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PLoS Neglected Tropical Diseases Jun 2024Usutu virus (USUV) is a zoonotic arbovirus infecting mainly wild birds. It is transmitted by ornithophilic mosquitoes, mainly of the genus Culex from birds to birds and...
Usutu virus (USUV) is a zoonotic arbovirus infecting mainly wild birds. It is transmitted by ornithophilic mosquitoes, mainly of the genus Culex from birds to birds and to several vertebrate dead-end hosts. Several USUV lineages, differing in their virulence have emerged in the last decade and now co-circulate in Europe, impacting human populations. However, their relative transmission and effects on their mosquito vectors is still not known. We thus compared the vector competence and survival of Culex pipiens mosquitoes experimentally infected with two distinct USUV lineages, EU2 and EU3, that are known to differ in their virulence and replication in vertebrate hosts. Infection rate was variable among blood feeding assays but variations between EU2 and EU3 lineages were consistent suggesting that Culex pipiens was equally susceptible to infection by both lineages. However, EU3 viral load increased with viral titer in the blood meal while EU2 viral load was high at all titers which suggest a greater replication of EU2 than EU3 in mosquito. While their relative transmission efficiencies are similar, at least at low blood meal titer, positive correlation between transmission and blood meal titer was observed for EU3 only. Contrary to published results in vertebrates, EU3 induced a higher mortality to mosquitoes (i.e. virulence) than EU2 whatever the blood meal titer. Therefore, we found evidence of lineage-specific differences in vectorial capacity and virulence to both the vector and vertebrate host which lead to balanced propagation of both viral lineages. These results highlight the need to decipher the interactions between vectors, vertebrate hosts, and the diversity of arbovirus lineages to fully understand transmission dynamics.
PubMed: 38935783
DOI: 10.1371/journal.pntd.0012295 -
Nature Communications Jun 2024Potential G-quadruplex sites have been identified in the genomes of DNA and RNA viruses and proposed as regulatory elements. The genus Orthoflavivirus contains...
Potential G-quadruplex sites have been identified in the genomes of DNA and RNA viruses and proposed as regulatory elements. The genus Orthoflavivirus contains arthropod-transmitted, positive-sense, single-stranded RNA viruses that cause significant human disease globally. Computational studies have identified multiple potential G-quadruplex sites that are conserved across members of this genus. Subsequent biophysical studies established that some G-quadruplexes predicted in Zika and tickborne encephalitis virus genomes can form and known quadruplex binders reduced viral yields from cells infected with these viruses. The susceptibility of RNA to degradation and the variability of loop regions have made structure determination challenging. Despite these difficulties, we report a high-resolution structure of the NS5-B quadruplex from the West Nile virus genome. Analysis reveals two stacked tetrads that are further stabilized by a stacked triad and transient noncanonical base pairing. This structure expands the landscape of solved RNA quadruplex structures and demonstrates the diversity and complexity of biological quadruplexes. We anticipate that the availability of this structure will assist in solving further viral RNA quadruplexes and provides a model for a conserved antiviral target in Orthoflavivirus genomes.
Topics: G-Quadruplexes; Genome, Viral; RNA, Viral; West Nile virus; Nucleic Acid Conformation; Models, Molecular; Humans; Base Pairing
PubMed: 38926367
DOI: 10.1038/s41467-024-49761-5 -
Veterinary Sciences Jun 2024West Nile virus (WNV) is a re-emerging flavivirus, primarily circulating among avian hosts and mosquito vectors, causing periodic outbreaks in humans and horses, often...
West Nile virus (WNV) is a re-emerging flavivirus, primarily circulating among avian hosts and mosquito vectors, causing periodic outbreaks in humans and horses, often leading to neuroinvasive disease and mortality. Spain has reported several outbreaks, most notably in 2020 with seventy-seven human cases and eight fatalities. WNV has been serologically detected in horses in the Community of Madrid, but to our knowledge, it has never been reported from wild birds in this region. To estimate the seroprevalence of WNV in wild birds and horses in the Community of Madrid, 159 wild birds at a wildlife rescue center and 25 privately owned equines were sampled. Serum from thirteen birds (8.2%) and one equine (4.0%) tested positive with a WNV competitive enzyme-linked immunosorbent assay (cELISA) designed for WNV antibody detection but sensitive to cross-reacting antibodies to other flaviviruses. Virus-neutralization test (VNT) confirmed WNV antibodies in four bird samples (2.5%), and antibodies to undetermined flavivirus in four additional samples. One equine sample (4.0%) tested positive for WNV by VNT, although this horse previously resided in a WN-endemic area. ELISA-positive birds included both migratory and resident species, juveniles and adults. Two seropositive juvenile birds suggest local flavivirus transmission within the Community of Madrid, while WNV seropositive adult birds may have been infected outside Madrid. The potential circulation of flaviviruses, including WNV, in birds in the Madrid Community raises concerns, although further surveillance of mosquitoes, wild birds, and horses in Madrid is necessary to establish the extent of transmission and the principal species involved.
PubMed: 38922006
DOI: 10.3390/vetsci11060259 -
Insects Jun 2024The arbovirus West Nile virus (WNV) is a danger to global health. Spread primarily by mosquitoes, WNV causes about 2000 cases per year in the United States. The natural...
The arbovirus West Nile virus (WNV) is a danger to global health. Spread primarily by mosquitoes, WNV causes about 2000 cases per year in the United States. The natural mosquito immune response controls viral replication so that the host survives but can still transmit the virus. Using the genetically malleable model, we previously dissected innate immune pathways used to control WNV infection. Specifically, we showed that insulin/IGF-1 signaling (IIS) activates a JAK/STAT-mediated immune response that reduces WNV. However, how factors that regulate IIS in insects control infection has not been identified. () encodes a peptide hormone that suppresses insulin secretion. Its mammalian ortholog, Neuromedin U (NMU), is a peptide that regulates the production and secretion of insulin from pancreatic beta cells. In this study, we used and human cell culture models to investigate the roles of these insulin regulators in immune signaling. We found that mutants, which have elevated insulin-like peptide expression, are less susceptible to WNV infection. Increased levels of insulin-like peptides in these flies result in upregulated JAK/STAT activity, leading to protection from infection. Treatment of human cells with the insulin regulator NMU results in increased WNV replication. Further investigation of methods to target Lst in mosquitoes or NMU in mammals can improve vector control methods and may lead to improved therapeutics for human and animal infection.
PubMed: 38921161
DOI: 10.3390/insects15060446 -
Emerging Infectious Diseases Jul 2024We analyzed West Nile Virus (WNV) exposure from 1,222 blood donors during 2017-2018 from an area of south-central Spain. Results revealed WNV seroprevalence of 0.08%...
We analyzed West Nile Virus (WNV) exposure from 1,222 blood donors during 2017-2018 from an area of south-central Spain. Results revealed WNV seroprevalence of 0.08% (95% CI 0.004%-0.4%) in this population. Our findings underscore the need for continued surveillance and research to manage WNV infection in this region.
Topics: Humans; Spain; Blood Donors; West Nile Fever; West Nile virus; Seroepidemiologic Studies; Male; Female; Adult; Middle Aged; Antibodies, Viral; Young Adult; Adolescent; Aged
PubMed: 38916587
DOI: 10.3201/eid3007.240450 -
PLoS Neglected Tropical Diseases Jun 2024West Nile virus (WNV) is the most common mosquito-borne disease in the United States, resulting in hundreds of reported cases yearly in California alone. The...
Exploring the role of temperature and other environmental factors in West Nile virus incidence and prediction in California counties from 2017-2022 using a zero-inflated model.
West Nile virus (WNV) is the most common mosquito-borne disease in the United States, resulting in hundreds of reported cases yearly in California alone. The transmission cycle occurs mostly in birds and mosquitoes, making meteorological conditions, such as temperature, especially important to transmission characteristics. Given that future increases in temperature are all but inevitable due to worldwide climate change, determining associations between temperature and WNV incidence in humans, as well as making predictions on future cases, are important to public health agencies in California. Using surveillance data from the California Department of Public Health (CDPH), meteorological data from the National Oceanic and Atmospheric Administration (NOAA), and vector and host data from VectorSurv, we created GEE autoregressive and zero-inflated regression models to determine the role of temperature and other environmental factors in WNV incidence and predictions. An increase in temperature was found to be associated with an increase in incidence in 11 high-burden Californian counties between 2017-2022 (IRR = 1.06), holding location, time of year, and rainfall constant. A hypothetical increase of two degrees Fahrenheit-predicted for California by 2040-would have resulted in upwards of 20 excess cases per year during our study period. Using 2017-2021 as a training set, meteorological and host/vector data were able to closely predict 2022 incidence, though the models did overestimate the peak number of cases. The zero-inflated model closely predicted the low number of cases in winter months but performed worse than the GEE model during high-transmission periods. These findings suggests that climate change will, and may be already, altering transmission dynamics and incidence of WNV in California, and provides tools to help predict incidence into the future.
PubMed: 38913741
DOI: 10.1371/journal.pntd.0012051 -
MSphere Jun 2024The microbiome plays vital roles in the life history of mosquitoes, including their development, immunity, longevity, and vector competence. Recent advances in...
UNLABELLED
The microbiome plays vital roles in the life history of mosquitoes, including their development, immunity, longevity, and vector competence. Recent advances in sequencing technologies have allowed for detailed exploration into the diverse microorganisms harbored by these medically important insects. Although these meta-studies have cataloged the microbiomes of mosquitoes in several continents, much of the information currently available for North America is limited to the state of California. In this study, we collected >35,000 mosquitoes throughout Manitoba, Canada, over a 3-year period and then harnessed RNA sequencing and targeted reverse transcriptase-PCR to characterize the microbiomes of the eight most pervasive and important vector and pest species. The consensus microbiome of each species was overwhelmingly composed of viruses but also included fungi, bacteria, protozoa, and parasitic invertebrates. The microbial assemblages were heterogeneous between species, even within the same genus. We detected notable pathogens, including the causal agents of Cache Valley Fever, avian malaria, and canine heartworm. The remaining microbiome consisted largely of putatively insect-specific viruses that are not well characterized, including 17 newly discovered viruses from 10 different families. Future research should focus on evaluating the potential application of these viruses in biocontrol, as biomarkers, and/or in disrupting mosquito vectorial capacity. Interestingly, we also detected viruses that naturally infect honeybees and thrips, which were presumably acquired indirectly through nectar foraging behaviors. Overall, we provide the first comprehensive catalog of the microorganisms harbored by the most common and important mosquito vectors and pests in the Canadian Prairies.
IMPORTANCE
Mosquitoes are the most dangerous animals on the planet, responsible for over 800,000 deaths per year globally. This is because they carry and transmit a plethora of human disease-causing microorganisms, such as West Nile virus and the malaria parasite. Recent innovations in nucleic acid sequencing technologies have enabled researchers unparalleled opportunities to characterize the suite of microorganisms harbored by different mosquito species, including the causal agents of disease. In our study, we carried out 3 years of intensive mosquito surveillance in Canada. We collected and characterized the microorganisms harbored by >35,000 mosquitoes, including the identification of the agents of Cache Valley fever, avian malaria, and canine heartworm. We also detected insect-specific viruses and discovered 17 new viruses that have never been reported. This study, which is the first of its kind in Canada and one of only a handful globally, will greatly aid in future infectious disease research.
PubMed: 38912793
DOI: 10.1128/msphere.00203-24 -
GeoHealth Jun 2024Many infectious disease forecasting models in the United States (US) are built with data partitioned into geopolitical regions centered on human activity as opposed to...
Many infectious disease forecasting models in the United States (US) are built with data partitioned into geopolitical regions centered on human activity as opposed to regions defined by natural ecosystems; although useful for data collection and intervention, this has the potential to mask biological relationships between the environment and disease. We explored this concept by analyzing the correlations between climate and West Nile virus (WNV) case data aggregated to geopolitical and ecological regions. We compared correlations between minimum, maximum, and mean annual temperature; precipitation; and annual WNV neuroinvasive disease (WNND) case data from 2005 to 2019 when partitioned into (a) climate regions defined by the National Oceanic and Atmospheric Administration (NOAA) and (b) Level I ecoregions defined by the Environmental Protection Agency (EPA). We found that correlations between climate and WNND in NOAA climate regions and EPA ecoregions were often contradictory in both direction and magnitude, with EPA ecoregions more often supporting previously established biological hypotheses and environmental dynamics underlying vector-borne disease transmission. Using ecological regions to examine the relationships between climate and disease cases can enhance the predictive power of forecasts at various scales, motivating a conceptual shift in large-scale analyses from geopolitical frameworks to more ecologically meaningful regions.
PubMed: 38912225
DOI: 10.1029/2024GH001024 -
Frontiers in Veterinary Science 2024Domestic species, including equids, were introduced in the Galapagos Islands in the XIX century. Equine vector-borne diseases are circulating in South America but their...
Domestic species, including equids, were introduced in the Galapagos Islands in the XIX century. Equine vector-borne diseases are circulating in South America but their occurrence in the Galapagos Island was unknown. The objective of this study was to detect the occurrence of West Nile virus (WNV), Usutu virus (USUV) and equine infectious anemia virus (EIAV) in the four Galapagos Islands raising equids if they were present at a prevalence >1%. Serum samples were collected from 411 equids belonging to 124 owners from April to July 2019. All the results were negative to the ELISA tests used suggesting that WNV, USUV and EIAV are not circulating in the equine population of the Galapagos Islands.
PubMed: 38911677
DOI: 10.3389/fvets.2024.1411624 -
Antiviral Research Jun 2024The flavivirus genus includes human pathogenic viruses such as Dengue (DENV), West Nile (WNV) and Zika virus (ZIKV) posing a global health threat due to limited...
The flavivirus genus includes human pathogenic viruses such as Dengue (DENV), West Nile (WNV) and Zika virus (ZIKV) posing a global health threat due to limited treatment options. Ion channels are crucial for various viral life cycle stages, but their potential as targets for antivirals is often not fully realized due to the lack of selective modulators. Here, we observe that treatment with ML2-SA1, an agonist for the human endolysosomal cation channel TRPML2, impairs ZIKV replication. Upon ML2-SA1 treatment, levels of intracellular genomes and number of released virus particles of two different ZIKV isolates were significantly reduced and cells displayed enlarged vesicular structures and multivesicular bodies with ZIKV envelope protein accumulation. However, no increased ZIKV degradation in lysosomal compartments was observed. Rather, the antiviral effect of ML2-SA1 seemed to manifest by the compound's negative impact on genome replication. Moreover, ML2-SA1 treatment also led to intracellular cholesterol accumulation. ZIKV and many other viruses including the Orthohepevirus Hepatitis E virus (HEV) rely on the endolysosomal system and are affected by intracellular cholesterol levels to complete their life cycle. Since we observed that ML2-SA1 also negatively impacted HEV infections in vitro, this compound may harbor a broader antiviral potential through perturbing the intracellular cholesterol distribution. Besides indicating that TRPML2 may be a promising target for combatting viral infections, we uncover a tentative connection between this protein and cholesterol distribution within the context of infectious diseases.
PubMed: 38901736
DOI: 10.1016/j.antiviral.2024.105940