus; Zika Virus; Chikungunya virus
PubMed: 38793584
DOI: 10.3390/v16050703