scholarly journals Molecular Determinants of West Nile Virus Virulence and Pathogenesis in Vertebrate and Invertebrate Hosts

2020 ◽  
Vol 21 (23) ◽  
pp. 9117
Author(s):  
Lise Fiacre ◽  
Nonito Pagès ◽  
Emmanuel Albina ◽  
Jennifer Richardson ◽  
Sylvie Lecollinet ◽  
...  

West Nile virus (WNV), like the dengue virus (DENV) and yellow fever virus (YFV), are major arboviruses belonging to the Flavivirus genus. WNV is emerging or endemic in many countries around the world, affecting humans and other vertebrates. Since 1999, it has been considered to be a major public and veterinary health problem, causing diverse pathologies, ranging from a mild febrile state to severe neurological damage and death. WNV is transmitted in a bird–mosquito–bird cycle, and can occasionally infect humans and horses, both highly susceptible to the virus but considered dead-end hosts. Many studies have investigated the molecular determinants of WNV virulence, mainly with the ultimate objective of guiding vaccine development. Several vaccines are used in horses in different parts of the world, but there are no licensed WNV vaccines for humans, suggesting the need for greater understanding of the molecular determinants of virulence and antigenicity in different hosts. Owing to technical and economic considerations, WNV virulence factors have essentially been studied in rodent models, and the results cannot always be transported to mosquito vectors or to avian hosts. In this review, the known molecular determinants of WNV virulence, according to invertebrate (mosquitoes) or vertebrate hosts (mammalian and avian), are presented and discussed. This overview will highlight the differences and similarities found between WNV hosts and models, to provide a foundation for the prediction and anticipation of WNV re-emergence and its risk of global spread.

2019 ◽  
Vol 56 (6) ◽  
pp. 1463-1466
Author(s):  
Angela M Bosco-Lauth ◽  
Richard A Bowen

Abstract West Nile virus (WNV) (Flaviviridae: Flavivirus) was discovered in Africa more than 80 yr ago and became recognized as an avian pathogen and a cause of neurologic disease in horses largely during periodic incursions into Europe. Introduction of WNV into North America stimulated great anxiety, particularly in the equine industry, but also for pet owners and livestock producers concerned about the effect of WNV on other domestic animals. Numerous subsequent studies of naturally occurring and experimentally induced disease greatly expanded our understanding of the host range and clinical consequences of WNV infection in diverse species and led to rapid development and deployment of efficacious vaccines for horses. In addition to humans, horses are clearly the animals most frequently affected by serious, sometimes lethal disease following infection with WNV, but are dead-end hosts due to the low-magnitude viremia they develop. Dogs, cats, and livestock species including chickens are readily infected with WNV, but only occasionally develop clinical disease and are considered dead-end hosts for the virus.


Author(s):  
Hamid Staji ◽  
Morteza Keyvanlou ◽  
Zeinab Geraili ◽  
Hedyeh Shahsavari ◽  
Elnaz Jafari

Background: West Nile Virus (WNV) is an arboviral infection continuing to be as major threat to human health as well as the livestock industry all around the world. Birds including pigeons are one of the potential reservoirs for WNV. This study aimed to detect the presence of WNV genome in feral pigeons circulating in Semnan and Khorasane-Razavi Provinces (Iran) including 10 urban and 10 suburban areas. Methods: Totally, 150 samples (brain and kidney) were collected equally from feral pigeons and the presence of WNV genome was evaluated in these samples after RNA extraction. Results: All the samples were negative for the presence of WNV-RNA in this investigation. Conclusion: Although obtained result indicated no evidence of WNV genome in feral pigeons but complementary studies regarding serologic detection of WNV in vertebrate hosts as well as pigeons and identification of arthropod vectors seems necessary for comprehensive determination about infection status in these areas.  


Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1073
Author(s):  
Juan-Carlos Saiz

West Nile virus (WNV) is a widely distributed enveloped flavivirus transmitted by mosquitoes, which main hosts are birds. The virus sporadically infects equids and humans with serious economic and health consequences, as infected individuals can develop a severe neuroinvasive disease that can even lead to death. Nowadays, no WNV-specific therapy is available and vaccines are only licensed for use in horses but not for humans. While several methodologies for WNV vaccine development have been successfully applied and have contributed to significantly reducing its incidence in horses in the US, none have progressed to phase III clinical trials in humans. This review addresses the status of WNV vaccines for horses, birds, and humans, summarizing and discussing the challenges they face for their clinical advance and their introduction to the market.


2019 ◽  
Vol 268 ◽  
pp. 53-55 ◽  
Author(s):  
José A. Boga ◽  
Marta E. Alvarez-Arguelles ◽  
Susana Rojo-Alba ◽  
Mercedes Rodríguez ◽  
María de Oña ◽  
...  

Author(s):  
Jooyeon Park ◽  
Jinhwa Jang ◽  
Insung Ahn

The Zika virus (ZIKV) belongs to the genus Flavivirus, together with Dengue virus, yellow fever virus, and West Nile virus. The virus, which was first found in Africa in 1947, has spread across the world owing to a lack of effective drugs or vaccines. The complete genome sequence of ZIKV is now available; it includes three structural and seven non-structure genes arranged in the order of capsid, pre-membrane, envelope, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. Two geographically distinct lineages are known, i.e., Asian and African, but ZIKV exhibits differences in clinical progression among regions.


mSphere ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Jessica J. Harrison ◽  
Jody Hobson-Peters ◽  
Agathe M. G. Colmant ◽  
Joanna Koh ◽  
Natalee D. Newton ◽  
...  

ABSTRACT We describe two new insect-specific flaviviruses (ISFs) isolated from mosquitoes in Australia, Binjari virus (BinJV) and Hidden Valley virus (HVV), that grow efficiently in mosquito cells but fail to replicate in a range of vertebrate cell lines. Phylogenetic analysis revealed that BinJV and HVV were closely related (90% amino acid sequence identity) and clustered with lineage II (dual-host affiliated) ISFs, including the Lammi and Nounané viruses. Using a panel of monoclonal antibodies prepared to BinJV viral proteins, we confirmed a close relationship between HVV and BinJV and revealed that they were antigenically quite divergent from other lineage II ISFs. We also constructed chimeric viruses between BinJV and the vertebrate-infecting West Nile virus (WNV) by swapping the structural genes (prM and E) to produce BinJ/WNVKUN-prME and WNVKUN/BinJV-prME. This allowed us to assess the role of different regions of the BinJV genome in vertebrate host restriction and revealed that while BinJV structural proteins facilitated entry to vertebrate cells, the process was inefficient. In contrast, the BinJV replicative components in wild-type BinJV and BinJ/WNVKUN-prME failed to initiate replication in a wide range of vertebrate cell lines at 37°C, including cells lacking components of the innate immune response. However, trace levels of replication of BinJ/WNVKUN-prME could be detected in some cultures of mouse embryo fibroblasts (MEFs) deficient in antiviral responses (IFNAR−/− MEFs or RNase L−/− MEFs) incubated at 34°C after inoculation. This suggests that BinJV replication in vertebrate cells is temperature sensitive and restricted at multiple stages of cellular infection, including inefficient cell entry and susceptibility to antiviral responses. IMPORTANCE The globally important flavivirus pathogens West Nile virus, Zika virus, dengue viruses, and yellow fever virus can infect mosquito vectors and be transmitted to humans and other vertebrate species in which they cause significant levels of disease and mortality. However, the subgroup of closely related flaviviruses, known as lineage II insect-specific flaviviruses (Lin II ISFs), only infect mosquitoes and cannot replicate in cells of vertebrate origin. Our data are the first to uncover the mechanisms that restrict the growth of Lin II ISFs in vertebrate cells and provides new insights into the evolution of these viruses and the mechanisms associated with host switching that may allow new mosquito-borne viral diseases to emerge. The new reagents generated in this study, including the first Lin II ISF-reactive monoclonal antibodies and Lin II ISF mutants and chimeric viruses, also provide new tools and approaches to enable further research advances in this field.


Author(s):  
Erica Azevedo Costa ◽  
José Joffre Martins Bayeux ◽  
Aila Solimar Gonçalves Silva ◽  
Guilherme Alves De Queiroz ◽  
Beatriz Senra Álvares da Silva Santos ◽  
...  

West Nile virus (WNV) is a neurovirulent mosquito-borne Flavivirus that is maintained in nature by a zoonotic transmissioncycle between avian hosts and ornithophilic mosquito vectors, mostly from the Culex genus. Until the 1990s, WNV wasconsidered to be an old-world arbovirus, but in 1999, WNV emerged in the United States (US) and spread rapidly, becoming amajor threat to public health. WNV adapted to the transmission cycle involving American mosquitoes and birds and reachedCentral and South America in subsequent years. In 2003, the National West Nile Fever Surveillance System was created in Brazilbased on serological screening of animals and sentinel vectors, as recommended by the Pan American Health Organization(PAHO) and the World Health Organization (WHO). Since 2008, serological evidence of WNV infection in Brazilian horseshas been reported, and the circulation of WNV has been monitored through the regular serological screening of sentinel horsesand reporting of encephalomyelitis cases. Horses are highly susceptible to WNV infection, and outbreaks of neurologicaldisease among horses often precede human cases. In this regard, equine surveillance has been essential in providing earlywarning to public and animal health authorities in several countries, including Brazil. This demonstrates the need for animaland public health intervention programs to allocate resources to make veterinarians aware of the role they can play in thehuman surveillance processes by monitoring horses. This review discusses the importance of equine surveillance and the gapthat veterinarians can fill on the front line in human surveillance, in Brazil and worldwide, in the context of “One Health”


Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 823 ◽  
Author(s):  
Jaclyn A. Kaiser ◽  
Alan D.T. Barrett

Although West Nile virus (WNV) has been a prominent mosquito-transmitted infection in North America for twenty years, no human vaccine has been licensed. With a cumulative number of 24,714 neurological disease cases and 2314 deaths in the U.S. since 1999, plus a large outbreak in Europe in 2018 involving over 2000 human cases in 15 countries, a vaccine is essential to prevent continued morbidity, mortality, and economic burden. Currently, four veterinary vaccines are licensed, and six vaccines have progressed into clinical trials in humans. All four veterinary vaccines require multiple primary doses and annual boosters, but for a human vaccine to be protective and cost effective in the most vulnerable older age population, it is ideal that the vaccine be strongly immunogenic with only a single dose and without subsequent annual boosters. Of six human vaccine candidates, the two live, attenuated vaccines were the only ones that elicited strong immunity after a single dose. As none of these candidates have yet progressed beyond phase II clinical trials, development of new candidate vaccines and improvement of vaccination strategies remains an important area of research.


Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 720
Author(s):  
Nataša Knap ◽  
Miša Korva ◽  
Vladimir Ivović ◽  
Katja Kalan ◽  
Mateja Jelovšek ◽  
...  

West Nile virus (WNV) is a flavivirus transmitted by mosquitoes. Birds are the reservoir for the virus; humans, horses and other mammals are dead-end hosts. Infections caused by WNV in humans can vary from asymptomatic infections to West Nile fever (WNF) or West Nile neuroinvasive disease (WNND). In 1995, a serosurvey was performed in Slovenia on forest workers, and WNV specific IgG antibodies were confirmed in 6.8% of the screened samples, indicating that WNV is circulating in Slovenia. No human disease cases were detected in Slovenia until 2013, when the first case of WNV infection was confirmed in a retrospective study in a 79-year old man with meningitis. In 2018, three patients with WNND were confirmed by laboratory tests, with detection of IgM antibodies in the cerebrospinal fluid of the patients. In one of the patients, WNV RNA was detected in the urine sample. In 2017, 2018 and 2019, a mosquito study was performed in Slovenia. Mosquitoes were sampled on 14 control locations and 35 additional locations in 2019. No WNV was detected in mosquitoes in 2017 and 2019, but we confirmed the virus in a pool of Culex sp. mosquitoes in 2018. The virus was successfully isolated, and complete genome sequence was acquired. The whole genome of the WNV was also sequenced from the patient’s urine sample. The whole genome sequences of the WNV virus detected in Slovenian patient and mosquito indicate the virus most likely spread from the north, because of the geographic proximity and because the sequences cluster with the Austrian and Hungarian sequences. A sentinel study was performed on dog sera samples, and we were able to confirm IgG antibodies in 1.8% and 4.3% of the samples in 2017 and 2018, respectively. Though Slovenia is not a highly endemic country for WNV, we have established that the virus circulates in Slovenia.


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