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Current Opinion in Virology Dec 2016West Nile virus remains the most common cause of arboviral encephalitis in North America. Since it was introduced, it has undergone adaptive genetic change as it spread... (Review)
Review
West Nile virus remains the most common cause of arboviral encephalitis in North America. Since it was introduced, it has undergone adaptive genetic change as it spread throughout the continent. The WNV transmission cycle is relatively tractable in the laboratory. Thus the virus serves as a convenient model system for studying the population biology of mosquito-borne flaviviruses as they undergo transmission to and from mosquitoes and vertebrates. This review summarizes the current knowledge regarding the population dynamics of this virus within mosquito vectors.
Topics: Adaptation, Biological; Animals; Mosquito Vectors; North America; Population Dynamics; West Nile virus
PubMed: 27788400
DOI: 10.1016/j.coviro.2016.09.007 -
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 -
Frontiers in Immunology 2022Dietary fiber supports healthy gut bacteria and their production of short-chain fatty acids (SCFA), which promote anti-inflammatory cell development, in particular,...
Dietary fiber supports healthy gut bacteria and their production of short-chain fatty acids (SCFA), which promote anti-inflammatory cell development, in particular, regulatory T cells. It is thus beneficial in many diseases, including influenza infection. While disruption of the gut microbiota by antibiotic treatment aggravates West Nile Virus (WNV) disease, whether dietary fiber is beneficial is unknown. WNV is a widely-distributed neurotropic flavivirus that recruits inflammatory monocytes into the brain, causing life-threatening encephalitis. To investigate the impact of dietary fiber on WNV encephalitis, mice were fed on diets deficient or enriched with dietary fiber for two weeks prior to inoculation with WNV. To induce encephalitis, mice were inoculated intranasally with WNV and maintained on these diets. Despite increased fecal SCFA acetate and changes in gut microbiota composition, dietary fiber did not affect clinical scores, leukocyte infiltration into the brain, or survival. After the brain, highest virus loads were measured in the colon in neurons of the submucosal and myenteric plexuses. Associated with this, there was disrupted gut homeostasis, with shorter colon length and higher local inflammatory cytokine levels, which were not affected by dietary fiber. Thus, fiber supplementation is not effective in WNV encephalitis.
Topics: Animals; Brain; Cytokines; Dietary Fiber; Mice; West Nile Fever; West Nile virus
PubMed: 35296081
DOI: 10.3389/fimmu.2022.784486 -
Viruses Apr 2020West Nile virus (WNV) lineage 2 is expanding and causing large outbreaks in Europe. In this study, we analyzed the epidemiological, clinical, and virological features of...
West Nile virus (WNV) lineage 2 is expanding and causing large outbreaks in Europe. In this study, we analyzed the epidemiological, clinical, and virological features of WNV lineage 2 infection during the large outbreak that occurred in northern Italy in 2018. The study population included 86 patients with neuroinvasive disease (WNND), 307 with fever (WNF), and 34 blood donors. Phylogenetic analysis of WNV full genome sequences from patients' samples showed that the virus belonged to the widespread central/southern European clade of WNV lineage 2 and was circulating in the area at least since 2014. The incidence of WNND and WNF progressively increased with age and was higher in males than in females. Among WNND patients, the case fatality rate was 22%. About 70% of blood donors reported symptoms during follow-up. Within the first week after symptom onset, WNV RNA was detectable in the blood or urine of 80% of patients, while 20% and 40% of WNND and WNF patients, respectively, were WNV IgM-seronegative. In CSF samples of WNND patients, WNV RNA was typically detectable when WNV IgM antibodies were absent. Blunted or no WNV IgM response and high WNV IgG levels were observed in seven patients with previous flavivirus immunity.
Topics: Aged; Aged, 80 and over; Animals; Antibodies, Viral; Culicidae; Disease Outbreaks; Female; Genome, Viral; Geography, Medical; Humans; Immunoglobulin G; Immunoglobulin M; Incidence; Male; Middle Aged; Public Health Surveillance; West Nile Fever; West Nile virus
PubMed: 32325716
DOI: 10.3390/v12040458 -
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 -
Veterinaria Italiana Sep 2017West Nile virus (WNV) is an arthropod borne virus of public health importance. The virus is a member of the genus Flavivirus and belongs to the Japanese encephalitis... (Review)
Review
West Nile virus (WNV) is an arthropod borne virus of public health importance. The virus is a member of the genus Flavivirus and belongs to the Japanese encephalitis virus (JEV) antigenic complex under the Flaviviridae family. The WNV is continuously spreading across Tunisia especially in the coastal and Southern area of the country. The first human West Nile disease (WND) epidemic in Tunisia occurred in 1997, since then, the quantity and the extension of spillover effects increased constantly. However, the existing knowledge of factors triggering such events continues to be rather poor. The last epidemic WNV human meningitis and meningoencephalitis recorded in 2012, with 86 cases and 6 deaths, confirmed the failure of the current system in predicting new cases. This review, based on analysis of scientific papers published between 1970 and 2015, summarises the state of knowledge on WNV in Tunisia and highlights the existing knowledge and research gaps that need to be addressed.
Topics: Animals; Epidemiological Monitoring; Humans; Time Factors; Tunisia; West Nile Fever; West Nile virus
PubMed: 29152704
DOI: 10.12834/VetIt.1181.6565.2 -
Virologica Sinica Feb 2019The family of flaviviruses is one of the most medically important groups of emerging arthropod-borne viruses. Host cell cytoskeletons have been reported to have close... (Review)
Review
The family of flaviviruses is one of the most medically important groups of emerging arthropod-borne viruses. Host cell cytoskeletons have been reported to have close contact with flaviviruses during virus entry, intracellular transport, replication, and egress process, although many detailed mechanisms are still unclear. This article provides a brief overview of the function of the most prominent flaviviruses-induced or -hijacked cytoskeletal structures including actin, microtubules and intermediate filaments, mainly focus on infection by dengue virus, Zika virus and West Nile virus. We suggest that virus interaction with host cytoskeleton to be an interesting area of future research.
Topics: Actins; Animals; Cytoskeleton; Dengue Virus; Flavivirus; Flavivirus Infections; Host Microbial Interactions; Humans; Intermediate Filaments; Mice; Microtubules; Virus Internalization; Virus Replication; West Nile virus; Zika Virus
PubMed: 30725318
DOI: 10.1007/s12250-019-00086-4 -
Journal of Virology Sep 2021Dengue virus (DENV) and West Nile virus (WNV) are arthropod-transmitted flaviviruses that cause systemic vascular leakage and encephalitis syndromes, respectively, in...
Dengue virus (DENV) and West Nile virus (WNV) are arthropod-transmitted flaviviruses that cause systemic vascular leakage and encephalitis syndromes, respectively, in humans. However, the viral factors contributing to these specific clinical disorders are not completely understood. Flavivirus nonstructural protein 1 (NS1) is required for replication, expressed on the cell surface, and secreted as a soluble glycoprotein, reaching high levels in the blood of infected individuals. Extracellular DENV NS1 and WNV NS1 interact with host proteins and cells, have immune evasion functions, and promote endothelial dysfunction in a tissue-specific manner. To characterize how differences in DENV NS1 and WNV NS1 might function in pathogenesis, we generated WNV NS1 variants with substitutions corresponding to residues found in DENV NS1. We discovered that the substitution NS1-P101K led to reduced WNV infectivity in the brain and attenuated lethality in infected mice, although the virus replicated efficiently in cell culture and peripheral organs and bound at wild-type levels to brain endothelial cells and complement components. The P101K substitution resulted in reduced NS1 antigenemia in mice, and this was associated with reduced WNV spread to the brain. Because exogenous administration of NS1 protein rescued WNV brain infectivity in mice, we conclude that circulating WNV NS1 facilitates viral dissemination into the central nervous system and impacts disease outcomes. Flavivirus NS1 serves as an essential scaffolding molecule during virus replication but also is expressed on the cell surface and is secreted as a soluble glycoprotein that circulates in the blood of infected individuals. Although extracellular forms of NS1 are implicated in immune modulation and in promoting endothelial dysfunction at blood-tissue barriers, it has been challenging to study specific effects of NS1 on pathogenesis without disrupting its key role in virus replication. Here, we assessed WNV NS1 variants that do not affect virus replication and evaluated their effects on pathogenesis in mice. Our characterization of WNV NS1-P101K suggests that the levels of NS1 in the circulation facilitate WNV dissemination to the brain and affect disease outcomes. Our findings facilitate understanding of the role of NS1 during flavivirus infection and support antiviral strategies for targeting circulating forms of NS1.
Topics: Animals; Brain; Dengue Virus; Endothelial Cells; Female; Flavivirus; Immune Evasion; Male; Mice; Mice, Inbred C57BL; Viral Nonstructural Proteins; Virus Replication; West Nile Fever; West Nile virus
PubMed: 34346770
DOI: 10.1128/JVI.00844-21 -
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 -
PLoS Neglected Tropical Diseases Nov 2020The California Arbovirus Surveillance Program was initiated over 50 years ago to track endemic encephalitides and was enhanced in 2000 to include West Nile virus (WNV)...
The California Arbovirus Surveillance Program was initiated over 50 years ago to track endemic encephalitides and was enhanced in 2000 to include West Nile virus (WNV) infections in humans, mosquitoes, sentinel chickens, dead birds and horses. This comprehensive statewide program is a function of strong partnerships among the California Department of Public Health (CDPH), the University of California, and local vector control and public health agencies. This manuscript summarizes WNV surveillance data in California since WNV was first detected in 2003 in southern California. From 2003 through 2018, 6,909 human cases of WNV disease, inclusive of 326 deaths, were reported to CDPH, as well as 730 asymptomatic WNV infections identified during screening of blood and organ donors. Of these, 4,073 (59.0%) were reported as West Nile neuroinvasive disease. California's WNV disease burden comprised 15% of all cases that were reported to the U.S. Centers for Disease Control and Prevention during this time, more than any other state. Additionally, 1,299 equine WNV cases were identified, along with detections of WNV in 23,322 dead birds, 31,695 mosquito pools, and 7,340 sentinel chickens. Annual enzootic detection of WNV typically preceded detection in humans and prompted enhanced intervention to reduce the risk of WNV transmission. Peak WNV activity occurred from July through October in the Central Valley and southern California. Less than five percent of WNV activity occurred in other regions of the state or outside of this time. WNV continues to be a major threat to public and wild avian health in California, particularly in southern California and the Central Valley during summer and early fall months. Local and state public health partners must continue statewide human and mosquito surveillance and facilitate effective mosquito control and bite prevention measures.
Topics: Animals; Base Sequence; Birds; California; Chickens; Culex; Epidemiological Monitoring; Horses; Humans; Mosquito Vectors; RNA, Viral; Seasons; Sequence Analysis, RNA; West Nile Fever; West Nile virus
PubMed: 33206634
DOI: 10.1371/journal.pntd.0008841