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Journal of Virology Oct 2023Arboviruses, particularly those transmitted by mosquitoes, pose a significant threat to humans and are an increasing concern because of climate change, human activity,...
Arboviruses, particularly those transmitted by mosquitoes, pose a significant threat to humans and are an increasing concern because of climate change, human activity, and expanding vector-competent populations. West Nile virus is of significant concern as the most frequent mosquito-borne disease transmitted annually within the continental United States. Here, we identify a previously uncharacterized signaling pathway that impacts West Nile virus infection, namely endothelin signaling. Additionally, we demonstrate that we can successfully translate results obtained from into the more relevant human system. Our results add to the growing field of insulin-mediated antiviral immunity and identify potential biomarkers or intervention targets to better address West Nile virus infection and severe disease.
Topics: Animals; Humans; Drosophila melanogaster; Insulin; Signal Transduction; West Nile Fever; West Nile virus; Endothelins
PubMed: 37796127
DOI: 10.1128/jvi.01112-23 -
Journal of Virology Jan 2016The arthropod-borne West Nile virus (WNV) emerged in New York State in 1999 and quickly spread throughout the United States. Transmission is maintained in an enzootic...
UNLABELLED
The arthropod-borne West Nile virus (WNV) emerged in New York State in 1999 and quickly spread throughout the United States. Transmission is maintained in an enzootic cycle in which infected mosquitoes transmit the virus to susceptible hosts during probing and feeding. Arthropod-derived components within the viral inoculum are increasingly acknowledged to play a role in infection of vertebrate hosts. We previously showed that Culex tarsalis mosquito saliva and salivary gland extract (SGE) enhance the in vivo replication of WNV. Here, we characterized the effective dose, timing, and proximity of saliva and SGE administration necessary for enhancement of WNV viremia using a mouse model. Mosquito saliva and SGE enhanced viremia in a dose-dependent manner, and a single mosquito bite or as little as 0.01 μg of SGE was effective at enhancing viremia, suggesting a potent active salivary factor. Viremia was enhanced when SGE was injected in the same location as virus inoculation from 24 h before virus inoculation through 12 h after virus inoculation. These results were confirmed with mosquito saliva deposited by uninfected mosquitoes. When salivary treatment and virus inoculation were spatially separated, viremia was not enhanced. In summary, the effects of mosquito saliva and SGE were potent, long lasting, and localized, and these studies have implications for virus transmission in nature, where vertebrate hosts are fed upon by both infected and uninfected mosquitoes over time. Furthermore, our model provides a robust system to identify the salivary factor(s) responsible for enhancement of WNV replication.
IMPORTANCE
Mosquito-borne viruses are a significant class of agents causing emerging infectious diseases. WNV has caused over 18,000 cases of neuroinvasive disease in the United States since its emergence. We have shown that Culex tarsalis mosquito saliva and SGE enhance the replication of WNV. We now demonstrate that saliva and SGE have potent, long-lasting, and localized effects. Our model provides a robust system to identify the salivary factor(s) and characterize the mechanism responsible for enhancement of WNV replication. These studies could lead to the identification of novel prophylactic or treatment options useful in limiting the spread of WNV, other mosquito-borne viruses, and the diseases that they cause.
Topics: Animals; Culex; Disease Models, Animal; Female; Mice, Inbred C57BL; Saliva; Tissue Extracts; Viral Load; Viremia; West Nile Fever; West Nile virus
PubMed: 26468544
DOI: 10.1128/JVI.02280-15 -
Vaccine Nov 2019Although West Nile virus (WNV) causes annual cases of neurological disease and deaths in humans, a vaccine has not been licensed for human use. Several WNV genes have...
Although West Nile virus (WNV) causes annual cases of neurological disease and deaths in humans, a vaccine has not been licensed for human use. Several WNV genes have been targeted for mutagenesis in attempts to generate live attenuated vaccine candidates, including the non-structural protein NS5. Specifically, mutation of WNV NS5-K61A or NS5-E218A in the catalytic tetrad of the methyltransferase decreases enzyme activity of the NS5 protein and correspondingly attenuates the virus in mice. In this report, NS5-K61A, NS5-E218A, and a double mutant encoding both mutations (NS5-K61A/E218A) were compared both in vitro and in vivo. Each single mutant was strongly attenuated in highly susceptible outbred mice, whereas the double mutant unexpectedly was not attenuated. Sequencing analysis demonstrated that the double mutant was capable of reversion at both residues NS5-61 and NS5-218, whereas the genotype of the single mutants did not show evidence of reversion. Overall, either NS5-K61A or NS5-E218A methyltransferase mutations could be potential mutations to include in a candidate live WNV vaccine; however, multiple mutations in the catalytic tetrad of the methyltransferase are not tolerated.
Topics: Animals; Cell Line; Cytokines; Female; Genotype; Humans; Mice; Models, Molecular; Mutation; Protein Conformation; Structure-Activity Relationship; Viral Nonstructural Proteins; West Nile Fever; West Nile virus
PubMed: 31611100
DOI: 10.1016/j.vaccine.2019.09.045 -
Viruses Mar 2019Bats are known to harbor and transmit many emerging and re-emerging viruses, many of which are extremely pathogenic in humans but do not cause overt pathology in their... (Review)
Review
Bats are known to harbor and transmit many emerging and re-emerging viruses, many of which are extremely pathogenic in humans but do not cause overt pathology in their bat reservoir hosts: henipaviruses (Nipah and Hendra), filoviruses (Ebola and Marburg), and coronaviruses (SARS-CoV and MERS-CoV). Direct transmission cycles are often implicated in these outbreaks, with virus shed in bat feces, urine, and saliva. An additional mode of virus transmission between bats and humans requiring further exploration is the spread of disease via arthropod vectors. Despite the shared ecological niches that bats fill with many hematophagous arthropods (e.g. mosquitoes, ticks, biting midges, etc.) known to play a role in the transmission of medically important arboviruses, knowledge surrounding the potential for bats to act as reservoirs for arboviruses is limited. To this end, a comprehensive literature review was undertaken examining the current understanding and potential for bats to act as reservoirs for viruses transmitted by blood-feeding arthropods. Serosurveillance and viral isolation from either free-ranging or captive bats are described in relation to four arboviral groups (, , , ). Further, ecological associations between bats and hematophagous viral vectors are characterized (e.g. bat bloodmeals in mosquitoes, ingestion of mosquitoes by bats, etc). Lastly, knowledge gaps related to hematophagous ectoparasites (bat bugs and bed bugs () and bat flies ( and )), in addition to future directions for characterization of bat-vector-virus relationships are described.
Topics: Animals; Arboviruses; Arthropod Vectors; Chiroptera; Dengue Virus; Diptera; Disease Reservoirs; Mosquito Vectors; West Nile virus; Zika Virus; Zoonoses
PubMed: 30832426
DOI: 10.3390/v11030215 -
Parasites & Vectors May 2021West Nile (WNV) and Usutu (USUV) are emerging vector-borne zoonotic flaviviruses. They are antigenically very similar, sharing the same life cycle with birds as...
BACKGROUND
West Nile (WNV) and Usutu (USUV) are emerging vector-borne zoonotic flaviviruses. They are antigenically very similar, sharing the same life cycle with birds as amplification host, Culicidae as vector, and man/horse as dead-end host. They can co-circulate in an overlapping geographic range. In Europe, surveillance plans annually detect several outbreaks.
METHODS
In Italy, a WNV/USUV surveillance plan is in place through passive and active surveillance. After a 2018 WNV outbreak, a reinforced integrated risk-based surveillance was performed in four municipalities through clinical and serological surveillance in horses, Culicidae catches, and testing on human blood-based products for transfusion.
RESULTS
Eight WNV cases in eight equine holdings were detected. Twenty-three mosquitoe catches were performed and 2367 specimens of Culex pipiens caught; 17 pools were USUV positive. A total of 8889 human blood donations were tested, and two asymptomatic donors were USUV positive.
CONCLUSIONS
Different surveillance components simultaneously detected WNV only in horses and USUV only in humans and mosquitoes. While in endemic areas (i.e. northern Italy) entomological surveillance is successfully used as an early detection warning, this method in central Italy seems ineffective. To achieve a high level of sensitivity, the entomological trapping effort should probably exceed a reasonable balance between cost and performance. Besides, WNV/USUV early detection can be addressed by horses and birds. Further research is needed to adapt the surveillance components in different epidemiological contexts.
Topics: Animals; Culex; Epidemiological Monitoring; Flavivirus; Flavivirus Infections; Horse Diseases; Horses; Humans; Italy; Mosquito Vectors; West Nile Fever; West Nile virus
PubMed: 33962673
DOI: 10.1186/s13071-021-04736-z -
Brazilian Journal of Microbiology :... Jun 2021Flaviviruses as West Nile virus (WNV), Saint Louis encephalitis virus (SLEV), Ilhéus virus (ILHV), and Rocio virus (ROCV) are previously reported in different Brazilian...
Flaviviruses as West Nile virus (WNV), Saint Louis encephalitis virus (SLEV), Ilhéus virus (ILHV), and Rocio virus (ROCV) are previously reported in different Brazilian regions, but studies in Southern Brazil are still scarce. To improve the information regarding flaviviruses in Southern Brazil, horse serum samples were analyzed using RT-qPCR and a commercial ELISA-Ab against WNV followed by PRNT. All 1000 samples analyzed by real-time RT-PCR resulted negative. The 465 subsampled samples were analyzed by a commercial ELISA-Ab against WNV, and the 18.5% (86/465) positive samples were further analyzed by PRNT. In the PRNT, 13/86 and 2/86 horses were positive for SLEV and WNV, respectively. It was observed that 5.8% (13/226) of the farms presented at least one positive animal for SLEV in PRNT, whereas 0.9% (2/226) for WNV. Apart from the lower seroprevalences identified when compared to data previously reported in other Brazilian regions, our results suggest that public health professionals must be aware of the presence of these potential zoonotic pathogens.
Topics: Animals; Antibodies, Viral; Brazil; Encephalitis Virus, St. Louis; Encephalitis, Arbovirus; Flavivirus Infections; Geography; Horse Diseases; Horses; RNA, Viral; Seroepidemiologic Studies; West Nile virus
PubMed: 33797731
DOI: 10.1007/s42770-021-00474-7 -
Viruses Jul 2019Monitoring West Nile virus (WNV) and Usutu virus (USUV) activity now has the highest priority among mosquito-borne pathogenic viruses circulating in the European Union....
Monitoring West Nile virus (WNV) and Usutu virus (USUV) activity now has the highest priority among mosquito-borne pathogenic viruses circulating in the European Union. This study documents a first time detection and the co-circulation of WNV lineage-2 (with the minimal prevalence of 0.46%) and USUV clade Europe 2 (with the minimal prevalence of 0.25%) in mosquitoes from the same habitat of south-western Slovakia and underlines necessity to perform rigorous surveillance in birds, mosquitoes, horses and humans in that country.
Topics: Animals; Birds; Culex; Culicidae; Ecosystem; Female; Flavivirus; Flavivirus Infections; Horses; Humans; Mosquito Vectors; Phylogeny; Prevalence; Public Health; Slovakia; West Nile Fever; West Nile virus
PubMed: 31336825
DOI: 10.3390/v11070639 -
Emerging Infectious Diseases Dec 2018Host migration and emerging pathogens are strongly associated, especially with regard to zoonotic diseases. West Nile virus (WNV), a mosquitoborne pathogen capable of...
Host migration and emerging pathogens are strongly associated, especially with regard to zoonotic diseases. West Nile virus (WNV), a mosquitoborne pathogen capable of causing severe, sometimes fatal, neuroinvasive disease in humans, is maintained in highly mobile avian hosts. Using phylogeographic approaches, we investigated the relationship between WNV circulation in the United States and the flight paths of terrestrial birds. We demonstrated southward migration of WNV in the eastern flyway and northward migration in the central flyway, which is consistent with the looped flight paths of many terrestrial birds. We also identified 3 optimal locations for targeted WNV surveillance campaigns in the United States-Illinois, New York, and Texas. These results illustrate the value of multidisciplinary approaches to surveillance of infectious diseases, especially zoonotic diseases.
Topics: Animal Migration; Animals; Bayes Theorem; Birds; High-Throughput Nucleotide Sequencing; Humans; Incidence; Phylogeny; Phylogeography; RNA, Viral; United States; West Nile Fever; West Nile virus
PubMed: 30457531
DOI: 10.3201/eid2412.180382 -
PLoS Neglected Tropical Diseases Dec 2018West Nile virus (WNV) and Zika virus (ZIKV) are mosquito-borne viral infections. Over the past few decades, WNV has been associated with several outbreaks involving high...
West Nile virus (WNV) and Zika virus (ZIKV) are mosquito-borne viral infections. Over the past few decades, WNV has been associated with several outbreaks involving high numbers of neuroinvasive diseases among humans. The recent re-emergence of ZIKV has been associated with congenital malformation and also with Guillain-Barre syndrome in adults. The geographic range of arthropod-borne viruses has been rapidly increasing in recent years. The objectives of this study were to determine the presence of IgG specific antibodies and the genome of WNV and ZIKV in human samples, as well as WNV and ZIKV genomes in wild-caught mosquitoes in urban and rural areas of the Hormozgan province, in southern Iran. A total of 494 serum samples were tested for the presence of WNV and ZIKV IgG antibodies using ELISA assays. One hundred and two (20.6%) samples were reactive for WNV IgG antibodies. All serum samples were negative for ZIKV IgG antibodies. Using the multivariable logistic analysis, age (45+ vs. 1-25; OR = 3.4, 95% C.I.: 1.8-6.3), occupation (mostly outdoor vs. mostly indoor; OR = 2.4, 95% C.I.: 1.1-5.2), and skin type(type I/II vs. type III/IV and type V/VI; OR = 4.3, 95% C.I.: 1.7-10.8 and OR = 2.7, 95% C.I.: 1.3-5.5 respectively, skin types based on Fitzpatrick scale) showed significant association with WNV seroreactivity. We collected 2,015 mosquitoes in 136 pools belonging to 5 genera and 14 species. Three pools of Culex pipiens complex were positive for WNV RNA using real-time reverse transcription polymerase chain reaction (rtRT-PCR). ZIKV RNA was not detected in any of the pools. All WNV ELISA reactive serum samples were negative for WNV RNA. In conclusion, we provided evidence of the establishment of WNV in southern Iran and no proof of ZIKV in serum samples or in mosquito vectors. The establishment of an organized arbovirus surveillance system and active case finding strategies seems to be necessary.
Topics: Adolescent; Adult; Animals; Antibodies, Viral; Child; Child, Preschool; Female; Humans; Infant; Iran; Male; Middle Aged; West Nile Fever; West Nile virus; Young Adult; Zika Virus; Zika Virus Infection
PubMed: 30557321
DOI: 10.1371/journal.pntd.0007022 -
Parasites & Vectors Jun 2023Mosquitoes in the genus Culex are primary vectors in the US for West Nile virus (WNV) and other arboviruses. Climatic drivers such as temperature have differential... (Review)
Review
BACKGROUND
Mosquitoes in the genus Culex are primary vectors in the US for West Nile virus (WNV) and other arboviruses. Climatic drivers such as temperature have differential effects on species-specific changes in mosquito range, distribution, and abundance, posing challenges for population modeling, disease forecasting, and subsequent public health decisions. Understanding these differences in underlying biological dynamics is crucial in the face of climate change.
METHODS
We collected empirical data on thermal response for immature development rate, egg viability, oviposition, survival to adulthood, and adult lifespan for Culex pipiens, Cx. quinquefasciatus, Cx. tarsalis, and Cx. restuans from existing literature according to the PRISMA scoping review guidelines.
RESULTS
We observed linear relationships with temperature for development rate and lifespan, and nonlinear relationships for survival and egg viability, with underlying variation between species. Optimal ranges and critical minima and maxima also appeared varied. To illustrate how model output can change with experimental input data from individual Culex species, we applied a modified equation for temperature-dependent mosquito type reproduction number for endemic spread of WNV among mosquitoes and observed different effects.
CONCLUSIONS
Current models often input theoretical parameters estimated from a single vector species; we show the need to implement the real-world heterogeneity in thermal response between species and present a useful data resource for researchers working toward that goal.
Topics: Animals; Female; Culex; Culicidae; Life History Traits; Mosquito Vectors; Temperature; West Nile virus
PubMed: 37316915
DOI: 10.1186/s13071-023-05792-3