Sample records for nile virus predictive

  1. Impacts of West Nile Virus on wildlife

    USGS Publications Warehouse

    Saito, E.K.; Wild, M.A.

    2004-01-01

    The recent epidemic of West Nile virus in the United States proved to be unexpectedly active and was the largest epidemic of the virus ever recorded. Much remains to be discovered about the ecology and epidemiology of West Nile virus in the United States, including which species are important in maintaining the virus in nature, why some species are more susceptible to lethal infection, and what environmental factors are important in predicting future epidemics. These factors will likely vary regionally, depending on local ecological characteristics. Until scientists better understand the virus and factors influencing its activity, predicting its effects for future seasons is impossible. However, experts are certain about one thing: West Nile virus is here to stay.

  2. What's West Nile Virus?

    MedlinePlus

    ... for Educators Search English Español What's West Nile Virus? KidsHealth / For Kids / What's West Nile Virus? Print en español ¿Qué es el Virus del Nilo Occidental? What exactly is the West ...

  3. West Nile virus: North American experience

    USGS Publications Warehouse

    Hofmeister, Erik K.

    2011-01-01

    West Nile virus, a mosquito-vectored flavivirus of the Japanese encephalitis serogroup, was first detected in North America following an epizootic in the New York City area in 1999. In the intervening 11 years since the arrival of the virus in North America, it has crossed the contiguous USA, entered the Canadian provinces bordering the USA, and has been reported in the Caribbean islands, Mexico, Central America and, more recently, South America. West Nile virus has been reported in over 300 species of birds in the USA and has caused the deaths of thousands of birds, local population declines of some avian species, the clinical illness and deaths of thousands of domestic horses, and the clinical disease in over 30 000 Americans and the deaths of over 1000. Prior to the emergence of West Nile virus in North America, St. Louis encephalitis virus and Dengue virus were the only other known mosquito-transmitted flaviviruses in North America capable of causing human disease. This review will discuss the North American experience with mosquito-borne flavivirus prior to the arrival of West Nile virus, the entry and spread of West Nile virus in North America, effects on wild bird populations, genetic changes in the virus, and the current state of West Nile virus transmission.

  4. Predicting pathogen introduction: West Nile virus spread to Galáipagos.

    PubMed

    Kilpatrick, A Marm; Daszak, Peter; Goodman, Simon J; Rogg, Helmuth; Kramer, Laura D; Cedeño, Virna; Cunningham, Andrew A

    2006-08-01

    Emerging infectious diseases are a key threat to conservation and public health, yet predicting and preventing their emergence is notoriously difficult. We devised a predictive model for the introduction of a zoonotic vector-borne pathogen by considering each of the pathways by which it may be introduced to a new area and comparing the relative risk of each pathway. This framework is an adaptation of pest introduction models and estimates the number of infectious individuals arriving in a location and the duration of their infectivity. We used it to determine the most likely route for the introduction of West Nile virus to Galápagos and measures that can be taken to reduce the risk of introduction. The introduction of this highly pathogenic virus to this unique World Heritage Site could have devastating consequences, similar to those seen following introductions of pathogens into other endemic island faunas. Our model identified the transport of mosquitoes on airplanes as the highest risk for West Nile virus introduction. Pathogen dissemination through avian migration and the transportation of day-old chickens appeared to be less important pathways. Infected humans and mosquitoes transported in sea containers, in tires, or by wind all represented much lower risk. Our risk-assessment framework has broad applicability to other pathogens and other regions and depends only on the availability of data on the transport of goods and animals and the epidemiology of the pathogen.

  5. West Nile Virus and wildlife

    USGS Publications Warehouse

    Marra, P.P.; Griffing, S.; Caffrey, C.; Kilpatrick, A.M.; McLean, R.; Brand, C.; Saito, E.; Dupuis, A.P.; Kramer, Laura; Novak, R.

    2004-01-01

    West Nile virus (WNV) has spread rapidly across North America, resulting in human deaths and in the deaths of untold numbers of birds, mammals, and reptiles. The virus has reached Central America and the Caribbean and may spread to Hawaii and South America. Although tens of thousands of birds have died, and studies of some bird species show local declines, few regionwide declines can be attributed to WNV. Predicting future impacts of WNV on wildlife, and pinpointing what drives epidemics, will require substantial additional research into host susceptibility, reservoir competency, and linkages between climate, mosquitoes, and disease. Such work will entail a collaborative effort between scientists in governmental research groups, in surveillance and control programs, and in nongovernmental organizations. West Nile virus was not the first, and it will not be the last, exotic disease to be introduced to the New World. Its spread in North America highlights the need to strengthen animal monitoring programs and to integrate them with research on disease ecology.

  6. West Nile Virus: Symptoms and Treatment

    MedlinePlus

    ... U V W X Y Z # West Nile virus Note: Javascript is disabled or is not supported ... visit this page: About CDC.gov . West Nile Virus Home Prevention Prevención y control Symptoms, Diagnosis, & Treatment ...

  7. West Nile Virus Infection in Sheep.

    PubMed

    Rimoldi, G; Mete, A; Adaska, J M; Anderson, M L; Symmes, K P; Diab, S

    2017-01-01

    West Nile virus (WNV) infection has been detected in many species of birds and mammals, but scant information is available about the disease in small ruminants. West Nile virus was diagnosed in 6 sheep with neurological signs and encephalitis, in California between 2002 and 2014. All sheep had severe lymphoplasmacytic meningoencephalitis. Lymphoplasmacytic myelitis was also detected in 2 sheep where the spinal cord was examined. Brain tissue was positive for WNV detected by polymerase chain reaction in 6 of 6 sheep and by immunohistochemistry (IHC) in 5 of 6 sheep. Viral antigen was not detected by IHC in extraneural tissues in the 3 sheep examined. West Nile virus RNA was sequenced from 2 of 6 sheep, and each one clusters closely with WNV isolated from mosquito pools from nearby locations at similar times. West Nile virus was the most common cause of viral encephalitis in sheep diagnosed at this laboratory between 2002 and 2014, accounting for 6 of 9 sheep.

  8. 21 CFR 866.3940 - West Nile virus serological reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false West Nile virus serological reagents. 866.3940... virus serological reagents. (a) Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum...

  9. 21 CFR 866.3940 - West Nile virus serological reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false West Nile virus serological reagents. 866.3940... virus serological reagents. (a) Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum...

  10. 21 CFR 866.3940 - West Nile virus serological reagents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false West Nile virus serological reagents. 866.3940... virus serological reagents. (a) Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum...

  11. 21 CFR 866.3940 - West Nile virus serological reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false West Nile virus serological reagents. 866.3940... virus serological reagents. (a) Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum...

  12. 21 CFR 866.3940 - West Nile virus serological reagents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false West Nile virus serological reagents. 866.3940... virus serological reagents. (a) Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum...

  13. Reactivation West Nile virus infection-related chorioretinitis.

    PubMed

    Beardsley, Robert; McCannel, Colin

    2012-01-01

    West Nile Virus is a relatively uncommon infection that can involve retinal and choroidal inflammation leading to photopsias, photophobia, and orbital pain. The diagnosis is made by clinical history, serology, and characteristic funduscopic exam and fluorescein angiography findings. Treatment involves primarily supportive care as there are no known effective anti-viral agents. Visual recovery is usually full. Here we present a case of West Nile Virus Infection Related chorioretinitis that demonstrated active linear chorioretinal lesions approximately one year after the initial infection was diagnosed and treated. The patient noted new onset blurry vision and floaters for two weeks prior to presentation. Antibody titers to West Nile Virus increased from baseline levels indicating active infection. This represents the first case of reactivation West Nile Virus Infection Related chorioretinitis that has been documented.

  14. Monitoring the Spread of West Nile Virus with Satellite Data

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA-funded study uses temperature and vegetation data from satellites to help track and predict where West Nile virus is spreading in North America. Scientists and public health officials hope one day to use near real-time maps to focus resources and stave off the disease more efficiently. This image is a composite of land surface temperatures (LST) recorded between 1997 and 2000 and was used to help monitor and predict the spread of West Nile virus in the United States. In the color figure above, the mean land surface temperatures are in red; annual amplitude-or the difference between low and high annual temperatures-is in blue; and annual phase-or the timing of annual temperature peaks-appears in green. Brighter colors mean higher values. The major north-south temperature difference (dull red in the upper part of the image to bright red in the lower part) is considerably affected by the Rockies in the west and to a much lesser extent by the Appalachians in the east. The brighter blue in the upper part of the image indicates the big difference between highest and lowest temperatures during the course of a year at higher latitudes. There is less variation in the timing of the annual peak of land surface temperatures, which occurs earlier in the south than in the north. Black dots superimposed on this image are the locations (county geo-centers) where birds infected with West Nile virus were reported between January and October 2001. Scientists working with the International Research Partnership for Infectious Diseases (INTREPID) program based at NASA are using such imagery to define and predict the conditions where mosquitoes transmit West Nile virus in the U.S. The conclusion reached about the importance of any single variable depends both upon its value and context. A temperature of 30o Celsius (86o Fahrenheit) might be fatal for a mosquito at low humidity but survivable at higher humidities. The work done here on West Nile virus and other diseases shows very

  15. Yellow fever vector live-virus vaccines: West Nile virus vaccine development.

    PubMed

    Arroyo, J; Miller, C A; Catalan, J; Monath, T P

    2001-08-01

    By combining molecular-biological techniques with our increased understanding of the effect of gene sequence modification on viral function, yellow fever 17D, a positive-strand RNA virus vaccine, has been manipulated to induce a protective immune response against viruses of the same family (e.g. Japanese encephalitis and dengue viruses). Triggered by the emergence of West Nile virus infections in the New World afflicting humans, horses and birds, the success of this recombinant technology has prompted the rapid development of a live-virus attenuated candidate vaccine against West Nile virus.

  16. West Nile Virus: Review of the Literature

    PubMed Central

    Petersen, Lyle R.; Brault, Aaron C.; Nasci, Roger S.

    2015-01-01

    IMPORTANCE Since its introduction in North America in 1999,West Nile virus has produced the 3 largest arboviral neuroinvasive disease outbreaks ever recorded in the United States. OBJECTIVE To review the ecology, virology, epidemiology, clinical characteristics, diagnosis, prevention, and control of West Nile virus, with an emphasis on North America. EVIDENCE REVIEW PubMed electronic database was searched through February 5, 2013. United States national surveillance data were gathered from the Centers for Disease Control and Prevention. FINDINGS West Nile virus is now endemic throughout the contiguous United States, with 16 196 human neuroinvasive disease cases and 1549 deaths reported since 1999. More than 780 000 illnesses have likely occurred. To date, incidence is highest in the Midwest from mid-July to early September. West Nile fever develops in approximately 25% of those infected, varies greatly in clinical severity, and symptoms may be prolonged. Neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis) develops in less than 1% but carries a fatality rate of approximately 10%. Encephalitis has a highly variable clinical course but often is associated with considerable long-term morbidity. Approximately two-thirds of those with paralysis remain with significant weakness in affected limbs. Diagnosis usually rests on detection of IgM antibody in serum or cerebrospinal fluid. Treatment is supportive; no licensed human vaccine exists. Prevention uses an integrated pest management approach, which focuses on surveillance, elimination of mosquito breeding sites, and larval and adult mosquito management using pesticides to keep mosquito populations low. During outbreaks or impending outbreaks, emphasis shifts to aggressive adult mosquito control to reduce the abundance of infected, biting mosquitoes. Pesticide exposure and adverse human health events following adult mosquito control operations for West Nile virus appear negligible. CONCLUSIONS AND

  17. A study of West Nile virus infection in Iranian blood donors.

    PubMed

    Sharifi, Zohreh; Mahmoodian Shooshtari, Mahmood; Talebian, Ali

    2010-01-01

    West Nile virus is a mosquito transmitted virus that can cause disease in humans and horses. A majority of people infected with WNV will have no symptoms or may only experience mild symptoms, such as headaches. About 20% of infected humans develop a flu-like illness characterized by fever; while in the elderly and immunocompromised West Nile virus can cause a more serious neurologic disease and may be fatal. West Nile virus infection is endemic in the Middle East. West Nile virus can also be transmitted by transfusion through infected blood components.The objective of this study is to find the West Nile virus-RNA incidence and anti-West Nile virus prevalence amongst Iranian blood donors in order to determine whether this emerging infection is a possible risk for the blood supply in Iran. Serum samples from 500 blood donors who donated blood at the Tehran Blood Transfusion Center were collected between May and October 2005. Serum samples were examined for IgM and IgG antibodies to West Nile virus using the ELISA method. The samples were tested for the presence of West Nile virus RNA by the real-time RT-polymerase chain reaction assay. All data were analyzed statistically using the Chi-Square test. All 500 donors were negative for West Nile virus-specific IgM antibody at the time of donation. No WNV RNA-positive samples were detected. The percentage of seropositivity of IgG antibodies to WNV was 5% at donation. No evidence of WNV-specific IgM antibody and WNV RNA in blood donor samples was found. In order to increase the safety of blood donation, it is essential to continue surveillance of this emerging infection in order to protect the blood supply in the future.

  18. West Nile Virus in Farmed Alligators

    PubMed Central

    Mauel, Michael J.; Baldwin, Charles; Burtle, Gary; Ingram, Dallas; Hines, Murray E.; Frazier, Kendal S.

    2003-01-01

    Seven alligators were submitted to the Tifton Veterinary Diagnostic and Investigational Laboratory for necropsy during two epizootics in the fall of 2001 and 2002. The alligators were raised in temperature-controlled buildings and fed a diet of horsemeat supplemented with vitamins and minerals. Histologic findings in the juvenile alligators were multiorgan necrosis, heterophilic granulomas, and heterophilic perivasculitis and were most indicative of septicemia or bacteremia. Histologic findings in a hatchling alligator were random foci of necrosis in multiple organs and mononuclear perivascular encephalitis, indicative of a viral cause. West Nile virus was isolated from submissions in 2002. Reverse transcription-polymerase chain reaction (RT-PCR) results on all submitted case samples were positive for West Nile virus for one of four cases associated with the 2001 epizootic and three of three cases associated with the 2002 epizootic. RT-PCR analysis was positive for West Nile virus in the horsemeat collected during the 2002 outbreak but negative in the horsemeat collected after the outbreak. PMID:12890319

  19. Usutu virus persistence and West Nile virus inactivity in the Emilia-Romagna region (Italy) in 2011.

    PubMed

    Calzolari, Mattia; Bonilauri, Paolo; Bellini, Romeo; Albieri, Alessandro; Defilippo, Francesco; Tamba, Marco; Tassinari, Massimo; Gelati, Antonio; Cordioli, Paolo; Angelini, Paola; Dottori, Michele

    2013-01-01

    The circulation of West Nile virus and Usutu virus was detected in the Emilia-Romagna region in 2008 and 2009. To evaluate the extent of circulation of both viruses, environmental surveillance, based on bird and mosquito testing, was conducted in 2008 and gradually improved over the years. In February-March 2009-2011, 5,993 hibernating mosquitoes were manually sampled, out of which 80.1% were Culex pipiens; none tested positive for the viruses. From 2008 to 2011, 946,213 mosquitoes, sampled between May and October, were tested; 86.5% were Cx. pipiens. West Nile virus was detected in 32 Cx. pipiens pools, and Usutu virus was detected in 229 mosquito pools (217 Cx. pipiens, 10 Aedes albopictus, one Anopheles maculipennis s.l., and one Aedes caspius). From 2009 to 2011, of 4,546 birds collected, 42 tested positive for West Nile virus and 48 for Usutu virus. West Nile virus and Usutu virus showed different patterns of activity during the 2008-2011 surveillance period. West Nile virus was detected in 2008, 2009, and 2010, but not in 2011. Usutu virus, however, was continuously active throughout 2009, 2010, and 2011. The data strongly suggest that both viruses overwinter in the surveyed area rather than being continually reintroduced every season. The lack of hibernating mosquitoes testing positive for the viruses and the presence of positive birds sampled early in the season support the hypothesis that the viruses overwinter in birds rather than in mosquitoes. Herd immunity in key bird species could explain the decline of West Nile virus observed in 2011, while the persistence of Usutu virus may be explained by not yet identified reservoirs. Reported results are comparable with a peri-Mediterranean circulation of the West Nile virus lineage 1 related strain, which became undetectable in the environment after two to three years of obvious circulation.

  20. Vaccines in development against West Nile virus.

    PubMed

    Brandler, Samantha; Tangy, Frederic

    2013-09-30

    West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

  1. Transmission of West Nile virus from an organ donor to four transplant recipients.

    PubMed

    Iwamoto, Martha; Jernigan, Daniel B; Guasch, Antonio; Trepka, Mary Jo; Blackmore, Carina G; Hellinger, Walter C; Pham, Si M; Zaki, Sherif; Lanciotti, Robert S; Lance-Parker, Susan E; DiazGranados, Carlos A; Winquist, Andrea G; Perlino, Carl A; Wiersma, Steven; Hillyer, Krista L; Goodman, Jesse L; Marfin, Anthony A; Chamberland, Mary E; Petersen, Lyle R

    2003-05-29

    In August 2002, fever and mental-status changes developed in recipients of organs from a common donor. Transmission of West Nile virus through organ transplantation was suspected. We reviewed medical records, conducted interviews, and collected blood and tissue samples for testing with a variety of assays. Persons who donated blood to the organ donor and associated blood components were identified and tested for West Nile virus. We identified West Nile virus infection in the organ donor and in all four organ recipients. Encephalitis developed in three of the organ recipients, and febrile illness developed in one. Three recipients became seropositive for West Nile virus IgM antibody; the fourth recipient had brain tissue that was positive for West Nile virus by isolation and nucleic acid and antigen assays. Serum specimens obtained from the organ donor before and immediately after blood transfusions showed no evidence of West Nile virus; however, serum and plasma samples obtained at the time of organ recovery were positive on viral nucleic acid testing and viral culture. The organ donor had received blood transfusions from 63 donors. A review of blood donors and follow-up testing identified one donor who had viremia at the time of donation and who became seropositive for West Nile virus IgM antibodies during the next two months. Our investigation of this cluster documents the transmission of West Nile virus by organ transplantation. Organ recipients receiving immunosuppressive drugs may be at high risk for severe disease after West Nile virus infection. Blood transfusion was the probable source of the West Nile virus viremia in the organ donor. Copyright 2003 Massachusetts Medical Society

  2. Phylogenetic analysis of West Nile virus, Nuevo Leon State, Mexico.

    PubMed

    Blitvich, Bradley J; Fernández-Salas, Ildefonso; Contreras-Cordero, Juan F; Loroño-Pino, María A; Marlenee, Nicole L; Díaz, Francisco J; González-Rojas, José I; Obregón-Martínez, Nelson; Chiu-García, Jorge A; Black, William C; Beaty, Barry J

    2004-07-01

    West Nile virus RNA was detected in brain tissue from a horse that died in June 2003 in Nuevo Leon State, Mexico. Nucleotide sequencing and phylogenetic analysis of the premembrane and envelope genes showed that the virus was most closely related to West Nile virus isolates collected in Texas in 2002.

  3. Vaccines in Development against West Nile Virus

    PubMed Central

    Brandler, Samantha; Tangy, Frederic

    2013-01-01

    West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine. PMID:24084235

  4. West Nile virus: a primer for the otolaryngologist.

    PubMed

    Michaelson, Peter G; Mair, Eric A

    2005-03-01

    Since recognition in the United States with a 1999 New York City epidemic, West Nile virus has enduringly migrated westward, leaving few states unaffected. Infection rates are rising at an alarming rate, doubling every year since introduction, with more than 9800 cases in 2003 alone and more than 260 deaths. Patients may present with myriad symptoms including a maculopapular rash that affects the face and trunk and diffuse lymphadenopathy, both of which may result in the initial consultation of the otolaryngologist. We review the clinical history of West Nile virus and its epidemiology, laboratory findings, and variable clinical presentation, with an emphasis on otolaryngologic manifestations. STUDY DESIGN AND SETTING COMPREHENSIVE: review of the literature over the past 50 years with an emphasis on what the present-day otolaryngologist needs to know concerning West Nile virus. Clinical manifestations of the head and neck such as encephalitis, meningitis, maculopapular rash, lymphadenopathy and dysphagia are discussed. To date, there are no articles in the otolaryngology literature discussing West Nile virus. These patients may present initially to multiple providers in diverse specialties because of multifarious initial signs and symptoms. The otolaryngologist must be educated on this quickly growing affliction and practice with a high index of suspicion. In this article we describe the clinical manifestations of West Nile virus, with an emphasis on the otolaryngologic manifestations. The otolaryngologist must become educated about this entity to facilitate preventative measures, adequately treat, and assist other providers in hopeful control and potential eradication of this infectious threat.

  5. Phylogenetic Analysis of West Nile Virus, Nuevo Leon State, Mexico

    PubMed Central

    Blitvich, Bradley J.; Fernández-Salas, Ildefonso; Contreras-Cordero, Juan F.; Loroño-Pino, María A.; Marlenee, Nicole L.; Díaz, Francisco J.; González-Rojas, José I.; Obregón-Martínez, Nelson; Chiu-García, Jorge A.; Black, William C.

    2004-01-01

    West Nile virus RNA was detected in brain tissue from a horse that died in June 2003 in Nuevo Leon State, Mexico. Nucleotide sequencing and phylogenetic analysis of the premembrane and envelope genes showed that the virus was most closely related to West Nile virus isolates collected in Texas in 2002. PMID:15324558

  6. [West Nile virus transmission risk in the Czech Republic].

    PubMed

    Vlčková, J; Rupeš, V; Horáková, D; Kollárová, H; Holý, O

    2015-06-01

    West Nile Virus (WNV) belongs to the family Flaviviridae. It is transmitted to humans by mosquitoes, capable of sucking blood on birds and mammals, most often by mosquitoes of the genus Culex. In humans, the virus was first identified in 1937 in the West Nile region, Uganda, Africa. Later, the virus spread and caused more or less severe epidemics of West Nile fever in North Africa, Europe, Asia, and North and South America. During the last two decades, WNV has been on the rise and is currently ranked as one of the most prevalent arboviruses in the world. In humans, WNV infection mostly occurs as asymptomatic, but may have a more severe or even fatal course in older and weakened patients. Humans may become infected not only by mosquitoes that acquire the virus from infected birds, but also through a blood transfusion, organ transplant, breast milk and transplacental transmission, or contact with infected animals, their blood, and tissues. The first autochthonous human case of West Nile fever in the Czech Republic was reported from South Moravia in 1997. In 2013, another case of West Nile fever emerged in this country, in the Ostrava area. The issue of WNV has recently been studied from many different perspectives, as evidenced by many original and review papers. This article briefly reviews the essential knowledge about this virus and its spread.

  7. Identifying the environmental conditions favouring West Nile Virus outbreaks in Europe.

    PubMed

    Marcantonio, Matteo; Rizzoli, Annapaola; Metz, Markus; Rosà, Roberto; Marini, Giovanni; Chadwick, Elizabeth; Neteler, Markus

    2015-01-01

    West Nile Virus (WNV) is a globally important mosquito borne virus, with significant implications for human and animal health. The emergence and spread of new lineages, and increased pathogenicity, is the cause of escalating public health concern. Pinpointing the environmental conditions that favour WNV circulation and transmission to humans is challenging, due both to the complexity of its biological cycle, and the under-diagnosis and reporting of epidemiological data. Here, we used remote sensing and GIS to enable collation of multiple types of environmental data over a continental spatial scale, in order to model annual West Nile Fever (WNF) incidence across Europe and neighbouring countries. Multi-model selection and inference were used to gain a consensus from multiple linear mixed models. Climate and landscape were key predictors of WNF outbreaks (specifically, high precipitation in late winter/early spring, high summer temperatures, summer drought, occurrence of irrigated croplands and highly fragmented forests). Identification of the environmental conditions associated with WNF outbreaks is key to enabling public health bodies to properly focus surveillance and mitigation of West Nile virus impact, but more work needs to be done to enable accurate predictions of WNF risk.

  8. The natural history of West Nile virus infection presenting with West Nile virus meningoencephalitis in a man with a prolonged illness: a case report.

    PubMed

    Mainali, Shraddha; Afshani, Mansoor; Wood, James B; Levin, Michael C

    2011-05-25

    Estimates indicate that West Nile virus infects approximately one and a half million people in the United States of America. Up to 1% may develop West Nile virus neuroinvasive disease, in which infected patients develop any combination of meningitis, encephalitis, or acute paralysis. A 56-year-old African-American man presented to our hospital with headache, restlessness, fever, myalgias, decreased appetite, and progressive confusion. A cerebrospinal fluid examination showed mild leukocytosis and an elevated protein level. Testing for routine infections was negative. Brain T2-weighted magnetic resonance imaging scans showed marked enlargement of caudate nuclei and increased intensity within the basal ganglia and thalami. A West Nile virus titer was positive, and serial brain magnetic resonance imaging scans showed resolving abnormalities that paralleled his neurological examination. This report is unusual as it portrays the natural history and long-term consequences of West Nile virus meningoencephalitis diagnosed on the basis of serial brain images.

  9. Recent progress in West Nile virus diagnosis and vaccination

    PubMed Central

    2012-01-01

    West Nile virus (WNV) is a positive-stranded RNA virus belonging to the Flaviviridae family, a large family with 3 main genera (flavivirus, hepacivirus and pestivirus). Among these viruses, there are several globally relevant human pathogens including the mosquito-borne dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV) and West Nile virus (WNV), as well as tick-borne viruses such as tick-borne encephalitis virus (TBEV). Since the mid-1990s, outbreaks of WN fever and encephalitis have occurred throughout the world and WNV is now endemic in Africa, Asia, Australia, the Middle East, Europe and the Unites States. This review describes the molecular virology, epidemiology, pathogenesis, and highlights recent progress regarding diagnosis and vaccination against WNV infections. PMID:22380523

  10. Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kanai,R.; Kar, K.; Anthony, K.

    2006-01-01

    West Nile virus, a member of the Flavivirus genus, causes fever that can progress to life-threatening encephalitis. The major envelope glycoprotein, E, of these viruses mediates viral attachment and entry by membrane fusion. We have determined the crystal structure of a soluble fragment of West Nile virus E. The structure adopts the same overall fold as that of the E proteins from dengue and tick-borne encephalitis viruses. The conformation of domain II is different from that in other prefusion E structures, however, and resembles the conformation of domain II in postfusion E structures. The epitopes of neutralizing West Nile virus-specificmore » antibodies map to a region of domain III that is exposed on the viral surface and has been implicated in receptor binding. In contrast, we show that certain recombinant therapeutic antibodies, which cross-neutralize West Nile and dengue viruses, bind a peptide from domain I that is exposed only during the membrane fusion transition. By revealing the details of the molecular landscape of the West Nile virus surface, our structure will assist the design of antiviral vaccines and therapeutics.« less

  11. The first human case of neuroinvasive West Nile virus infection identified in Cyprus.

    PubMed

    Paphitou, Niki I; Tourvas, Aristomenis; Floridou, Dora; Richter, Jan; Tryfonos, Christina; Christodoulou, Christina

    West Nile virus infection can pose a diagnostic challenge to clinicians, especially in geographic areas where human cases of this disease have never been encountered before. In August 2016, the first human case of West Nile virus infection was diagnosed in Cyprus. An elderly non immunosuppressed patient with a history of recent travel, presented with a clinical picture of rapidly progressing ascending paralysis mimicking Guillain-Barré syndrome. Neuroinvasive West Nile virus disease was diagnosed by detecting West Nile virus nucleic acid in the patient's cerebrospinal fluid. Public health measures were taken raising awareness regarding this disease and its prevention. Clinical vigilance to consider West Nile virus as a possible emerging pathogen in the appropriate clinical setting is warranted and could benefit individual patients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Predictable ecology and geography of West Nile virus transmission in the central United States.

    PubMed

    Peterson, A Townsend; Robbins, Amber; Restifo, Robert; Howell, James; Nasci, Roger

    2008-12-01

    West Nile virus (WNV) arrived in North America and spread rapidly through the western hemisphere. We present a series of tests to determine whether ecological factors are consistently associated with WNV transmission to humans. We analyzed human WNV cases in the states of Illinois, Indiana, and Ohio in 2002 and 2003, building ecological niche models to associate WNV case occurrences with ecological and environmental parameters. In essentially all tests, both within states, among states, between years, and across the region, we found high predictivity of WNV case distributions, suggesting that one or more elements in the WNV transmission cycle has a strong ecological determination. Areas in the geographic region included in this study predicted as suitable for WNV transmission tended to have lower values of the vegetation indices in the summer months, pointing to consistent ecological differences between suitable and unsuitable areas.

  13. The use of early summer mosquito surveillance to predict late summer West Nile virus activity

    USGS Publications Warehouse

    Ginsberg, Howard S.; Rochlin, Ilia; Campbell, Scott R.

    2010-01-01

    Utility of early-season mosquito surveillance to predict West Nile virus activity in late summer was assessed in Suffolk County, NY. Dry ice-baited CDC miniature light traps paired with gravid traps were set weekly. Maximum-likelihood estimates of WNV positivity, minimum infection rates, and % positive pools were generally well correlated. However, positivity in gravid traps was not correlated with positivity in CDC light traps. The best early-season predictors of WNV activity in late summer (estimated using maximum-likelihood estimates of Culex positivity in August and September) were early date of first positive pool, low numbers of mosquitoes in July, and low numbers of mosquito species in July. These results suggest that early-season entomological samples can be used to predict WNV activity later in the summer, when most human cases are acquired. Additional research is needed to establish which surveillance variables are most predictive and to characterize the reliability of the predictions.

  14. West Nile virus: Uganda, 1937, to New York City, 1999.

    PubMed

    Hayes, C G

    2001-12-01

    West Nile virus, first isolated in 1937, is among the earliest arthropod-borne viruses discovered by humans. Its broad geographical distribution, not uncommon infection of humans, transmission by mosquitoes, and association with wild birds as enzootic hosts were well documented by the mid-1960s. However, West Nile virus was not considered to be a significant human pathogen because most infections appeared to result in asymptomatic or only mild febrile disease. Several epidemics had been documented prior to 1996, some involving hundreds to thousands of cases in mostly rural populations, but only a few cases of severe neurological disease had been reported. The occurrence between 1996 and 1999 of three major epidemics, in southern Romania, the Volga delta in southern Russia, and the northeastern United States, involving hundreds of cases of severe neurological disease and fatal infections was totally unexpected. These were the first epidemics reported in large urban populations. A significant factor that appeared in common to all three outbreaks was the apparent involvement of the common house mosquito, Culex pipiens, as a vector. This species had not previously been implicated as important in the transmission of West Nile virus. In addition the epidemic in the northeastern United States was unusual in the association of West Nile virus infection with fatal disease of birds, suggesting a change in the virulence of the virus toward this host. Understanding the risk factors that contributed to these three urban epidemics is important for minimizing the potential for future occurrences. This review will attempt to compare observations on the biology of West Nile virus made over about 60 years prior to the recent epidemics to observations made in association with these urban epidemics.

  15. Purpura fulminans associated with acute West Nile virus encephalitis.

    PubMed

    Shah, Sheevam; Fite, Laura Paul; Lane, Natalie; Parekh, Palak

    2016-02-01

    Purpura fulminans is a progressive thrombotic disorder that presents with widespread purpura due to deficiency or dysfunction of protein C or protein S. Lesions present as well-demarcated erythematous macules that progress to irregular areas of hemorrhagic necrosis.West Nile virus is a member of the Flaviviridae family transmitted to humans through the bite of various mosquito species. It manifests as West Nile fever in 25% of those infected and less commonly as neuroinvasive disease. An African American man in his fortiespresented with altered mental status and was noted to have evidence of disseminated intravascular coagulation according to his lab data. He then developed dusky skin discoloration and systemic flaccid bullae with desquamation. Biopsy was consistent with purpura fulminans and the patient eventually developed symmetric peripheral gangrene, requiring amputations of all four extremities. Infectious work up revealed positive testing for IgM and IgG antibodies in serum and cerebrospinal fluid leading to the diagnosis of acute West Nile Virus encephalitis. We present this case to describe the rarely reported association of purpura fulminans with West Nile Virus infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. West Nile Virus: Biology, Transmission, and Human Infection

    PubMed Central

    Colpitts, Tonya M.; Conway, Michael J.; Montgomery, Ruth R.

    2012-01-01

    Summary: West Nile Virus was introduced into the Western Hemisphere during the late summer of 1999 and has been causing significant and sometimes severe human diseases since that time. This article briefly touches upon the biology of the virus and provides a comprehensive review regarding recent discoveries about virus transmission, virus acquisition, and human infection and disease. PMID:23034323

  17. Geospatial Analysis and Seasonal Distribution of West Nile Virus Vectors (Diptera: Culicidae) in Southern Ontario, Canada

    PubMed Central

    Turner, Kevin W.; Hunter, Fiona F.

    2018-01-01

    The purpose of this study was to establish geospatial and seasonal distributions of West Nile virus vectors in southern Ontario, Canada using historical surveillance data from 2002 to 2014. We set out to produce mosquito abundance prediction surfaces for each of Ontario’s thirteen West Nile virus vectors. We also set out to determine whether elevation and proximity to conservation areas and provincial parks, wetlands, and population centres could be used to improve our model. Our results indicated that the data sets for Anopheles quadrimaculatus, Anopheles punctipennis, Anopheles walkeri, Culex salinarius, Culex tarsalis, Ochlerotatus stimulans, and Ochlerotatus triseriatus were not suitable for geospatial modelling because they are randomly distributed throughout Ontario. Spatial prediction surfaces were created for Aedes japonicus and proximity to wetlands, Aedes vexans and proximity to population centres, Culex pipiens/restuans and proximity to population centres, Ochlerotatus canadensis and elevation, and Ochlerotatus trivittatus and proximity to population centres using kriging. Seasonal distributions are presented for all thirteen species. We have identified both when and where vector species are most abundant in southern Ontario. These data have the potential to contribute to a more efficient and focused larvicide program and West Nile virus awareness campaigns. PMID:29597256

  18. A review of vaccine approaches for West Nile virus.

    PubMed

    Iyer, Arun V; Kousoulas, Konstantin G

    2013-09-10

    The West Nile virus (WNC) first appeared in North America in 1999. The North American lineages of WNV were characterized by the presence of neuroinvasive and neurovirulent strains causing disease and death in humans, birds and horses. The 2012 WNV season in the United States saw a massive spike in the number of neuroinvasive cases and deaths similar to what was seen in the 2002-2003 season, according to the West Nile virus disease cases and deaths reported to the CDC by year and clinical presentation, 1999-2012, by ArboNET (Arboviral Diseases Branch, Centers for Disease Control and Prevention). In addition, the establishment and recent spread of lineage II WNV virus strains into Western Europe and the presence of neurovirulent and neuroinvasive strains among them is a cause of major concern. This review discusses the advances in the development of vaccines and biologicals to combat human and veterinary West Nile disease.

  19. A Review of Vaccine Approaches for West Nile Virus

    PubMed Central

    Iyer, Arun V.; Kousoulas, Konstantin G.

    2013-01-01

    The West Nile virus (WNC) first appeared in North America in 1999. The North American lineages of WNV were characterized by the presence of neuroinvasive and neurovirulent strains causing disease and death in humans, birds and horses. The 2012 WNV season in the United States saw a massive spike in the number of neuroinvasive cases and deaths similar to what was seen in the 2002–2003 season, according to the West Nile virus disease cases and deaths reported to the CDC by year and clinical presentation, 1999–2012, by ArboNET (Arboviral Diseases Branch, Centers for Disease Control and Prevention). In addition, the establishment and recent spread of lineage II WNV virus strains into Western Europe and the presence of neurovirulent and neuroinvasive strains among them is a cause of major concern. This review discusses the advances in the development of vaccines and biologicals to combat human and veterinary West Nile disease. PMID:24025396

  20. 78 FR 16505 - Prospective Grant of Exclusive License: Chimeric West Nile/Dengue Viruses

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-15

    ... Grant of Exclusive License: Chimeric West Nile/Dengue Viruses AGENCY: Centers for Disease Control and... giving an exclusive license, in the field of use of in vitro diagnostics for dengue virus infection, to.... Provisional Application 61/049,342, filed 4/30/2008, entitled ``Engineered, Chimeric West Nile/Dengue Viruses...

  1. Predictive risk mapping of West Nile virus (WNV) infection in Saskatchewan horses.

    PubMed

    Epp, Tasha Y; Waldner, Cheryl; Berke, Olaf

    2011-07-01

    The objective of this study was to develop a model using equine data from geographically limited surveillance locations to predict risk categories for West Nile virus (WNV) infection in horses in all geographic locations across the province of Saskatchewan. The province was divided geographically into low-, medium-, or high-risk categories for WNV, based on available serology information from 923 horses obtained through 4 studies of WNV infection in horse populations in Saskatchewan. Discriminant analysis was used to build models using the observed risk of WNV in horses and geographic division-specific environmental data as well as to predict the risk category for all areas, including those beyond the surveillance zones. High-risk areas were indicated by relatively lower rainfall, higher temperatures, and a lower percentage of area covered in trees, water, and wetland. These conditions were most often identified in the southwest corner of the province. Environmental conditions can be used to identify those areas that are at highest risk for WNV. Public health managers could use prediction maps, which are based on animal or human information and developed from annual early season meteorological information, to guide ongoing decisions about when and where to focus intervention strategies for WNV.

  2. West Nile Virus Infection among Humans, Texas, USA, 2002–2011

    PubMed Central

    Nolan, Melissa S.; Schuermann, Jim

    2013-01-01

    We conducted an epidemiologic analysis to document West Nile virus infections among humans in Texas, USA, during 2002–2011. West Nile virus has become endemic to Texas; the number of reported cases increased every 3 years. Risk for infection was greatest in rural northwestern Texas, where Culex tarsalis mosquitoes are the predominant mosquito species. PMID:23260575

  3. Inhibitors of Dengue virus and West Nile virus proteases based on the aminobenzamide scaffold.

    PubMed

    Aravapalli, Sridhar; Lai, Huiguo; Teramoto, Tadahisa; Alliston, Kevin R; Lushington, Gerald H; Ferguson, Eron L; Padmanabhan, R; Groutas, William C

    2012-07-01

    Dengue and West Nile viruses (WNV) are mosquito-borne members of flaviviruses that cause significant morbidity and mortality. There is no approved vaccine or antiviral drugs for human use to date. In this study, a series of functionalized meta and para aminobenzamide derivatives were synthesized and subsequently screened in vitro against Dengue virus and West Nile virus proteases. Four active compounds were identified which showed comparable activity toward the two proteases and shared in common a meta or para(phenoxy)phenyl group. The inhibition constants (K(i)) for the most potent compound 7n against Dengue and West Nile virus proteases were 8.77 and 5.55 μM, respectively. The kinetics data support a competitive mode of inhibition of both proteases by compound 7n. This conclusion is further supported by molecular modeling. This study reveals a new chemical scaffold which is amenable to further optimization to yield potent inhibitors of the viral proteases via the combined utilization of iterative medicinal chemistry/structure-activity relationship studies and in vitro screening. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Actin filaments participate in West Nile (Sarafend) virus maturation process.

    PubMed

    Chu, J J H; Choo, B G H; Lee, J W M; Ng, M L

    2003-11-01

    West Nile (Sarafend) virus has previously been shown to egress by budding at the plasma membrane of infected cells, but relatively little is known about the mechanism involved in this mode of release. During the course of this study, it was discovered that actin filaments take part in the virus maturation process. Using dual-labeled immunofluorescence and immunoelectron microscopy at late infection (10 hr p.i.), co-localization of viral structural (envelope and capsid) proteins with actin filaments was confirmed. The virus structural proteins were also immunoprecipitated with anti-actin antibody, further demonstrating the strong association between the two components. Perturbation of actin filaments by cytochalasin B strongly inhibited the release of West Nile virus (approximately 10,000-fold inhibition) when compared with the untreated cells. Infectious virus particles were recovered after the removal of cytochalasin B. Further confirmation was obtained when nucleocapsid particles were found associated with disrupted actin filaments at the periphery of cytochalasin B-treated cells. Together, these results showed that actin filaments do indeed have a key role in the release of West Nile (Sarafend) virions. Copyright 2003 Wiley-Liss, Inc.

  5. Analysis of YouTube as a Source of Information for West Nile Virus Infection

    PubMed Central

    Dubey, Divyanshu; Amritphale, Amod; Sawhney, Anshudha; Dubey, Devashish; Srivastav, Nupur

    2014-01-01

    Introduction A major outbreak of West Nile Virus was seen last year in different parts of the United States. Adequate dissemination of correct information about the disease would have helped decrease its spread and the associated panic in the general population. In this study, we looked into the use of YouTube as a resource for providing information about West Nile Virus infection. Objective This study aims to identify and evaluate YouTube as resource for providing information on West Nile Virus infection to the general public. Methods YouTube was searched on November 25, 2012, using the keywords West Nile Virus epidemic, West Nile Virus infection, and West Nile Virus prevention for videos uploaded in the past 6 months containing relevant information about the disease. The videos were classified as useful, misleading, or as news updates based on the type of information contained. Total viewership, number of days since upload, total duration of videos, and source of upload were noted. Results A total of 106 videos with information on West Nile Virus infection were included in the study, with 79.24% having useful information about the disease. Among the useful videos, 51/84 (60.71%) had information on disease prevention, and 29/84 (34.52%) contained information on news and research updates. The majority of these videos were uploaded by individuals (54.6%) or news agencies (41.8 %). Healthcare agencies contributed only 3.4 % of the total videos. Even though the useful videos represented 72% of all videos, there was significantly higher total viewership and viewership per day for the non-useful videos (P<0.05). Conclusions YouTube may be a significant resource for dissemination of information on public health issues like West Nile virus infection and should be targeted by healthcare agencies for this use. The major drawback of this medium is lack of verification by authorized healthcare professionals before these videos are made available for viewing by the community

  6. Analysis of YouTube as a source of information for West Nile Virus infection.

    PubMed

    Dubey, Divyanshu; Amritphale, Amod; Sawhney, Anshudha; Dubey, Devashish; Srivastav, Nupur

    2014-12-01

    A major outbreak of West Nile Virus was seen last year in different parts of the United States. Adequate dissemination of correct information about the disease would have helped decrease its spread and the associated panic in the general population. In this study, we looked into the use of YouTube as a resource for providing information about West Nile Virus infection. This study aims to identify and evaluate YouTube as resource for providing information on West Nile Virus infection to the general public. YouTube was searched on November 25, 2012, using the keywords West Nile Virus epidemic, West Nile Virus infection, and West Nile Virus prevention for videos uploaded in the past 6 months containing relevant information about the disease. The videos were classified as useful, misleading, or as news updates based on the type of information contained. Total viewership, number of days since upload, total duration of videos, and source of upload were noted. A total of 106 videos with information on West Nile Virus infection were included in the study, with 79.24% having useful information about the disease. Among the useful videos, 51/84 (60.71%) had information on disease prevention, and 29/84 (34.52%) contained information on news and research updates. The majority of these videos were uploaded by individuals (54.6%) or news agencies (41.8 %). Healthcare agencies contributed only 3.4 % of the total videos. Even though the useful videos represented 72% of all videos, there was significantly higher total viewership and viewership per day for the non-useful videos (P<0.05). YouTube may be a significant resource for dissemination of information on public health issues like West Nile virus infection and should be targeted by healthcare agencies for this use. The major drawback of this medium is lack of verification by authorized healthcare professionals before these videos are made available for viewing by the community. Hence, a strict caution should be exercised in

  7. West Nile virus infection.

    PubMed

    Guharoy, Roy; Gilroy, Shelley A; Noviasky, John A; Ference, Jonathan

    2004-06-15

    The epidemiology, virology, and transmission of West Nile virus (WNV) are reviewed, and the clinical features, diagnosis, and treatment of WNV infection are examined. WNV infection is caused by a flavivirus transmitted from birds to humans through the bite of culicine mosquitoes. WNV was discovered in the blood of a febrile woman from Uganda's West Nile province in 1937. The first case of domestically acquired WNV infection was reported in the United States in 1999 in New York. Since then, WNV infection has spread rapidly across the United States, with 9306 confirmed cases and 210 deaths reported from 45 states in 2003. It is still not clear how WNV was introduced into North America. WNV is a small, single-stranded RNA virus and a member of the Japanese encephalitis virus antigenic complex. While most humans infected with WNV are asymptomatic, some may develop an influenza-like illness. Disease surveillance remains the cornerstone for the early recognition and control of WNV. We describe one case of WNV infection with an update on the disease. Strategies for the prevention and control of this infection are reviewed. There is no established treatment for WNV infection. Currently, prevention and control are the only measures that help decrease the morbidity and mortality associated with WNV infection. As the number of cases escalates and the geographic distribution of WNV infection widens, the epidemic will continue to pose a major challenge to clinicians in the coming years. There is an urgent need for more research on the pathogenesis and treatment of WNV infection.

  8. European Surveillance for West Nile Virus in Mosquito Populations

    PubMed Central

    Engler, Olivier; Savini, Giovanni; Papa, Anna; Figuerola, Jordi; Groschup, Martin H.; Kampen, Helge; Medlock, Jolyon; Vaux, Alexander; Wilson, Anthony J.; Werner, Doreen; Jöst, Hanna; Goffredo, Maria; Capelli, Gioia; Federici, Valentina; Tonolla, Mauro; Patocchi, Nicola; Flacio, Eleonora; Portmann, Jasmine; Rossi-Pedruzzi, Anya; Mourelatos, Spiros; Ruiz, Santiago; Vázquez, Ana; Calzolari, Mattia; Bonilauri, Paolo; Dottori, Michele; Schaffner, Francis; Mathis, Alexander; Johnson, Nicholas

    2013-01-01

    A wide range of arthropod-borne viruses threaten both human and animal health either through their presence in Europe or through risk of introduction. Prominent among these is West Nile virus (WNV), primarily an avian virus, which has caused multiple outbreaks associated with human and equine mortality. Endemic outbreaks of West Nile fever have been reported in Italy, Greece, France, Romania, Hungary, Russia and Spain, with further spread expected. Most outbreaks in Western Europe have been due to infection with WNV Lineage 1. In Eastern Europe WNV Lineage 2 has been responsible for human and bird mortality, particularly in Greece, which has experienced extensive outbreaks over three consecutive years. Italy has experienced co-circulation with both virus lineages. The ability to manage this threat in a cost-effective way is dependent on early detection. Targeted surveillance for pathogens within mosquito populations offers the ability to detect viruses prior to their emergence in livestock, equine species or human populations. In addition, it can establish a baseline of mosquito-borne virus activity and allow monitoring of change to this over time. Early detection offers the opportunity to raise disease awareness, initiate vector control and preventative vaccination, now available for horses, and encourage personal protection against mosquito bites. This would have major benefits through financial savings and reduction in equid morbidity/mortality. However, effective surveillance that predicts virus outbreaks is challenged by a range of factors including limited resources, variation in mosquito capture rates (too few or too many), difficulties in mosquito identification, often reliant on specialist entomologists, and the sensitive, rapid detection of viruses in mosquito pools. Surveillance for WNV and other arboviruses within mosquito populations varies between European countries in the extent and focus of the surveillance. This study reviews the current status of

  9. Alexander the Great and West Nile virus encephalitis.

    PubMed

    Marr, John S; Calisher, Charles H

    2003-12-01

    Alexander the Great died in Babylon in 323 BC. His death at age 32 followed a 2-week febrile illness. Speculated causes of death have included poisoning; assassination, and a number of infectious diseases. One incident, mentioned by Plutarch but not considered by previous investigators, may shed light on the cause of Alexander's death. The incident, which occurred as he entered Babylon, involved a flock of ravens exhibiting unusual behavior and subsequently dying at his feet. The inexplicable behavior of ravens is reminiscent of avian illness and death weeks before the first human cases of West Nile virus infection were identified in the United States. We posit that Alexander may have died of West Nile virus encephalitis.

  10. Stress hormones predict a host superspreader phenotype in the West Nile virus system

    USGS Publications Warehouse

    Gervasi, Stephanie; Burgan, Sarah; Hofmeister, Erik K.; Unnasch, Thomas R.; Martin, Lynn B.

    2017-01-01

    Glucocorticoid stress hormones, such as corticosterone (CORT), have profound effects on the behaviour and physiology of organisms, and thus have the potential to alter host competence and the contributions of individuals to population- and community-level pathogen dynamics. For example, CORT could alter the rate of contacts among hosts, pathogens and vectors through its widespread effects on host metabolism and activity levels. CORT could also affect the intensity and duration of pathogen shedding and risk of host mortality during infection. We experimentally manipulated songbird CORT, asking how CORT affected behavioural and physiological responses to a standardized West Nile virus (WNV) challenge. Although all birds became infected after exposure to the virus, only birds with elevated CORT had viral loads at or above the infectious threshold. Moreover, though the rate of mortality was faster in birds with elevated CORT compared with controls, most hosts with elevated CORT survived past the day of peak infectiousness. CORT concentrations just prior to inoculation with WNV and anti-inflammatory cytokine concentrations following viral exposure were predictive of individual duration of infectiousness and the ability to maintain physical performance during infection (i.e. tolerance), revealing putative biomarkers of competence. Collectively, our results suggest that glucocorticoid stress hormones could directly and indirectly mediate the spread of pathogens.

  11. Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    D’Arcy, Allan, E-mail: allan.darcy@novartis.com; Chaillet, Maxime; Schiering, Nikolaus

    Crystals of dengue serotype 2 and West Nile virus NS2B–NS3 protease complexes have been obtained and the crystals of both diffract to useful resolution. Sample homogeneity was essential for obtaining X-ray-quality crystals of the dengue protease. Controlled proteolysis produced a crystallizable fragment of the apo West Nile virus NS2B–NS3 and crystals were also obtained in the presence of a peptidic inhibitor. Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but maymore » also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B–NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained.« less

  12. Neuropsychological Impact of West Nile Virus Infection: An Extensive Neuropsychiatric Assessment of 49 Cases in Canada.

    PubMed

    Samaan, Zainab; McDermid Vaz, Stephanie; Bawor, Monica; Potter, Tammy Hlywka; Eskandarian, Sasha; Loeb, Mark

    2016-01-01

    West Nile virus emerged as an important human pathogen in North America and continues to pose a risk to public health. It can cause a highly variable range of clinical manifestations ranging from asymptomatic to severe illness. Neuroinvasive disease due to West Nile virus can lead to long-term neurological deficits and psychological impairment. However, these deficits have not been well described. The objective of this study was to characterize the neuropsychological manifestations of West Nile virus infection with a focus on neuroinvasive status and time since infection. Patients from Ontario Canada with a diagnosis of neuroinvasive disease (meningitis, encephalitis, or acute flaccid paralysis) and non-neuroinvasive disease who had participated in a cohort study were enrolled. Clinical and laboratory were collected, as well as demographics and medical history. Cognitive functioning was assessed using a comprehensive battery of neuropsychological tests. Data from 49 individuals (32 with West Nile fever and 17 with West Nile neuroinvasive disease) were included in the present cross-sectional analysis. Patterns of neuropsychological impairment were comparable across participants with both neuroinvasive and non-neuroinvasive West Nile virus infection on all cognitive measures. Neuropsychiatric impairment was also observed more frequently at two to four years post-infection compared to earlier stages of illness. Our data provide objective evidence for cognitive difficulties among patients who were infected with West Nile virus; these deficits appear to manifest regardless of severity of West Nile virus infection (West Nile fever vs. West Nile neuroinvasive disease), and are more prevalent with increasing illness duration (2-4 years vs. 1 month). Data from this study will help inform patients and healthcare providers about the expected course of recovery, as well as the need to implement effective treatment strategies that include neuropsychological interventions.

  13. West nile virus in the United States - a historical perspective.

    PubMed

    Roehrig, John T

    2013-12-10

    Prior to 1999, West Nile virus (WNV) was a bit player in the screenplay of global vector-borne viral diseases. First discovered in the West Nile District of Uganda in 1937, this Culex sp.-transmitted virus was known for causing small human febrile outbreaks in Africa and the Middle East. Prior to 1995, the last major human WNV outbreak was in the 1950s in Israel. The epidemiology and ecology of WNV began to change in the mid-1990s when an epidemic of human encephalitis occurred in Romania. The introduction of WNV into Eastern Europe was readily explained by bird migration between Africa and Europe. The movement of WNV from Africa to Europe could not, however, predict its surprising jump across the Atlantic Ocean to New York City and the surrounding areas of the United States (U.S.). This movement of WNV from the Eastern to Western Hemisphere in 1999, and its subsequent dissemination throughout two continents in less than ten years is widely recognized as one of the most significant events in arbovirology during the last two centuries. This paper documents the early events of the introduction into and the spread of WNV in the Western Hemisphere.

  14. Clinical and pathologic features of West Nile virus infection in native North American owls (Family strigidae).

    PubMed

    Fitzgerald, S D; Patterson, J S; Kiupel, M; Simmons, H A; Grimes, S D; Sarver, C F; Fulton, R M; Steficek, B A; Cooley, T M; Massey, J P; Sikarskie, J G

    2003-01-01

    Since the initial report of West Nile virus in the northeastern United States in 1999, the virus has spread rapidly westward and southward across the country. In the summer of 2002, several midwestern states reported increased cases of neurologic disease and mortality associated with West Nile virus infection in various native North American owl species. This report summarizes the clinical and pathologic findings for 13 captive and free-ranging owls. Affected species were all in the family Strigidae and included seven snowy owls (Nyctea scandiaca), four great-horned owls (Bubo virginianus), a barred owl (Strix varia), and a short-eared owl (Asio flammeus). Neurologic signs identified included head tilt, uncoordinated flight, paralysis, tremors, and seizures. Owls that died were screened for flaviviral proteins by immunohistochemical staining of formalin-fixed tissues, followed by specific polymerase chain reaction assay to confirm West Nile virus with fresh tissues when available. Microscopic lesions were widespread, involving brain, heart, liver, kidney, and spleen, and were typically nonsuppurative with infiltration by predominantly lymphocytes and plasma cells. Lesions in owls were much more severe than those previously reported in corvids such as crows, which are considered highly susceptible to infection and are routinely used as sentinel species for monitoring for the presence and spread of West Nile virus. This report is the first detailed description of the pathology of West Nile virus infection in Strigiformes and indicates that this bird family is susceptible to natural infection with West Nile virus.

  15. DNA Vaccine for West Nile Virus Infection in Fish Crows (Corvus ossifragus)

    DTIC Science & Technology

    2003-09-01

    SUBJECT TERMS west Nile virus, vaccine , efficacy , crows 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT SAR 18. NUMBER OF PAGES 5 19a...A DNA vaccine for West Nile virus (WNV) was evaluat- ed to determine whether its use could protect fish crows (Corvus ossifragus) from fatal WNV...infection. Captured adult crows were given 0.5 mg of the DNA vaccine either orally or by intramuscular (IM) inoculation; control crows were inoculated or

  16. Purification and crystallization of dengue and West Nile virus NS2B-NS3 complexes.

    PubMed

    D'Arcy, Allan; Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic; Lim, Siew Pheng; Lefeuvre, Peggy; Erbel, Paul

    2006-02-01

    Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B-NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained.

  17. The Role of Innate Immunity in Conditioning Mosquito Susceptibility to West Nile Virus

    PubMed Central

    Prasad, Abhishek N.; Brackney, Doug. E.; Ebel, Gregory D.

    2013-01-01

    Arthropod-borne viruses (arboviruses) represent an emerging threat to human and livestock health globally. In particular, those transmitted by mosquitoes present the greatest challenges to disease control efforts. An understanding of the molecular basis for mosquito innate immunity to arbovirus infection is therefore critical to investigations regarding arbovirus evolution, virus-vector ecology, and mosquito vector competence. In this review, we discuss the current state of understanding regarding mosquito innate immunity to West Nile virus. We draw from the literature with respect to other virus-vector pairings to attempt to draw inferences to gaps in our knowledge about West Nile virus and relevant vectors. PMID:24351797

  18. West Nile virus in Canada: ever-changing, but here to stay.

    PubMed

    Zheng, H; Drebot, M A; Coulthart, M B

    2014-05-15

    The incidence of West Nile virus (WNv) has waxed and waned in Canada over the past 12 years, but it is unlikely to disappear. Climate change models, which suggest warming temperatures and changing patterns of precipitation, predict an expansion of geographic range for WNv in some regions of Canada, such as the Prairie provinces. Such projected changes in WNv distribution might also be accompanied by genetic changes in the virus and/or the range of bird and insect host species it infects. To address this risk, emphasis should be placed on preventing exposure to infected mosquitoes, conducting high-quality surveillance of WNv and WNv disease, controlling mosquito vectors, and promoting public and professional education.

  19. Ecology of West Nile Virus in North America

    PubMed Central

    Reisen, William K.

    2013-01-01

    The introduction, dispersal and establishment of West Nile virus in North America were reviewed, focusing on factors that may have enhanced receptivity and enabled the invasion process. The overwintering persistence of this tropical virus within temperate latitudes was unexpected, but was key in the transition from invasion to endemic establishment. The cascade of temporal events allowing sporadic amplification to outbreak levels was discussed within a future perspective. PMID:24008376

  20. Evaluating the Use of Commercial West Nile Virus Antigens as Positive Controls in the Rapid Analyte Measurement Platform West Nile Virus Assay.

    PubMed

    Burkhalter, Kristen L; Savage, Harry M

    2015-12-01

    We evaluated the utility of 2 types of commercially available antigens as positive controls in the Rapid Analyte Measurement Platform (RAMP®) West Nile virus (WNV) assay. Purified recombinant WNV envelope antigens and whole killed virus antigens produced positive RAMP results and either type would be useful as a positive control. Killed virus antigens provide operational and economic advantages and we recommend their use over purified recombinant antigens. We also offer practical applications for RAMP positive controls and recommendations for preparing them.

  1. Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier.

    PubMed

    Lazear, Helen M; Daniels, Brian P; Pinto, Amelia K; Huang, Albert C; Vick, Sarah C; Doyle, Sean E; Gale, Michael; Klein, Robyn S; Diamond, Michael S

    2015-04-22

    Although interferon-λ [also known as type III interferon or interleukin-28 (IL-28)/IL-29] restricts infection by several viruses, its inhibitory mechanism has remained uncertain. We used recombinant interferon-λ and mice lacking the interferon-λ receptor (IFNLR1) to evaluate the effect of interferon-λ on infection with West Nile virus, an encephalitic flavivirus. Cell culture studies in mouse keratinocytes and dendritic cells showed no direct antiviral effect of exogenous interferon-λ, even though expression of interferon-stimulated genes was induced. We observed no differences in West Nile virus burden between wild-type and Ifnlr1(-/-) mice in the draining lymph nodes, spleen, or blood. We detected increased West Nile virus infection in the brain and spinal cord of Ifnlr1(-/-) mice, yet this was not associated with a direct antiviral effect in mouse neurons. Instead, we observed an increase in blood-brain barrier permeability in Ifnlr1(-/-) mice. Treatment of mice with pegylated interferon-λ2 resulted in decreased blood-brain barrier permeability, reduced West Nile virus infection in the brain without affecting viremia, and improved survival against lethal virus challenge. An in vitro model of the blood-brain barrier showed that interferon-λ signaling in mouse brain microvascular endothelial cells increased transendothelial electrical resistance, decreased virus movement across the barrier, and modulated tight junction protein localization in a protein synthesis- and signal transducer and activator of transcription 1 (STAT1)-independent manner. Our data establish an indirect antiviral function of interferon-λ in which noncanonical signaling through IFNLR1 tightens the blood-brain barrier and restricts viral neuroinvasion and pathogenesis. Copyright © 2015, American Association for the Advancement of Science.

  2. West Nile Virus Encephalitis in a Barbary Macaque (Macaca sylvanus)

    PubMed Central

    Barker, Ian K.; Crawshaw, Graham J.; Bertelsen, Mads F.; Drebot, Michael A.; Andonova, Maya

    2004-01-01

    An aged Barbary ape (Macaca sylvanus) at the Toronto Zoo became infected with naturally acquired West Nile virus (WNV) encephalitis that caused neurologic signs, which, associated with other medical problems, led to euthanasia. The diagnosis was based on immunohistochemical assay of brain lesions, reverse transcriptase–polymerase chain reaction, and virus isolation. PMID:15200866

  3. Detection and sequencing of West Nile virus RNA from human urine and serum samples during the 2014 seasonal period.

    PubMed

    Nagy, Anna; Bán, Enikő; Nagy, Orsolya; Ferenczi, Emőke; Farkas, Ágnes; Bányai, Krisztián; Farkas, Szilvia; Takács, Mária

    2016-07-01

    West Nile virus, a widely distributed mosquito-borne flavivirus, is responsible for numerous animal and human infections in Europe, Africa and the Americas. In Hungary, the average number of human infections falls between 10 and 20 cases each year. The severity of clinically manifesting infections varies widely from the milder form of West Nile fever to West Nile neuroinvasive disease (WNND). In routine laboratory diagnosis of human West Nile virus infections, serological methods are mainly applied due to the limited duration of viremia. However, recent studies suggest that detection of West Nile virus RNA in urine samples may be useful as a molecular diagnostic test for these infections. The Hungarian National Reference Laboratory for Viral Zoonoses serologically confirmed eleven acute human infections during the 2014 seasonal period. In three patients with neurological symptoms, viral RNA was detected from both urine and serum specimens, albeit for a longer period and in higher copy numbers with urine. Phylogenetic analysis of the NS3 genomic region of three strains and the complete genome of one selected strain demonstrated that all three patients had lineage-2 West Nile virus infections. Our findings reaffirm the utility of viral RNA detection in urine as a molecular diagnostic procedure for diagnosis of West Nile virus infections.

  4. Use of an Internal Positive Control in a Multiplex Reverse Transcription-PCR To Detect West Nile Virus RNA in Mosquito Pools

    PubMed Central

    Eisler, Diane L.; McNabb, Alan; Jorgensen, Danielle R.; Isaac-Renton, Judith L.

    2004-01-01

    We report on the use of West Nile virus Armored RNA as an internal positive control (IPC) for the extraction and reverse transcription-PCR (RT-PCR) of RNA extracted from field-collected mosquitoes and on a multiplex real-time Taqman RT-PCR to simultaneously detect the 3′ noncoding region of West Nile virus and the West Nile virus NS5-2 region comprising the IPC. Mosquito pools from the province of British Columbia, Canada (n = 635), were tested in duplicate and found to be negative for West Nile virus and positive for the IPC. Known West Nile virus-positive supernatants from mosquito pools from the provinces of Alberta and Manitoba were tested in duplicate and found to be positive for both regions of the West Nile virus genome. The mean cycle threshold (Ct) value for the IPC in batch extraction controls ± 2 standard deviations was found to be 36.43 ± 1.78 cycles. IPCs of 98.4% (624) of West Nile virus-negative pools fell within this range, indicating the reproducibility of RNA extraction and RT-PCR for pools varying in mosquito genus and number. A comparison of mosquito pool genera revealed no significant genus effect on the Ct value of the IPC. The incorporation of West Nile virus Armored RNA as an IPC allows monitoring of RNA extraction and RT-PCR and detection of false-negative results due to failures in these processes or to PCR inhibition, respectively. PMID:14766868

  5. West Nile Virus in the United States — A Historical Perspective

    PubMed Central

    Roehrig, John T.

    2013-01-01

    Prior to 1999, West Nile virus (WNV) was a bit player in the screenplay of global vector-borne viral diseases. First discovered in the West Nile District of Uganda in 1937, this Culex sp.-transmitted virus was known for causing small human febrile outbreaks in Africa and the Middle East. Prior to 1995, the last major human WNV outbreak was in the 1950s in Israel. The epidemiology and ecology of WNV began to change in the mid-1990s when an epidemic of human encephalitis occurred in Romania. The introduction of WNV into Eastern Europe was readily explained by bird migration between Africa and Europe. The movement of WNV from Africa to Europe could not, however, predict its surprising jump across the Atlantic Ocean to New York City and the surrounding areas of the United States (U.S.). This movement of WNV from the Eastern to Western Hemisphere in 1999, and its subsequent dissemination throughout two continents in less than ten years is widely recognized as one of the most significant events in arbovirology during the last two centuries. This paper documents the early events of the introduction into and the spread of WNV in the Western Hemisphere. PMID:24335779

  6. Estimating West Nile virus transmission period in Pennsylvania using an optimized degree-day model.

    PubMed

    Chen, Shi; Blanford, Justine I; Fleischer, Shelby J; Hutchinson, Michael; Saunders, Michael C; Thomas, Matthew B

    2013-07-01

    Abstract We provide calibrated degree-day models to predict potential West Nile virus (WNV) transmission periods in Pennsylvania. We begin by following the standard approach of treating the degree-days necessary for the virus to complete the extrinsic incubation period (EIP), and mosquito longevity as constants. This approach failed to adequately explain virus transmission periods based on mosquito surveillance data from 4 locations (Harrisburg, Philadelphia, Pittsburgh, and Williamsport) in Pennsylvania from 2002 to 2008. Allowing the EIP and adult longevity to vary across time and space improved model fit substantially. The calibrated models increase the ability to successfully predict the WNV transmission period in Pennsylvania to 70-80% compared to less than 30% in the uncalibrated model. Model validation showed the optimized models to be robust in 3 of the locations, although still showing errors for Philadelphia. These models and methods could provide useful tools to predict WNV transmission period from surveillance datasets, assess potential WNV risk, and make informed mosquito surveillance strategies.

  7. West Nile virus among blood donors in the United States, 2003 and 2004.

    PubMed

    Stramer, Susan L; Fang, Chyang T; Foster, Gregory A; Wagner, Annette G; Brodsky, Jaye P; Dodd, Roger Y

    2005-08-04

    West Nile virus first appeared in the United States in 1999 and has since spread throughout the contiguous states, resulting in thousands of cases of disease. By 2002, it was clear that the virus could be transmitted by blood transfusion, and by the middle of 2003, essentially all blood donations were being tested for West Nile virus RNA with the use of investigational nucleic acid amplification tests; testing was performed on individual samples or on "minipools" of up to 16 donations. We analyzed data from the West Nile virus testing program of the American Red Cross for 2003 and 2004 to identify geographic and temporal trends. In areas with a high incidence of infection, individual donations were tested to increase the sensitivity of testing. Donors with reactive results participated in follow-up studies to confirm the original reactivity and to assess the natural history of infection. Routine testing in 2003 and 2004 identified 540 donations that were positive for West Nile virus RNA, of which 362 (67 percent) were IgM-antibody-negative and most likely infectious. Of the 540 positive donations, 148 (27 percent) were detectable only by testing of individual donations, but only 15 of the 148 (10 percent) were negative for IgM antibody. The overall frequencies of RNA-positive donations during the epidemic periods were 1.49 per 10,000 donations in 2003 and 0.44 per 10,000 in 2004. In 2004, 52 percent of the positive donations were from donors in four counties in southern California. Rapid implementation of a nucleic acid amplification test led to the prospective identification of 519 donors who were positive for West Nile virus RNA and the removal of more than 1000 potentially infectious related components from the blood supply of the Red Cross. No cases of transfusion-transmitted infection were confirmed among recipients of the tested blood. Copyright 2005 Massachusetts Medical Society.

  8. [Birds, mosquitoes and West Nile virus: little risk of West Nile fever in the Netherlands].

    PubMed

    Duijster, Janneke W; Stroo, C J Arjan; Braks, Marieta A H

    2016-01-01

    Due to increased incidence of West Nile fever (WNF) in Europe and the rapid spread of West Nile virus (WNV) in the US, it is commonly thought that it will only be a matter of time before WNV reaches the Netherlands. However, assessing whether WNV is really a threat to the Dutch population is challenging, due to the numerous factors affecting transmission of the virus. Some of these factors are known to limit the risk of WNF in the Netherlands. This risk is determined by the interaction between the pathogen (WNV), the vectors (Culex mosquitoes), the reservoirs (birds) and the exposure of humans to infected mosquitoes. In this paper, we discuss the factors influencing introduction, establishment and spread of WNV in the Netherlands. The probability that each of these three phases will occur in the Netherlands is currently relatively small, as is the risk of WNF infection in humans in the Netherlands.

  9. Globalization, land use and the invasion of West Nile virus

    PubMed Central

    Kilpatrick, A. Marm

    2012-01-01

    Many invasive species that have been spread through the globalization of trade and travel are infectious pathogens. A paradigmatic case is the introduction of West Nile virus (WNV) into North America in 1999. A decade of research on the ecology and evolution of WNV includes three findings that provide insight into the outcome of future viral introductions. First, WNV transmission in North America is highest in urbanized and agricultural habitats, in part because the hosts and vectors of WNV are abundant in human-modified areas. Second, after its introduction, the virus quickly adapted to infect local mosquito vectors more efficiently than the originally introduced strain. Third, highly focused feeding patterns of the mosquito vectors of WNV result in unexpected host species being important for transmission. These findings provide a framework for predicting and preventing the emergence of foreign vector-borne pathogens. PMID:22021850

  10. West Nile virus

    MedlinePlus

    ... of standing water, such as trash bins and plant saucers (mosquitos breed in stagnant water) Community spraying for mosquitoes may also reduce mosquito breeding. Alternative Names Encephalitis - West Nile; Meningitis - West Nile ...

  11. Introductions of West Nile Virus Strains to Mexico

    PubMed Central

    Deardorff, Eleanor; Estrada-Franco, José G.; Brault, Aaron C.; Navarro-Lopez, Roberto; Campomanes-Cortes, Arturo; Paz-Ramirez, Pedro; Solis-Hernandez, Mario; Ramey, Wanichaya N.; Davis, C. Todd; Beasley, David W.C.; Tesh, Robert B.; Barrett, Alan D.T.

    2006-01-01

    Complete genome sequencing of 22 West Nile virus isolates suggested 2 independent introductions into Mexico. A previously identified mouse-attenuated glycosylation variant was introduced into southern Mexico through the southeastern United States, while a common US genotype appears to have been introduced incrementally into northern Mexico through the southwestern United States. PMID:16494762

  12. Alexander the Great and West Nile Virus Encephalitis

    PubMed Central

    Marr, John S.

    2003-01-01

    Alexander the Great died in Babylon in 323 BC. His death at age 32 followed a 2-week febrile illness. Speculated causes of death have included poisoning, assassination, and a number of infectious diseases. One incident, mentioned by Plutarch but not considered by previous investigators, may shed light on the cause of Alexander’s death. The incident, which occurred as he entered Babylon, involved a flock of ravens exhibiting unusual behavior and subsequently dying at his feet. The inexplicable behavior of ravens is reminiscent of avian illness and death weeks before the first human cases of West Nile virus infection were identified in the United States. We posit that Alexander may have died of West Nile encephalitis. PMID:14725285

  13. Dynamics of West Nile virus evolution in mosquito vectors.

    PubMed

    Grubaugh, Nathan D; Ebel, Gregory D

    2016-12-01

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Chronic West Nile virus infection in kea (Nestor notabilis).

    PubMed

    Bakonyi, Tamás; Gajdon, Gyula K; Schwing, Raoul; Vogl, Wolfgang; Häbich, Annett-Carolin; Thaller, Denise; Weissenböck, Herbert; Rudolf, Ivo; Hubálek, Zdenek; Nowotny, Norbert

    2016-02-01

    Six kea (Nestor notabilis) in human care, naturally infected with West Nile virus (WNV) lineage 2 in Vienna, Austria, in 2008, developed mild to fatal neurological signs. WNV RNA persisted and the virus evolved in the birds' brains, as demonstrated by (phylo)genetic analyses of the complete viral genomes detected in kea euthanized between 2009 and 2014. WNV antibodies persisted in the birds, too. Chronic WNV infection in the brain might contribute to the circulation of the virus through oral transmission to predatory birds. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Vector-virus interactions and transmission dynamics of West Nile virus.

    PubMed

    Ciota, Alexander T; Kramer, Laura D

    2013-12-09

    West Nile virus (WNV; Flavivirus; Flaviviridae) is the cause of the most widespread arthropod-borne viral disease in the world and the largest outbreak of neuroinvasive disease ever observed. Mosquito-borne outbreaks are influenced by intrinsic (e.g., vector and viral genetics, vector and host competence, vector life-history traits) and extrinsic (e.g., temperature, rainfall, human land use) factors that affect virus activity and mosquito biology in complex ways. The concept of vectorial capacity integrates these factors to address interactions of the virus with the arthropod host, leading to a clearer understanding of their complex interrelationships, how they affect transmission of vector-borne disease, and how they impact human health. Vertebrate factors including host competence, population dynamics, and immune status also affect transmission dynamics. The complexity of these interactions are further exacerbated by the fact that not only can divergent hosts differentially alter the virus, but the virus also can affect both vertebrate and invertebrate hosts in ways that significantly alter patterns of virus transmission. This chapter concentrates on selected components of the virus-vector-vertebrate interrelationship, focusing specifically on how interactions between vector, virus, and environment shape the patterns and intensity of WNV transmission.

  16. Vector-Virus Interactions and Transmission Dynamics of West Nile Virus

    PubMed Central

    Ciota, Alexander T.; Kramer, Laura D.

    2013-01-01

    West Nile virus (WNV; Flavivirus; Flaviviridae) is the cause of the most widespread arthropod-borne viral disease in the world and the largest outbreak of neuroinvasive disease ever observed. Mosquito-borne outbreaks are influenced by intrinsic (e.g., vector and viral genetics, vector and host competence, vector life-history traits) and extrinsic (e.g., temperature, rainfall, human land use) factors that affect virus activity and mosquito biology in complex ways. The concept of vectorial capacity integrates these factors to address interactions of the virus with the arthropod host, leading to a clearer understanding of their complex interrelationships, how they affect transmission of vector-borne disease, and how they impact human health. Vertebrate factors including host competence, population dynamics, and immune status also affect transmission dynamics. The complexity of these interactions are further exacerbated by the fact that not only can divergent hosts differentially alter the virus, but the virus also can affect both vertebrate and invertebrate hosts in ways that significantly alter patterns of virus transmission. This chapter concentrates on selected components of the virus-vector-vertebrate interrelationship, focusing specifically on how interactions between vector, virus, and environment shape the patterns and intensity of WNV transmission. PMID:24351794

  17. West Nile virus in overwintering Culex mosquitoes, New York City, 2000.

    PubMed Central

    Nasci, R. S.; Savage, H. M.; White, D. J.; Miller, J. R.; Cropp, B. C.; Godsey, M. S.; Kerst, A. J.; Bennett, P.; Gottfried, K.; Lanciotti, R. S.

    2001-01-01

    After the 1999 West Nile (WN) encephalitis outbreak in New York, 2,300 overwintering adult mosquitoes were tested for WN virus by cell culture and reverse transcriptase-polymerase chain reaction. WN viral RNA and live virus were found in pools of Culex mosquitoes. Persistence in overwintering Cx. pipiens may be important in the maintenance of WN virus in the northeastern United States. PMID:11585542

  18. Corvidae feather pulp and West Nile virus detection

    USGS Publications Warehouse

    Docherty, D.E.; Romaine Long, R.; Griffin, Katie M.; Saito, E.K.

    2004-01-01

    We evaluated cloacal swab, vascular pulp of flight feather, and kidney and spleen pool samples from carcasses of members of the family Corvidae as sources of West Nile virus (WNV). The cloacal swab, kidney and spleen pool, and feather pulp were the source of WNV in 38%, 43%, and 77%, respectively, of the carcasses.

  19. Fatal West Nile virus infection in a white-tailed deer (Odocoileus virginianus).

    PubMed

    Miller, Debra L; Radi, Zaher A; Baldwin, Charles; Ingram, Dallas

    2005-01-01

    A 3-yr-old male white-tailed deer (Odocoileus virginianus) with a history of ataxia and tremors was submitted to the Tifton Veterinary Diagnostic and Investigational Laboratory (The University of Georgia, Tifton, Georgia, USA) for necropsy. Gross findings were unremarkable. Histologically, the brain had multifocal lymphoplasmacytic perivascular inflammation, scattered gliosis, and rare satellitosis. Mild hemorrhage and congestion in the retropharyngeal lymph nodes and mild lymphoid depletion in the tonsil were present. A reverse transcription-polymerase chain reaction test performed on brain yielded a positive result for West Nile virus. This represents the first report of fatal West Nile virus infection in a white-tailed deer.

  20. Antiviral Peptides Targeting the West Nile Virus Envelope Protein▿

    PubMed Central

    Bai, Fengwei; Town, Terrence; Pradhan, Deepti; Cox, Jonathan; Ashish; Ledizet, Michel; Anderson, John F.; Flavell, Richard A.; Krueger, Joanna K.; Koski, Raymond A.; Fikrig, Erol

    2007-01-01

    West Nile virus (WNV) can cause fatal murine and human encephalitis. The viral envelope protein interacts with host cells. A murine brain cDNA phage display library was therefore probed with WNV envelope protein, resulting in the identification of several adherent peptides. Of these, peptide 1 prevented WNV infection in vitro with a 50% inhibition concentration of 67 μM and also inhibited infection of a related flavivirus, dengue virus. Peptide 9, a derivative of peptide 1, was a particularly potent inhibitor of WNV in vitro, with a 50% inhibition concentration of 2.6 μM. Moreover, mice challenged with WNV that had been incubated with peptide 9 had reduced viremia and fatality compared with control animals. Peptide 9 penetrated the murine blood-brain barrier and was found in the brain parenchyma, implying that it may have antiviral activity in the central nervous system. These short peptides serve as the basis for developing new therapeutics for West Nile encephalitis and, potentially, other flaviviruses. PMID:17151121

  1. Drought and immunity determine the intensity of West Nile virus epidemics and climate change impacts

    DOE PAGES

    Paull, Sara H.; Horton, Daniel E.; Ashfaq, Moetasim; ...

    2017-02-08

    The effect of global climate change on infectious disease remains hotly debated because multiple extrinsic and intrinsic drivers interact to influence transmission dynamics in nonlinear ways. The dominant drivers of widespread pathogens, like West Nile virus, can be challenging to identify due to regional variability in vector and host ecology, with past studies producing disparate findings. Here, we used analyses at national and state scales to examine a suite of climatic and intrinsic drivers of continental-scale West Nile virus epidemics, including an empirically derived mechanistic relationship between temperature and transmission potential that accounts for spatial variability in vectors. We foundmore » that drought was the primary climatic driver of increased West Nile virus epidemics, rather than within-season or winter temperatures, or precipitation independently. Local-scale data from one region suggested drought increased epidemics via changes in mosquito infection prevalence rather than mosquito abundance. In addition, human acquired immunity following regional epidemics limited subsequent transmission in many states. We show that over the next 30 years, increased drought severity from climate change could triple West Nile virus cases, but only in regions with low human immunity. Lastly, these results illustrate how changes in drought severity can alter the transmission dynamics of vector-borne diseases.« less

  2. Drought and immunity determine the intensity of West Nile virus epidemics and climate change impacts

    PubMed Central

    Horton, Daniel E.; Ashfaq, Moetasim; Rastogi, Deeksha; Kramer, Laura D.; Diffenbaugh, Noah S.

    2017-01-01

    The effect of global climate change on infectious disease remains hotly debated because multiple extrinsic and intrinsic drivers interact to influence transmission dynamics in nonlinear ways. The dominant drivers of widespread pathogens, like West Nile virus, can be challenging to identify due to regional variability in vector and host ecology, with past studies producing disparate findings. Here, we used analyses at national and state scales to examine a suite of climatic and intrinsic drivers of continental-scale West Nile virus epidemics, including an empirically derived mechanistic relationship between temperature and transmission potential that accounts for spatial variability in vectors. We found that drought was the primary climatic driver of increased West Nile virus epidemics, rather than within-season or winter temperatures, or precipitation independently. Local-scale data from one region suggested drought increased epidemics via changes in mosquito infection prevalence rather than mosquito abundance. In addition, human acquired immunity following regional epidemics limited subsequent transmission in many states. We show that over the next 30 years, increased drought severity from climate change could triple West Nile virus cases, but only in regions with low human immunity. These results illustrate how changes in drought severity can alter the transmission dynamics of vector-borne diseases. PMID:28179512

  3. Drought and immunity determine the intensity of West Nile virus epidemics and climate change impacts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Paull, Sara H.; Horton, Daniel E.; Ashfaq, Moetasim

    The effect of global climate change on infectious disease remains hotly debated because multiple extrinsic and intrinsic drivers interact to influence transmission dynamics in nonlinear ways. The dominant drivers of widespread pathogens, like West Nile virus, can be challenging to identify due to regional variability in vector and host ecology, with past studies producing disparate findings. Here, we used analyses at national and state scales to examine a suite of climatic and intrinsic drivers of continental-scale West Nile virus epidemics, including an empirically derived mechanistic relationship between temperature and transmission potential that accounts for spatial variability in vectors. We foundmore » that drought was the primary climatic driver of increased West Nile virus epidemics, rather than within-season or winter temperatures, or precipitation independently. Local-scale data from one region suggested drought increased epidemics via changes in mosquito infection prevalence rather than mosquito abundance. In addition, human acquired immunity following regional epidemics limited subsequent transmission in many states. We show that over the next 30 years, increased drought severity from climate change could triple West Nile virus cases, but only in regions with low human immunity. Lastly, these results illustrate how changes in drought severity can alter the transmission dynamics of vector-borne diseases.« less

  4. Drought and immunity determine the intensity of West Nile virus epidemics and climate change impacts.

    PubMed

    Paull, Sara H; Horton, Daniel E; Ashfaq, Moetasim; Rastogi, Deeksha; Kramer, Laura D; Diffenbaugh, Noah S; Kilpatrick, A Marm

    2017-02-08

    The effect of global climate change on infectious disease remains hotly debated because multiple extrinsic and intrinsic drivers interact to influence transmission dynamics in nonlinear ways. The dominant drivers of widespread pathogens, like West Nile virus, can be challenging to identify due to regional variability in vector and host ecology, with past studies producing disparate findings. Here, we used analyses at national and state scales to examine a suite of climatic and intrinsic drivers of continental-scale West Nile virus epidemics, including an empirically derived mechanistic relationship between temperature and transmission potential that accounts for spatial variability in vectors. We found that drought was the primary climatic driver of increased West Nile virus epidemics, rather than within-season or winter temperatures, or precipitation independently. Local-scale data from one region suggested drought increased epidemics via changes in mosquito infection prevalence rather than mosquito abundance. In addition, human acquired immunity following regional epidemics limited subsequent transmission in many states. We show that over the next 30 years, increased drought severity from climate change could triple West Nile virus cases, but only in regions with low human immunity. These results illustrate how changes in drought severity can alter the transmission dynamics of vector-borne diseases. © 2017 The Author(s).

  5. Occurrence of West Nile virus antibodies in wild birds, horses, and humans in Poland.

    PubMed

    Niczyporuk, Jowita Samanta; Samorek-Salamonowicz, Elżbieta; Lecollinet, Sylvie; Pancewicz, Sławomir Andrzej; Kozdruń, Wojciech; Czekaj, Hanna

    2015-01-01

    Serum samples of 474 wild birds, 378 horses, and 42 humans with meningitis and lymphocytic meningitis were collected between 2010 and 2014 from different areas of Poland. West Nile virus (WNV) antibodies were detected using competition enzyme linked immunosorbent assays: ELISA-1 ID Screen West Nile Competition, IDvet, ELISA-2 ID Screen West Nile IgM Capture, and ELISA-3 Ingezim West Nile Compac. The antibodies were found in 63 (13.29%) out of 474 wild bird serum samples and in one (0.26%) out of 378 horse serum samples. Fourteen (33.33%) out of 42 sera from patients were positive against WNV antigen and one serum was doubtful. Positive samples obtained in birds were next retested with virus microneutralisation test to confirm positive results and cross-reactions with other antigens of the Japanese encephalitis complex. We suspect that positive serological results in humans, birds, and horses indicate that WNV can be somehow closely related with the ecosystem in Poland.

  6. Occurrence of West Nile Virus Antibodies in Wild Birds, Horses, and Humans in Poland

    PubMed Central

    Niczyporuk, Jowita Samanta; Samorek-Salamonowicz, Elżbieta; Lecollinet, Sylvie; Pancewicz, Sławomir Andrzej; Kozdruń, Wojciech; Czekaj, Hanna

    2015-01-01

    Serum samples of 474 wild birds, 378 horses, and 42 humans with meningitis and lymphocytic meningitis were collected between 2010 and 2014 from different areas of Poland. West Nile virus (WNV) antibodies were detected using competition enzyme linked immunosorbent assays: ELISA-1 ID Screen West Nile Competition, IDvet, ELISA-2 ID Screen West Nile IgM Capture, and ELISA-3 Ingezim West Nile Compac. The antibodies were found in 63 (13.29%) out of 474 wild bird serum samples and in one (0.26%) out of 378 horse serum samples. Fourteen (33.33%) out of 42 sera from patients were positive against WNV antigen and one serum was doubtful. Positive samples obtained in birds were next retested with virus microneutralisation test to confirm positive results and cross-reactions with other antigens of the Japanese encephalitis complex. We suspect that positive serological results in humans, birds, and horses indicate that WNV can be somehow closely related with the ecosystem in Poland. PMID:25866767

  7. West Nile Virus Isolation in Human and Mosquitoes, Mexico

    PubMed Central

    Elizondo-Quiroga, Darwin; Davis, C. Todd; Fernandez-Salas, Ildefonso; Escobar-Lopez, Roman; Olmos, Dolores Velasco; Gastalum, Lourdes Cecilia Soto; Acosta, Magaly Aviles; Elizondo-Quiroga, Armando; Gonzalez-Rojas, Jose I.; Cordero, Juan F. Contreras; Guzman, Hilda; Travassos da Rosa, Amelia; Blitvich, Bradley J.; Barrett, Alan D.T.; Beaty, Barry J.

    2005-01-01

    West Nile virus has been isolated for the first time in Mexico, from a sick person and from mosquitoes (Culex quinquefasciatus). Partial sequencing and analysis of the 2 isolates indicate that they are genetically similar to other recent isolates from northern Mexico and the western United States. PMID:16229779

  8. Vector competence of the stable fly (Diptera: Muscidae)for West Nile virus.

    USDA-ARS?s Scientific Manuscript database

    Stable flies, which are notorious pests of cattle and other livestock, were suspected of transmitting West Nile virus (WNV) among American white pelicans at the Medicine Lake Wildlife Refuge in northeastern Montana in 2006-2007. However the ability of stable flies to transmit the virus was unknown. ...

  9. Risk mapping of West Nile virus circulation in Spain, 2015.

    PubMed

    Sánchez-Gómez, Amaya; Amela, Carmen; Fernández-Carrión, Eduardo; Martínez-Avilés, Marta; Sánchez-Vizcaíno, José Manuel; Sierra-Moros, María José

    2017-05-01

    West Nile fever is an emergent disease in Europe. The objective of this study was to conduct a predictive risk mapping of West Nile Virus (WNV) circulation in Spain based on historical data of WNV circulation. Areas of Spain with evidence of WNV circulation were mapped based on data from notifications to the surveillance systems and a literature review. A logistic regression-based spatial model was used to assess the probability of WNV circulation. Data were analyzed at municipality level. Mean temperatures of the period from June to October, presence of wetlands and presence of Special Protection Areas for birds were considered as potential predictors. Two predictors of WNV circulation were identified: higher temperature [adjusted odds ratio (AOR) 2.07, 95% CI 1.82-2.35, p<0.01] and presence of wetlands (3.37, 95% CI 1.89-5.99, p<0.01). Model validations indicated good predictions: area under the ROC curve was 0.895 (95% CI 0.870-0.919) for internal validation and 0.895 (95% CI 0.840-0.951) for external validation. This model could support improvements of WNV risk- based surveillance in Spain. The importance of a comprehensive surveillance for WNF, including human, animal and potential vectors is highlighted, which could additionally result in model refinements. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Persistence of West Nile virus.

    PubMed

    Garcia, Melissa N; Hasbun, Rodrigo; Murray, Kristy O

    2015-02-01

    West Nile virus (WNV) is a widespread global pathogen that results in significant morbidity and mortality. Data from animal models provide evidence of persistent renal and neurological infection from WNV; however, the possibility of persistent infection in humans and long-term neurological and renal outcomes related to viral persistence remain largely unknown. In this paper, we provide a review of the literature related to persistent infection in parallel with the findings from cohorts of patients with a history of WNV infection. The next steps for enhancing our understanding of WNV as a persistent pathogen are discussed. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  11. West Nile virus infection and postoperative neurological symptoms: a case report and review of the literature.

    PubMed

    Moreland, Natalie C; Hemmer, Laura B; Koht, Antoun

    2014-08-01

    The incidence of West Nile virus, which may cause a range of clinical presentations including subclinical infections, mild febrile illness, meningitis, or encephalitis, has increased over recent years. Rare complications, including optic neuritis, also have been reported. A patient who presented with preoperative asymptomatic West Nile virus developed fever, altered mental status and temporary vision loss after elective multilevel spine fusion surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. West Nile Virus Infection in Commercial Waterfowl Operation, Wisconsin

    PubMed Central

    Kronenwetter-Koepel, Tamara A.; Vandermause, Mary F.; Reed, Kurt D.

    2006-01-01

    A West Nile virus (WNV) outbreak occurred at a commercial waterfowl operation in Wisconsin in 2005. Retrospective analysis of dead and live birds was conducted. WNV was detected by PCR in 84.1% of 88 dead birds; neutralizing antibodies were found in 14 of 30 randomly sampled asymptomatic or recovered birds. PMID:17073102

  13. Fusion loop peptide of the West Nile virus envelope protein is essential for pathogenesis and is recognized by a therapeutic cross-reactive human monoclonal antibody.

    PubMed

    Sultana, Hameeda; Foellmer, Harald G; Neelakanta, Girish; Oliphant, Theodore; Engle, Michael; Ledizet, Michel; Krishnan, Manoj N; Bonafé, Nathalie; Anthony, Karen G; Marasco, Wayne A; Kaplan, Paul; Montgomery, Ruth R; Diamond, Michael S; Koski, Raymond A; Fikrig, Erol

    2009-07-01

    West Nile virus is an emerging pathogen that can cause fatal neurological disease. A recombinant human mAb, mAb11, has been described as a candidate for the prevention and treatment of West Nile disease. Using a yeast surface display epitope mapping assay and neutralization escape mutant, we show that mAb11 recognizes the fusion loop, at the distal end of domain II of the West Nile virus envelope protein. Ab mAb11 cross-reacts with all four dengue viruses and provides protection against dengue (serotypes 2 and 4) viruses. In contrast to the parental West Nile virus, a neutralization escape variant failed to cause lethal encephalitis (at higher infectious doses) or induce the inflammatory responses associated with blood-brain barrier permeability in mice, suggesting an important role for the fusion loop in viral pathogenesis. Our data demonstrate that an intact West Nile virus fusion loop is critical for virulence, and that human mAb11 targeting this region is efficacious against West Nile virus infection. These experiments define the molecular determinant on the envelope protein recognized by mAb11 and demonstrate the importance of this region in causing West Nile encephalitis.

  14. Identification and biochemical characterization of small-molecule inhibitors of west nile virus serine protease by a high-throughput screen.

    PubMed

    Mueller, Niklaus H; Pattabiraman, Nagarajan; Ansarah-Sobrinho, Camilo; Viswanathan, Prasanth; Pierson, Theodore C; Padmanabhan, R

    2008-09-01

    West Nile virus and dengue virus are mosquito-borne flaviviruses that cause a large number of human infections each year. No vaccines or chemotherapeutics are currently available. These viruses encode a serine protease that is essential for polyprotein processing, a required step in the viral replication cycle. In this study, a high-throughput screening assay for the West Nile virus protease was employed to screen approximately 32,000 small-molecule compounds for identification of inhibitors. Lead inhibitor compounds with three distinct core chemical structures (1 to 3) were identified. In a secondary screening of selected compounds, two compounds, belonging to the 8-hydroxyquinoline family (compounds A and B) and containing core structure 1, were identified as potent inhibitors of the West Nile virus protease, with K(i) values of 3.2 +/- 0.3 microM and 3.4 +/- 0.6 microM, respectively. These compounds inhibited the dengue virus type 2 protease with K(i) values of 28.6 +/- 5.1 microM and 30.2 +/- 8.6 microM, respectively, showing some selectivity in the inhibition of these viral proteases. However, the compounds show no inhibition of cellular serine proteases, trypsin, or factor Xa. Kinetic analysis and molecular docking of compound B onto the known crystal structure of the West Nile virus protease indicate that the inhibitor binds in the substrate-binding cleft. Furthermore, compound B was capable of inhibiting West Nile virus RNA replication in cultured Vero cells (50% effective concentration, 1.4 +/- 0.4 microM; selectivity index, 100), presumably by inhibition of polyprotein processing.

  15. Clinical Manifestations and Outcomes of West Nile Virus Infection

    PubMed Central

    Sejvar, James J.

    2014-01-01

    Since the emergence of West Nile virus (WNV) in North America in 1999, understanding of the clinical features, spectrum of illness and eventual functional outcomes of human illness has increased tremendously. Most human infections with WNV remain clinically silent. Among those persons developing symptomatic illness, most develop a self-limited febrile illness. More severe illness with WNV (West Nile neuroinvasive disease, WNND) is manifested as meningitis, encephalitis or an acute anterior (polio) myelitis. These manifestations are generally more prevalent in older persons or those with immunosuppression. In the future, a more thorough understanding of the long-term physical, cognitive and functional outcomes of persons recovering from WNV illness will be important in understanding the overall illness burden. PMID:24509812

  16. Outbreak of West Nile virus infection in Greece, 2010.

    PubMed

    Danis, Kostas; Papa, Anna; Theocharopoulos, George; Dougas, Georgios; Athanasiou, Maria; Detsis, Marios; Baka, Agoritsa; Lytras, Theodoros; Mellou, Kassiani; Bonovas, Stefanos; Panagiotopoulos, Takis

    2011-10-01

    During 2010, an outbreak of West Nile virus infection occurred in Greece. A total of 197 patients with neuroinvasive disease were reported, of whom 33 (17%) died. Advanced age and a history of heart disease were independently associated with death, emphasizing the need for prevention of this infection in persons with these risk factors.

  17. West Nile Virus Encephalitis 16 Years Later.

    PubMed

    Kleinschmidt-DeMasters, Bette K; Beckham, J David

    2015-09-01

    Arboviruses (Arthropod-borne viruses) include several families of viruses (Flaviviridae, Togaviradae, Bunyaviradae, Reoviradae) that are spread by arthropod vectors, most commonly mosquitoes, ticks and sandflies. The RNA genome allows these viruses to rapidly adapt to ever-changing host and environmental conditions. Thus, these virus families are largely responsible for the recent expansion in geographic range of emerging viruses including West Nile virus (WNV), dengue virus and Chikungunya virus. This review will focus on WNV, especially as it has progressively spread westward in North America since its introduction in New York in 1999. By 2003, WNV infections in humans had reached almost all lower 48 contiguous United States (US) and since that time, fluctuations in outbreaks have occurred. Cases decreased between 2008 and 2011, followed by a dramatic flair in 2012, with the epicenter in the Dallas-Fort Worth region of Texas. The 2012 outbreak was associated with an increase in reported neuroinvasive cases. Neuroinvasive disease continues to be a problem particularly in the elderly and immunocompromised populations, although WNV infections also represented the second most frequent cause of pediatric encephalitis in these same years. Neuropathological features in cases from the 2012 epidemic highlight the extent of viral damage that can occur in the CNS. © 2015 International Society of Neuropathology.

  18. Reduced West Nile Virus Transmission Around Communal Roosts of Great-Tailed Grackle (Quiscalus mexicanus).

    PubMed

    Komar, Nicholas; Colborn, James M; Horiuchi, Kalanthe; Delorey, Mark; Biggerstaff, Brad; Damian, Dan; Smith, Kirk; Townsend, John

    2015-03-01

    West Nile virus has caused several outbreaks among humans in the Phoenix metropolitan area (Arizona, southwest USA) within the last decade. Recent ecologic studies have implicated Culex quinquefasciatus and Culex tarsalis as the mosquito vectors and identified three abundant passerine birds-great-tailed grackle (Quiscalus mexicanus), house sparrow (Passer domesticus), and house finch (Haemorhous mexicanus)-as key amplifiers among vertebrates. Nocturnal congregations of certain species have been suggested as critical for late summer West Nile virus amplification. We evaluated the hypothesis that house sparrow (P. domesticus) and/or great-tailed grackle (Q. mexicanus) communal roost sites (n = 22 and n = 5, respectively) in a primarily suburban environment were spatially associated with West Nile virus transmission indices during the 2010 outbreak of human neurological disease in metropolitan Phoenix. Spatial associations between human case residences and communal roosts were non-significant for house sparrows, and were negative for great-tailed grackle. Several theories that explain these observations are discussed, including the possibility that grackle communal roosts are protective.

  19. Reduced West Nile Virus Transmission Around Communal Roosts of Great-Tailed Grackle (Quiscalus mexicanus)

    PubMed Central

    Komar, Nicholas; Colborn, James M.; Horiuchi, Kalanthe; Delorey, Mark; Biggerstaff, Brad; Damian, Dan; Smith, Kirk; Townsend, John

    2016-01-01

    West Nile virus has caused several outbreaks among humans in the Phoenix metropolitan area (Arizona, southwest USA) within the last decade. Recent ecologic studies have implicated Culex quinquefasciatus and Culex tarsalis as the mosquito vectors and identified three abundant passerine birds—great-tailed grackle (Quiscalus mexicanus), house sparrow (Passer domesticus), and house finch (Haemorhous mexicanus)—as key amplifiers among vertebrates. Nocturnal congregations of certain species have been suggested as critical for late summer West Nile virus amplification. We evaluated the hypothesis that house sparrow (P. domesticus) and/or great-tailed grackle (Q. mexicanus) communal roost sites (n = 22 and n = 5, respectively) in a primarily suburban environment were spatially associated with West Nile virus transmission indices during the 2010 outbreak of human neurological disease in metropolitan Phoenix. Spatial associations between human case residences and communal roosts were non-significant for house sparrows, and were negative for great-tailed grackle. Several theories that explain these observations are discussed, including the possibility that grackle communal roosts are protective. PMID:25480320

  20. Detection Protocols for West Nile Virus in Mosquitoes, Birds, and Nonhuman Mammals.

    PubMed

    Kauffman, Elizabeth B; Franke, Mary A; Kramer, Laura D

    2016-01-01

    West Nile virus is the most widespread mosquito-borne virus in the world, and the most common cause of encephalitis in the USA. Surveillance for this medially important mosquito-borne pathogen is an important part of public health practice. Here we present protocols for testing environmental samples such as mosquitoes, nonvertebrate mammals, and birds for this virus, including RT-PCR, virus isolation in cell culture, and antigenic assays, as well as serologic assays for antibody detection.

  1. West Nile virus antibody prevalence in wild mammals, southern Wisconsin

    USGS Publications Warehouse

    Docherty, D.E.; Samuel, M.D.; Nolden, C.A.; Egstad, Kristina F.; Griffin, K.M.

    2006-01-01

    Twenty percent prevalence of West Nile virus antibody was found in free-ranging medium-sized Wisconsin mammals. No significant differences were noted in antibody prevalence with regard to sex, age, month of collection, or species. Our results suggest a similar route of infection in these mammals.

  2. West Nile Virus Fitness Costs in Different Mosquito Species.

    PubMed

    Coffey, Lark L; Reisen, William K

    2016-06-01

    West Nile virus (WNV) remains an important public health problem causing annual epidemics in the United States. Grubaugh et al. observed that WNV genetic divergence is dependent on the vector mosquito species. This suggests that specific WNV vector-bird species pairings may generate novel genotypes that could promote outbreaks. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Adult-onset opsoclonus-myoclonus syndrome due to West Nile Virus treated with intravenous immunoglobulin.

    PubMed

    Hébert, Julien; Armstrong, David; Daneman, Nick; Jain, Jennifer Deborah; Perry, James

    2017-02-01

    A 63-year-old female with no significant past medical history was presented with a 5-day history of progressive opsoclonus-myoclonus, headaches, and fevers. Her workup was significant only for positive West-Nile Virus serum serologies. She received a 2-day course of intravenous immunoglobulin (IvIG). At an 8-week follow up, she had a complete neurological remission. Adult-onset opsoclonus-myoclonus syndrome is a rare condition for which paraneoplastic and infectious causes have been attributed. To our knowledge, this is the first case reported of opsoclonus-myoclonus secondary to West-Nile Virus treated with intravenous immunoglobulin monotherapy.

  4. Domestic goose model for West Nile virus vaccine efficiency testing

    USDA-ARS?s Scientific Manuscript database

    West Nile virus (WNV) is an emergent pathogen in the Americas, first reported in New York during 1999, and has since spread across the United States (USA), Central and South America causing neurological disease in humans, horses and some bird species, including domestic geese. No WNV vaccines are li...

  5. West Nile Virus Antibody Prevalence in Wild Mammals, Southern Wisconsin

    PubMed Central

    Docherty, Douglas E.; Nolden, Cherrie A.; Egstad, Kristina F.; Griffin, Kathryn M.

    2006-01-01

    Twenty percent prevalence of West Nile virus antibody was found in free-ranging medium-sized Wisconsin mammals. No significant differences were noted in antibody prevalence with regard to sex, age, month of collection, or species. Our results suggest a similar route of infection in these mammals. PMID:17326959

  6. Wild Birds in Romania Are More Exposed to West Nile Virus Than to Newcastle Disease Virus.

    PubMed

    Paştiu, Anamaria Ioana; Pap, Péter László; Vágási, Csongor István; Niculae, Mihaela; Páll, Emőke; Domşa, Cristian; Brudaşcă, Florinel Ghe; Spînu, Marina

    2016-03-01

    The aim of this study was to evaluate the seroprevalence of West Nile virus (WNV) and Newcastle disease virus (NDV) in wild and domestic birds from Romania. During 2011-2014, 159 plasma samples from wild birds assigned to 11 orders, 27 families, and 61 species and from 21 domestic birds (Gallus gallus domesticus, Anas platyrhynchos domesticus) were collected. The sera were assayed by two commercial competitive enzyme-linked immunosorbent assay (cELISA) kits for antibodies against WNV and NDV. We found a high prevalence of WNV antibodies in both domestic (19.1%) and wild (32.1%) birds captured after the human epidemic in 2010. Moreover, the presence of anti-NDV antibodies among wild birds from Romania (5.4%) was confirmed serologically for the first time, as far as we are aware. Our findings provide evidence that wild birds, especially resident ones are involved in local West Nile and Newcastle disease enzootic and epizootic cycles. These may allow virus maintenance and spread and also enhance the chance of new outbreaks.

  7. West Nile Virus Drug Discovery

    PubMed Central

    Lim, Siew Pheng; Shi, Pei-Yong

    2013-01-01

    The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development. PMID:24300672

  8. West Nile virus drug discovery.

    PubMed

    Lim, Siew Pheng; Shi, Pei-Yong

    2013-12-03

    The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development.

  9. Evidence of West Nile virus infection in Nepal.

    PubMed

    Rutvisuttinunt, Wiriya; Chinnawirotpisan, Piyawan; Klungthong, Chonticha; Shrestha, Sanjaya Kumar; Thapa, Amod Bahadur; Pant, Arjun; Yingst, Samuel L; Yoon, In-Kyu; Fernandez, Stefan; Pavlin, Julie A

    2014-11-27

    Acute febrile illness is common among those seeking medical care and is frequently treated empirically with the underlying illness remaining undiagnosed in resource-poor countries. A febrile illness study was conducted 2009-2010 to identify known and unknown pathogens circulating in Nepal. Study methods included diagnostic testing and preliminary ELISA screening of acute and convalescent samples for diseases both known and unknown to be circulating in Nepal, including West Nile virus (WNV). The molecular assays including Polymerase Chain Reaction (PCR), Sanger sequencing and ultra deep sequencing on MiSeq Illumina Platform were conducted to further confirm the presence of WNV. The study enrolled 2,046 patients presenting undifferentiated febrile illness with unknown etiology. Sera from 14 out of 2,046 patients were tested positive for west nile virus (WNV) by nested Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Only two out of 14 cases were confirmed for the presence of WNV by sequencing and identified as WNV lineage 1 phylogentically. The two patients were adult males with fever and no neurological symptoms from Kathmandu and Bharatpur, Nepal. Two out of 2,046 serum samples contained fragments of WNV genome resembling WNV lineage 1, which is evidence of the continued spread of WNV which should be considered a possible illness cause in Nepal.

  10. West Nile virus in Europe: understanding the present to gauge the future.

    PubMed

    Reiter, P

    2010-03-11

    The appearance of West Nile virus in New York in 1999 and the unprecedented panzootic that followed, have stimulated a major research effort in the western hemisphere and a new interest in the presence of this virus in the Old World. This review considers current understanding of the natural history of this pathogen, with particular regard to transmission in Europe.

  11. Ensemble forecast of human West Nile virus cases and mosquito infection rates

    NASA Astrophysics Data System (ADS)

    Defelice, Nicholas B.; Little, Eliza; Campbell, Scott R.; Shaman, Jeffrey

    2017-02-01

    West Nile virus (WNV) is now endemic in the continental United States; however, our ability to predict spillover transmission risk and human WNV cases remains limited. Here we develop a model depicting WNV transmission dynamics, which we optimize using a data assimilation method and two observed data streams, mosquito infection rates and reported human WNV cases. The coupled model-inference framework is then used to generate retrospective ensemble forecasts of historical WNV outbreaks in Long Island, New York for 2001-2014. Accurate forecasts of mosquito infection rates are generated before peak infection, and >65% of forecasts accurately predict seasonal total human WNV cases up to 9 weeks before the past reported case. This work provides the foundation for implementation of a statistically rigorous system for real-time forecast of seasonal outbreaks of WNV.

  12. Ensemble forecast of human West Nile virus cases and mosquito infection rates.

    PubMed

    DeFelice, Nicholas B; Little, Eliza; Campbell, Scott R; Shaman, Jeffrey

    2017-02-24

    West Nile virus (WNV) is now endemic in the continental United States; however, our ability to predict spillover transmission risk and human WNV cases remains limited. Here we develop a model depicting WNV transmission dynamics, which we optimize using a data assimilation method and two observed data streams, mosquito infection rates and reported human WNV cases. The coupled model-inference framework is then used to generate retrospective ensemble forecasts of historical WNV outbreaks in Long Island, New York for 2001-2014. Accurate forecasts of mosquito infection rates are generated before peak infection, and >65% of forecasts accurately predict seasonal total human WNV cases up to 9 weeks before the past reported case. This work provides the foundation for implementation of a statistically rigorous system for real-time forecast of seasonal outbreaks of WNV.

  13. Opsoclonus myoclonus ataxia associated with West Nile virus infection: A dramatic presentation with benign prognosis?

    PubMed

    Zaltzman, Roy; Klein, Colin; Gordon, Carlos R

    2017-05-15

    Opsoclonus myoclonus and ataxia is a combination of severe neurological signs associated with several pathologic agents and conditions. Only few cases of opsoclonus have been related to West Nile virus infection. We report on a 61-year-old woman and on a 55-year-old man who had history of recent fever, who were hospitalized because of acute severe truncal ataxia, opsoclonus and tremor with minimal myoclonic jerks. A through work-up revealed the presence of both IgM and IgG antibodies against West Nile virus both in the serum and Cerebrospinal Fluid and excluded other causes known to be associated with this combination of neurological signs. The first case was treated with corticosteroids, followed by significant improvement, and the second recovered spontaneously. The acute combination of opsoclonus, severe truncal ataxia and tremor with a history of recent fever requires, during the relevant season and in the relevant geographic area, a search for a recent infection with West Nile virus. Though initially suffering from a devastating sickness, our patients eventually recovered. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Avian Hosts of West Nile Virus in Arizona

    PubMed Central

    Komar, Nicholas; Panella, Nicholas A.; Young, Ginger R.; Brault, Aaron C.; Levy, Craig E.

    2013-01-01

    West Nile virus (WNV) causes sporadic outbreaks of human encephalitis in Phoenix, Arizona. To identify amplifying hosts of WNV in the Phoenix area, we blood-sampled resident birds and measured antibody prevalence following an outbreak in the East Valley of metropolitan Phoenix during summer, 2010. House sparrow (Passer domesticus), house finch (Haemorhous mexicanus), great-tailed grackle (Quiscalus mexicanus), and mourning dove (Zenaida macroura) accounted for most WNV infections among locally resident birds. These species roost communally after early summer breeding. In September 2010, Culex vector-avian host contact was 3-fold greater at communal bird roosts compared with control sites, as determined by densities of resting mosquitoes with previous vertebrate contact (i.e., blood-engorged or gravid mosquitoes). Because of the low competence of mourning doves, these were considered weak amplifiers but potentially effective free-ranging sentinels. Highly competent sparrows, finches, and grackles were predicted to be key amplifying hosts for WNV in suburban Phoenix. PMID:23857022

  15. West Nile virus isolated from Virginia opossum ( Didelphis virginiana) in Northwest Missouri 2012

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bosco-Lauth, Angela; Harmon, Jessica; Lash, R. Ryan

    We describe the isolation of West Nile virus (WNV; Flaviviridae, flavivirus) from blood of a Virginia opossum ( Didelphis virginiana) collected in northwestern Missouri, USA in August 2012. Furthermore, sequencing determined that the virus was related to lineage 1a WNV02 strains. We discuss the role of wildlife in WNV disease epidemiology.

  16. West Nile virus isolated from Virginia opossum ( Didelphis virginiana) in Northwest Missouri 2012

    DOE PAGES

    Bosco-Lauth, Angela; Harmon, Jessica; Lash, R. Ryan; ...

    2014-12-01

    We describe the isolation of West Nile virus (WNV; Flaviviridae, flavivirus) from blood of a Virginia opossum ( Didelphis virginiana) collected in northwestern Missouri, USA in August 2012. Furthermore, sequencing determined that the virus was related to lineage 1a WNV02 strains. We discuss the role of wildlife in WNV disease epidemiology.

  17. West Nile virus and other arboviral diseases--United States, 2012.

    PubMed

    2013-06-28

    Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States. However, several other arboviruses also cause sporadic cases and seasonal outbreaks of neuroinvasive disease (e.g., meningitis, encephalitis, and acute flaccid paralysis). In 2012, CDC received reports of 5,780 nationally notifiable arboviral disease cases (excluding dengue). A large multistate outbreak of WNV disease accounted for 5,674 (98%) of reported cases, the highest number reported since 2003. Other reported etiologies included Eastern equine encephalitis virus (EEEV), Powassan virus (POWV), St. Louis encephalitis virus (SLEV), and California serogroup viruses such as La Crosse virus (LACV) and Jamestown Canyon virus (JCV). Arboviruses continue to cause serious illness in substantial numbers of persons in the United States. Maintaining surveillance remains important to identify outbreaks and guide prevention efforts.

  18. West Nile virus infection in killer whale, Texas, USA, 2007.

    PubMed

    St Leger, Judy; Wu, Guang; Anderson, Mark; Dalton, Les; Nilson, Erika; Wang, David

    2011-08-01

    In 2007, nonsuppurative encephalitis was identified in a killer whale at a Texas, USA, marine park. Panviral DNA microarray of brain tissue suggested West Nile virus (WNV); WNV was confirmed by reverse transcription PCR and sequencing. Immunohistochemistry demonstrated WNV antigen within neurons. WNV should be considered in cases of encephalitis in cetaceans.

  19. Detection of West Nile and Usutu Viruses in Italian Free Areas: Entomological Surveillance in Piemonte and Liguria Regions, 2014.

    PubMed

    Pautasso, Alessandra; Radaelli, Maria Cristina; Ballardini, Marco; Francese, Danila Raffaella; Verna, Federica; Modesto, Paola; Grattarola, Carla; Desiato, Rosanna; Bertolini, Silvia; Vitale, Nicoletta; Ferrari, Angelo; Rossini, Irene; Accorsi, Annalisa; Mosca, Andrea; Monaco, Federica; Savini, Giovanni; Prearo, Marino; Mignone, Walter; Chiavacci, Laura; Casalone, Cristina

    2016-04-01

    West Nile virus and Usutu virus have established in different parts of Italy over the past 10 years. Piemonte and Liguria Regions (Northwestern Italy) are known to be nonendemic areas, despite the presence of competent vectors and environmental conditions conducive to maintaining infection. This work evidences for the first time, through an entomological surveillance implemented on the basis of risk factor approach, the presence of West Nile and Usutu viruses in Piemonte and Liguria Regions (Northwestern Italy).

  20. Mosquito cell-derived West Nile virus replicon particles mimic arbovirus inoculum and have reduced spread in mice.

    PubMed

    Boylan, Brendan T; Moreira, Fernando R; Carlson, Tim W; Bernard, Kristen A

    2017-02-01

    Half of the human population is at risk of infection by an arthropod-borne virus. Many of these arboviruses, such as West Nile, dengue, and Zika viruses, infect humans by way of a bite from an infected mosquito. This infectious inoculum is insect cell-derived giving the virus particles distinct qualities not present in secondary infectious virus particles produced by infected vertebrate host cells. The insect cell-derived particles differ in the glycosylation of virus structural proteins and the lipid content of the envelope, as well as their induction of cytokines. Thus, in order to accurately mimic the inoculum delivered by arthropods, arboviruses should be derived from arthropod cells. Previous studies have packaged replicon genome in mammalian cells to produce replicon particles, which undergo only one round of infection, but no studies exist packaging replicon particles in mosquito cells. Here we optimized the packaging of West Nile virus replicon genome in mosquito cells and produced replicon particles at high concentration, allowing us to mimic mosquito cell-derived viral inoculum. These particles were mature with similar genome equivalents-to-infectious units as full-length West Nile virus. We then compared the mosquito cell-derived particles to mammalian cell-derived particles in mice. Both replicon particles infected skin at the inoculation site and the draining lymph node by 3 hours post-inoculation. The mammalian cell-derived replicon particles spread from the site of inoculation to the spleen and contralateral lymph nodes significantly more than the particles derived from mosquito cells. This in vivo difference in spread of West Nile replicons in the inoculum demonstrates the importance of using arthropod cell-derived particles to model early events in arboviral infection and highlights the value of these novel arthropod cell-derived replicon particles for studying the earliest virus-host interactions for arboviruses.

  1. Overview of West Nile Virus Transmission and Epidemiology.

    PubMed

    Troupin, Andrea; Colpitts, Tonya M

    2016-01-01

    West Nile virus (WNV) is a mosquito-borne flavivirus that can cause mild-to-severe disease in humans and horses. WNV was first documented in Uganda in 1937 and passed through the majority of Africa, West Asia, and Europe before arriving in the USA (with infections in New York City in 1999). After the spread of the virus on the US east coast, it traveled westward, northward, and southward through the USA and into Central and South America. WNV can cause fever, rashes, nausea, vomiting, and potentially neuroinvasive disease or death. The virus is sustained through a mosquito-bird-mosquito cycle and there are many species that are competent vectors. Unfortunately, there are no vaccines and the only treatment is supportive care. This chapter highlights the epidemiology and transmission of WNV and provides insight into some of the challenges of controlling WNV disease.

  2. West Nile virus outbreak among horses in New York State, 1999 and 2000.

    PubMed Central

    Trock, S. C.; Meade, B. J.; Glaser, A. L.; Ostlund, E. N.; Lanciotti, R. S.; Cropp, B. C.; Kulasekera, V.; Kramer, L. D.; Komar, N.

    2001-01-01

    West Nile (WN) virus was identified in the Western Hemisphere in 1999. Along with human encephalitis cases, 20 equine cases of WN virus were detected in 1999 and 23 equine cases in 2000 in New York. During both years, the equine cases occurred after human cases in New York had been identified. PMID:11585543

  3. West Nile Virus Infection in Killer Whale, Texas, USA, 2007

    PubMed Central

    Wu, Guang; Anderson, Mark; Dalton, Les; Nilson, Erika; Wang, David

    2011-01-01

    In 2007, nonsuppurative encephalitis was identified in a killer whale at a Texas, USA, marine park. Panviral DNA microarray of brain tissue suggested West Nile virus (WNV); WNV was confirmed by reverse transcription PCR and sequencing. Immunohistochemistry demonstrated WNV antigen within neurons. WNV should be considered in cases of encephalitis in cetaceans. PMID:21801643

  4. Pathogenicity of West Nile virus and response to vaccination in sandhill cranes (Grus canadensis) using a killed vaccine.

    PubMed

    Olsen, Glenn H; Miller, Kimberli J; Docherty, Douglas E; Bochsler, Valerie S; Sileo, Louis

    2009-06-01

    West Nile virus was introduced into the United States in the vicinity of New York, New York, USA in 1999. The virus has since killed large numbers of birds nationwide, especially, but not limited to, crows (Corvus brachyrhinchos). One sandhill crane (Grus canadensis) at the Bridgeport Zoo (Bridgeport, Connecticut, USA) reportedly died from West Nile virus, so sandhill cranes and endangered whooping cranes (Grus americana), both in the wild and in captive breeding colonies at United States Geological Service (USGS) Patuxent Wildlife Research Center (Laurel, Maryland, USA) were considered at risk. A killed vaccine in sandhill cranes was evaluated by vaccinating and then challenging these cranes with live West Nile virus. No sandhill cranes inoculated with the killed vaccine developed significant titers when compared with unvaccinated controls. No sandhill cranes inoculated with the vaccine and challenged with the virus died from West Nile virus infection. In addition, no unvaccinated challenged sandhill cranes died. However, 2 days postchallenge, vaccinated cranes had significantly less viremia (P < 0.05) than unvaccinated cranes. Seven days postchallenge vaccinated cranes had significantly less cloacal shedding of the virus (P < 0.05) than unvaccinated cranes and significantly less weight loss (P < 0.05) as compared with unvaccinated cranes. Vaccinated sandhill cranes developed significantly higher titers 14 days postchallenge and were viremic for shorter periods of time after challenge than unvaccinated individuals. Unvaccinated challenged cranes had glial cell aggregates in both the brain and brain stem areas, and this was not observed in vaccinated challenged cranes or in vaccinated unchallenged cranes.

  5. Pathogenicity of West Nile virus and response to vaccination in sandhill cranes (Grus canadensis) using a killed vaccine

    USGS Publications Warehouse

    Olsen, Glenn H.; Miller, Kimberli J.; Docherty, Douglas E.; Shearn-Bochsler, Valerie I.; Sileo, Louis

    2009-01-01

    West Nile virus was introduced into the United States in the vicinity of New York, New York, USA in 1999. The virus has since killed large numbers of birds nationwide, especially, but not limited to, crows (Corvus brachyrhinchos). One sandhill crane (Grus canadensis) at the Bridgeport Zoo (Bridgeport, Connecticut, USA) reportedly died from West Nile virus, so sandhill cranes and endangered whooping cranes (Grus americana), both in the wild and in captive breeding colonies at United States Geological Service (USGS) Patuxent Wildlife Research Center (Laurel, Maryland, USA) were considered at risk. A killed vaccine in sandhill cranes was evaluated by vaccinating and then challenging these cranes with live West Nile virus. No sandhill cranes inoculated with the killed vaccine developed significant titers when compared with unvaccinated controls. No sandhill cranes inoculated with the vaccine and challenged with the virus died from West Nile virus infection. In addition, no unvaccinated challenged sandhill cranes died. However, 2 days postchallenge, vaccinated cranes had significantly less viremia (P < 0.05) than unvaccinated cranes. Seven days postchallenge vaccinated cranes had significantly less cloacal shedding of the virus (P < 0.05) than unvaccinated cranes and significantly less weight loss (P < 0.05) as compared with unvaccinated cranes. Vaccinated sandhill cranes developed significantly higher titers 14 days postchallenge and were viremic for shorter periods of time after challenge than unvaccinated individuals. Unvaccinated challenged cranes had glial cell aggregates in both the brain and brain stem areas, and this was not observed in vaccinated challenged cranes or in vaccinated unchallenged cranes.

  6. Crystallization and preliminary X-ray diffraction analysis of West Nile virus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kaufmann, Barbel; Plevka, Pavel; Kuhn, Richard J.

    2010-05-25

    West Nile virus, a human pathogen, is closely related to other medically important flaviviruses of global impact such as dengue virus. The infectious virus was purified from cell culture using polyethylene glycol (PEG) precipitation and density-gradient centrifugation. Thin amorphously shaped crystals of the lipid-enveloped virus were grown in quartz capillaries equilibrated by vapor diffusion. Crystal diffraction extended at best to a resolution of about 25 {angstrom} using synchrotron radiation. A preliminary analysis of the diffraction images indicated that the crystals had unit-cell parameters a {approx_equal} b {approx_equal} 480 {angstrom}, {gamma} = 120{sup o}, suggesting a tight hexagonal packing of onemore » virus particle per unit cell.« less

  7. Climate change impacts on West Nile virus transmission in a global context

    PubMed Central

    Paz, Shlomit

    2015-01-01

    West Nile virus (WNV), the most widely distributed virus of the encephalitic flaviviruses, is a vector-borne pathogen of global importance. The transmission cycle exists in rural and urban areas where the virus infects birds, humans, horses and other mammals. Multiple factors impact the transmission and distribution of WNV, related to the dynamics and interactions between pathogen, vector, vertebrate hosts and environment. Hence, among other drivers, weather conditions have direct and indirect influences on vector competence (the ability to acquire, maintain and transmit the virus), on the vector population dynamic and on the virus replication rate within the mosquito, which are mostly weather dependent. The importance of climatic factors (temperature, precipitation, relative humidity and winds) as drivers in WNV epidemiology is increasing under conditions of climate change. Indeed, recent changes in climatic conditions, particularly increased ambient temperature and fluctuations in rainfall amounts, contributed to the maintenance (endemization process) of WNV in various locations in southern Europe, western Asia, the eastern Mediterranean, the Canadian Prairies, parts of the USA and Australia. As predictions show that the current trends are expected to continue, for better preparedness, any assessment of future transmission of WNV should take into consideration the impacts of climate change. PMID:25688020

  8. The outbreak of West Nile virus infection in the New York City area in 1999.

    PubMed

    Nash, D; Mostashari, F; Fine, A; Miller, J; O'Leary, D; Murray, K; Huang, A; Rosenberg, A; Greenberg, A; Sherman, M; Wong, S; Layton, M

    2001-06-14

    In late August 1999, an unusual cluster of cases of meningoencephalitis associated with muscle weakness was reported to the New York City Department of Health. The initial epidemiologic and environmental investigations suggested an arboviral cause. Active surveillance was implemented to identify patients hospitalized with viral encephalitis and meningitis. Cerebrospinal fluid, serum, and tissue specimens from patients with suspected cases underwent serologic and viral testing for evidence of arboviral infection. Outbreak surveillance identified 59 patients who were hospitalized with West Nile virus infection in the New York City area during August and September of 1999. The median age of these patients was 71 years (range, 5 to 95). The overall attack rate of clinical West Nile virus infection was at least 6.5 cases per million population, and it increased sharply with age. Most of the patients (63 percent) had clinical signs of encephalitis; seven patients died (12 percent). Muscle weakness was documented in 27 percent of the patients and flaccid paralysis in 10 percent; in all of the latter, nerve conduction studies indicated an axonal polyneuropathy in 14 percent. An age of 75 years or older was an independent risk factor for death (relative risk adjusted for the presence or absence of diabetes mellitus, 8.5; 95 percent confidence interval, 1.2 to 59.1), as was the presence of diabetes mellitus (age-adjusted relative risk, 5.1; 95 percent confidence interval, 1.5 to 17.3). This outbreak of West Nile meningoencephalitis in the New York City metropolitan area represents the first time this virus has been detected in the Western Hemisphere. Given the subsequent rapid spread of the virus, physicians along the eastern seaboard of the United States should consider West Nile virus infection in the differential diagnosis of encephalitis and viral meningitis during the summer months, especially in older patients and in those with muscle weakness.

  9. West Nile virus: immunity and pathogenesis.

    PubMed

    Lim, Stephanie M; Koraka, Penelope; Osterhaus, Albert D M E; Martina, Byron E E

    2011-06-01

    West Nile virus (WNV) is a neurotropic, arthropod-borne flavivirus that is maintained in an enzootic cycle between mosquitoes and birds, but can also infect and cause disease in horses and humans. WNV is endemic in parts of Africa, Europe, the Middle East, and Asia, and since 1999 has spread to North America, Mexico, South America, and the Caribbean. WNV infects the central nervous system (CNS) and can cause severe disease in a small minority of infected humans, mostly immunocompromised or the elderly. This review discusses some of the mechanisms by which the immune system can limit dissemination of WNV infection and elaborates on the mechanisms involved in pathogenesis. Reasons for susceptibility to WNV-associated neuroinvasive disease in less than 1% of cases remain unexplained, but one favored hypothesis is that the involvement of the CNS is associated with a weak immune response allowing robust WNV replication in the periphery and spread of the virus to the CNS.

  10. West Nile Virus Documented in Indonesia from Acute Febrile Illness Specimens

    PubMed Central

    Myint, Khin Saw Aye; Kosasih, Herman; Artika, I. Made; Perkasa, Aditya; Puspita, Mita; Ma'roef, Chairin Nisa; Antonjaya, Ungke; Ledermann, Jeremy P.; Powers, Ann M.; Alisjahbana, Bachti

    2014-01-01

    We report the presence of West Nile virus in a cryopreserved, dengue-negative serum specimen collected from an acute fever case on Java in 2004–2005. The strain belongs to genotype lineage 2, which has recently been implicated in human outbreaks in Europe. PMID:24420775

  11. [West Nile virus expanding in Europe].

    PubMed

    Reusken, Chantal B E M; van Maanen, C Kees; Martina, Byron E; Sonder, Gerard J B; van Gorp, Eric C M; Koopmans, Marion P G

    2011-01-01

    The areas of Europe in which West Nile virus (WNV)-transmission to humans is observed have expanded over the last few years, with endemic circulation amongst animals of southern Europe. This situation calls for heightened vigilance to the clinical presentation of WNV infection in humans. The average incubation period lasts 2-6 days. Of those infected, 20% will experience a mild, non-specific disease presentation such as high fever, headache, myalgia, possibly with rash and lymphadenopathy; <1% will develop severe neurological symptoms. Rare complications include: myelitis, optic neuritis, rhombencephalitis, polyradiculitis, myocarditis, pancreatitis and fulminant hepatitis. Clinicians should take WNV infection into consideration when making a differential diagnosis for such symptoms in patients who have returned from areas with potential virus circulation. Given the increase in the spread of WNV within Europe, this now holds true for continental travellers as well as those destined for the Americas, Africa and Asia. It is important to include the patient's travel history, clinical symptoms and any occurrences of vaccination against viruses causing Japanese encephalitis, tick-borne encephalitis and yellow fever into the diagnostic workup, as the antibodies against these diseases show cross-reactivity.

  12. Epidemiological and clinical aspects on West Nile virus, a globally emerging pathogen.

    PubMed

    David, Shoba; Abraham, Asha Mary

    2016-08-01

    Since the isolation of West Nile virus (WNV) in 1937, in Uganda, it has spread globally, causing significant morbidity and mortality. While birds serve as amplifier hosts, mosquitoes of the Culex genus function as vectors. Humans and horses are dead end hosts. The clinical manifestations of West Nile infection in humans range from asymptomatic illness to West Nile encephalitis. The laboratory offers an array of tests, the preferred method being detection of RNA and serum IgM for WNV, which, if detected, confirms the clinical diagnosis. Although no definitive antiviral therapy and vaccine are available for humans, many approaches are being studied. This article will review the current literature of the natural cycle, geographical distribution, virology, replication cycle, molecular epidemiology, pathogenesis, laboratory diagnosis, clinical manifestations, blood donor screening for WNV, treatment, prevention and vaccines.

  13. A recombinant influenza A virus expressing domain III of West Nile virus induces protective immune responses against influenza and West Nile virus.

    PubMed

    Martina, Byron E E; van den Doel, Petra; Koraka, Penelope; van Amerongen, Geert; Spohn, Gunther; Haagmans, Bart L; Provacia, Lisette B V; Osterhaus, Albert D M E; Rimmelzwaan, Guus F

    2011-04-26

    West Nile virus (WNV) continues to circulate in the USA and forms a threat to the rest of the Western hemisphere. Since methods for the treatment of WNV infections are not available, there is a need for the development of safe and effective vaccines. Here, we describe the construction of a recombinant influenza virus expressing domain III of the WNV glycoprotein E (Flu-NA-DIII) and its evaluation as a WNV vaccine candidate in a mouse model. FLU-NA-DIII-vaccinated mice were protected from severe body weight loss and mortality caused by WNV infection, whereas control mice succumbed to the infection. In addition, it was shown that one subcutaneous immunization with 10(5) TCID(50) Flu-NA-DIII provided 100% protection against challenge. Adoptive transfer experiments demonstrated that protection was mediated by antibodies and CD4+T cells. Furthermore, mice vaccinated with FLU-NA-DIII developed protective influenza virus-specific antibody titers. It was concluded that this vector system might be an attractive platform for the development of bivalent WNV-influenza vaccines.

  14. Surveillance for West Nile virus in clinic-admitted raptors, Colorado.

    PubMed

    Nemeth, Nicole; Kratz, Gail; Edwards, Eric; Scherpelz, Judy; Bowen, Richard; Komar, Nicholas

    2007-02-01

    In 2005, 13.5% of clinic-admitted raptors in northern Colorado tested positive for West Nile virus (WNV). Clinic-admitted-raptor surveillance detected WNV activity nearly 14 weeks earlier than other surveillance systems. WNV surveillance using live raptor admissions to rehabilitation clinics may offer a novel surveillance method and should be considered along with other techniques already in use.

  15. Fatal human eosinophilic meningo-encephalitis caused by CNS co-infection with Halicephalobus gingivalis and West Nile virus.

    PubMed

    Anwar, M A; Gokozan, H N; Ball, M K; Otero, J; McGwire, B S

    2015-10-01

    The saprophytic nematode Halicephalobus is a rare cause of fatal human meningo-encephalitis, and West Nile virus is neurotropic flavivirus implicated in a variety of clinical neurologic syndromes. Here we report a case of rapidly progressive CNS encephalopathy and death. Serologic, immuno-histochemical, histopathologic and nucleic acid studies demonstrate the presence of active Halicephalobus and West Nile virus in the CNS tissue. This is the first reported case of co-infection with these neurotropic pathogens. Copyright © 2015. Published by Elsevier Ireland Ltd.

  16. Domestic goose as a model for West Nile virus vaccine efficacy

    USDA-ARS?s Scientific Manuscript database

    West Nile virus (WNV) is an emergent pathogen in the Americas, first reported in New York during 1999, and has since spread across the United States (USA), Central and South America causing neurological disease in humans, horses and some bird species, including domestic geese. No WNV vaccines are li...

  17. Preclinical and clinical development of YFV 17D-based chimeric vaccines against dengue, West Nile and Japanese encephalitis viruses.

    PubMed

    Guy, Bruno; Guirakhoo, Farshad; Barban, Veronique; Higgs, Stephen; Monath, Thomas P; Lang, Jean

    2010-01-08

    Dengue viruses (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV) are major global health and growing medical problems. While a live-attenuated vaccine exists since decades against the prototype flavivirus, yellow fever virus (YFV), there is an urgent need for vaccines against dengue or West Nile diseases, and for improved vaccines against Japanese encephalitis. Live-attenuated chimeric viruses were constructed by replacing the genes coding for Premembrane (prM) and Envelope (E) proteins from YFV 17D vaccine strain with those of heterologous flaviviruses (ChimeriVax technology). This technology has been used to produce vaccine candidates for humans, for construction of a horse vaccine for West Nile fever, and as diagnostic reagents for dengue, Japanese encephalitis, West Nile and St. Louis encephalitis infections. This review focuses on human vaccines and their characterization from the early stages of research through to clinical development. Phenotypic and genetic properties and stability were examined, preclinical evaluation through in vitro or animal models, and clinical testing were carried out. Theoretical environmental concerns linked to the live and genetically modified nature of these vaccines have been carefully addressed. Results of the extensive characterizations are in accordance with the immunogenicity and excellent safety profile of the ChimeriVax-based vaccine candidates, and support their development towards large-scale efficacy trials and registration.

  18. Surveillance for West Nile Virus in Clinic-admitted Raptors, Colorado

    PubMed Central

    Kratz, Gail; Edwards, Eric; Scherpelz, Judy; Bowen, Richard; Komar, Nicholas

    2007-01-01

    In 2005, 13.5% of clinic-admitted raptors in northern Colorado tested positive for West Nile virus (WNV). Clinic-admitted–raptor surveillance detected WNV activity nearly 14 weeks earlier than other surveillance systems. WNV surveillance using live raptor admissions to rehabilitation clinics may offer a novel surveillance method and should be considered along with other techniques already in use. PMID:17479898

  19. West Nile virus population genetics and evolution

    PubMed Central

    Pesko, Kendra N.; Ebel, Gregory D.

    2015-01-01

    West Nile virus (WNV) (Flaviviridae: Flavivirus) is transmitted from mosquitoes to birds, but can cause fatal encephalitis in infected humans. Since its introduction into North America in New York in 1999, it has spread throughout the western hemisphere. Multiple outbreaks have also occurred in Europe over the last 20 years. This review highlights recent efforts to understand how host pressures impact viral population genetics, genotypic and phenotypic changes which have occurred in the WNV genome as it adapts to this novel environment, and molecular epidemiology of WNV worldwide. Future research directions are also discussed. PMID:22226703

  20. Neuroinvasive West Nile virus disease in Canada. The Saskatchewan experience.

    PubMed

    Téllez-Zenteno, José F; Hunter, Gary; Hernández-Ronquillo, Lizbeth; Haghir, Edrish

    2013-07-01

    West Nile virus (WNV) is a virus of the family Flaviviridae. The main route of human infection is through the bite of an infected mosquito. Approximately 90% of WNV infections in humans are asymptomatic, but neurologic manifestations can be severe. This study reviews the clinical profile of cases with neuroinvasive West Nile infection (NWNI) reported by the Surveillance program of the government of Saskatchewan in the Saskatoon Health Region (SHR). In 2007, 1456 cases of human West Nile cases were reported by the government of Saskatchewan in the whole province. One hundred and thirteen cases had severe symptoms of NWNI (8%), 1172 (80%) cases had mild symptoms of WNI and 171 (12%) had asymptomatic disease. Three hundred and fifty six cases were reported in the SHR, where 57 (16%) fulfilled criteria for NWNI. From the 57 cases, 39 (68%) were females. Nine (16%) patients had a history of recent camping, two (4%) reported outdoor sports and four (8%) reported outdoor activities not otherwise specified. Twenty five patients had headache (43.9%), 25 confusion (42.1%), 23 meningitis (40.4%), 17 encephalitis (29.8%), 14 encephalopathy (24.6%), 11 meningoencephalitis (19.3%), 10 tremor (17.5%), acute flaccid paralysis 10 (17.5%), myoclonus 1 (1.8%), nystagmus 2 (3.5%), diplopia 2 (3.5%), dizziness 2 (3.5%). Three patients died related with comorbidities during admission. During a year of high occurrence of WNI in Saskatchewan, 16% of cases developed NWNI. The recognition of neurological complications associated with WNI is important to improve their referral to tertiary centers.

  1. Early Warning System for West Nile Virus Risk Areas, California, USA

    PubMed Central

    Ahearn, Sean C.; McConchie, Alan; Glaser, Carol; Jean, Cynthia; Barker, Chris; Park, Bborie; Padgett, Kerry; Parker, Erin; Aquino, Ervic; Kramer, Vicki

    2011-01-01

    The Dynamic Continuous-Area Space-Time (DYCAST) system is a biologically based spatiotemporal model that uses public reports of dead birds to identify areas at high risk for West Nile virus (WNV) transmission to humans. In 2005, during a statewide epidemic of WNV (880 cases), the California Department of Public Health prospectively implemented DYCAST over 32,517 km2 in California. Daily risk maps were made available online and used by local agencies to target public education campaigns, surveillance, and mosquito control. DYCAST had 80.8% sensitivity and 90.6% specificity for predicting human cases, and κ analysis indicated moderate strength of chance-adjusted agreement for >4 weeks. High-risk grid cells (populations) were identified an average of 37.2 days before onset of human illness; relative risk for disease was >39× higher than for low-risk cells. Although prediction rates declined in subsequent years, results indicate DYCAST was a timely and effective early warning system during the severe 2005 epidemic. PMID:21801622

  2. Spatially explicit West Nile virus risk modeling in Santa Clara County, California

    USDA-ARS?s Scientific Manuscript database

    A previously created Geographic Information Systems model designed to identify regions of West Nile virus (WNV) transmission risk is tested and calibrated in Santa Clara County, California. American Crows that died from WNV infection in 2005 provide the spatial and temporal ground truth. Model param...

  3. Experimental susceptibility of wood ducks (Aix sponsa) for West Nile virus.

    PubMed

    Hofmeister, Erik; Porter, Robert E; Franson, J Christian

    2015-04-01

    Detection of West Nile virus (WNV) has been reported in a variety of wild ducks in the US, but little is known about the pathogenesis and outcome of exposure of the disease in these species. Previous experimental studies of WNV in ducks either have challenged a small number of ducks with WNV or have tested domesticated ducks. To determine susceptibility and immune response, we challenged 7-wk-old Wood Ducks (Aix sponsa) with a 1999 American Crow (Corvus brachyrhynchos) isolate of WNV. Wood Ducks were susceptible to infection with the virus, and, although clinical signs or mortality were not observed, microscopic lesions were noted, particularly in the heart and brain. West Nile virus viremia peaked on day 2 postinfection (pi) at 10(4.54) plaque-forming units (PFU) of virus/mL serum and WNV was shed orally (between 10(2) and 10(2.9) PFU per swab) and cloacally. Specific anti-WNV antibody response was rapid, with anti-WNV IgM detected on day 3 pi followed on day 5 pi by anti-WNV IgG. Neutralizing antibodies were detected by plaque-reduction neutralization assay in one duck on day 4 pi, and in all sampled ducks on day 5. These results indicate that Wood Ducks are susceptible to WNV, but it is unlikely that significant WNV mortality events occur in Wood Ducks or that they play a significant role in transmission. However, WNV viremia was sufficient, in theory, to infect mosquitoes, and oral and cloacal shedding of the virus may increase the risk of infection to other waterbirds.

  4. Experimental susceptibility of Wood Ducks (Aix sponsa) for West Nile virus

    USGS Publications Warehouse

    Hofmeister, Erik K.; Porter, Robert E.; Franson, J. Christian

    2015-01-01

    Detection of West Nile virus (WNV) has been reported in a variety of wild ducks in the US, but little is known about the pathogenesis and outcome of exposure of the disease in these species. Previous experimental studies of WNV in ducks either have challenged a small number of ducks with WNV or have tested domesticated ducks. To determine susceptibility and immune response, we challenged 7-wk-old Wood Ducks (Aix sponsa) with a 1999 American Crow (Corvus brachyrhynchos) isolate of WNV. Wood Ducks were susceptible to infection with the virus, and, although clinical signs or mortality were not observed, microscopic lesions were noted, particularly in the heart and brain. West Nile virus viremia peaked on day 2 postinfection (pi) at 104.54 plaque-forming units (PFU) of virus/mL serum and WNV was shed orally (between 102and 102.9 PFU per swab) and cloacally. Specific anti-WNV antibody response was rapid, with anti-WNV IgM detected on day 3 pi followed on day 5 pi by anti-WNV IgG. Neutralizing antibodies were detected by plaque-reduction neutralization assay in one duck on day 4 pi, and in all sampled ducks on day 5. These results indicate that Wood Ducks are susceptible to WNV, but it is unlikely that significant WNV mortality events occur in Wood Ducks or that ducks play a significant role in transmission. However, WNV viremia was sufficient, in theory, to infect mosquitoes, and oral and cloacal shedding of the virus may increase the risk of infection to other waterbirds.

  5. Does intra-individual neurocognitive variability relate to neuroinvasive disease and quality of life in West Nile Virus?

    PubMed

    Sheppard, David P; Woods, Steven Paul; Hasbun, Rodrigo; Salazar, Lucrecia; Nolan, Melissa S; Murray, Kristy O

    2018-04-25

    West Nile Virus (WNV) can be a neuroinvasive pathogen that may produce persistent mild-to-moderate neurocognitive impairments in some infected persons. Intra-individual variability (IIV) is an index of a person's performance across a neuropsychological test or battery, which is an indicator of neurocognitive control and integrity of prefrontal systems. The present study examined possible associations of IIV to neurological health and well-being in WNV infection. Participants included 84 adults with a range of clinical WNV disease (31 West Nile Encephalitis, 16 West Nile Meningitis, 37 West Nile Fever) who completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). IIV was operationalized as covariance of variation (CoV), or the intra-individual standard deviation across 5 age-adjusted RBANS standard scores divided by the mean of standard scores. Participants were assessed for health-related quality of life (QoL) using the RAND 36-item short form health survey (SF-36). Analyses revealed that the West Nile Encephalitis group had higher neurocognitive CoV compared to the West Nile Fever group, and this difference was associated with a medium effect size (Cohen's d = .52). Mixed linear models controlling for estimated IQ, activities of daily living, depression, neuroinvasive disease groups, and fatigue showed that higher RBANS CoV was associated with lower physical, but not mental health QoL. In persons with WNV infection, there is a modest association between elevations in IIV and encephalitis, and even subtle disruptions in neuropsychological functioning show relationships with important self-reported functioning as measured by physical health quality of life. Future studies should examine whether IIV predicts long-term health outcomes (e.g., mortality) in individuals infected with WNV.

  6. Spatially Explicit West Nile Virus Risk Modeling in Santa Clara County, CA

    USDA-ARS?s Scientific Manuscript database

    A geographic information systems model designed to identify regions of West Nile virus (WNV) transmission risk was tested and calibrated with data collected in Santa Clara County, California. American Crows that died from WNV infection in 2005, provided spatial and temporal ground truth. When the mo...

  7. Indigenous West Nile virus infections in horses in Albania.

    PubMed

    Berxholi, K; Ziegler, U; Rexhepi, A; Schmidt, K; Mertens, M; Korro, K; Cuko, A; Angenvoort, J; Groschup, M H

    2013-11-01

    Serum samples collected from 167 equines of 12 districts in Albania were tested for West Nile virus-specific antibodies by enzyme-linked immunosorbent assay and virus neutralization assay, using WNV lineage 1 and 2. In addition, 95 bird serum samples from Albania and 29 horse samples from Kosovo were tested in ELISA. An overall seroprevalence rate of 22% was found in horses from Albania, whereas no specific antibodies were found in the equine samples from Kosovo and the bird samples. This is the first report indicating WNV infections in animals in Albania, and the first reported seroprevalence study conducted for Kosovo. These results provide evidence for widespread infections of WNV in Albania. © 2013 Blackwell Verlag GmbH.

  8. Technologies for the development of West Nile virus vaccines.

    PubMed

    Ulbert, Sebastian; Magnusson, Sofia E

    2014-01-01

    West Nile virus (WNV), an emerging mosquito-borne and zoonotic flavivirus, continues to spread worldwide and represents a major problem for human and veterinary medicine. In recent years, severe outbreaks were observed in the USA and Europe with neighboring countries, and the virus is considered to be endemic in an increasing number of areas. Although most infections remain asymptomatic, WNV can cause severe, even fatal, neurological disease, which affects mostly the elderly and immunocompromised individuals. Several vaccines have been licensed in the veterinary sector, but no human vaccine is available today. This review summarizes recent strategies that are being followed to develop WNV vaccines with emphasis on technologies suitable for the use in humans.

  9. Ocular manifestations of emerging arboviruses: Dengue fever, Chikungunya, Zika virus, West Nile virus, and yellow fever.

    PubMed

    Merle, H; Donnio, A; Jean-Charles, A; Guyomarch, J; Hage, R; Najioullah, F; Césaire, R; Cabié, A

    2018-06-18

    Arboviruses are viral diseases transmitted by mosquitoes and tick bites. They are a major cause of morbidity and sometimes mortality. Their expansion is constant and due in part to climate change and globalization. Mostly found in tropical regions, arboviruses are sometimes the source of epidemics in Europe. Recently, the Chikungunya virus and the Zika virus were responsible for very large epidemics impacting populations that had never been in contact with those viruses. There are currently no effective antiviral treatments or vaccines. Ocular manifestations due to those infections are thus more frequent and increasingly better described. They are sometimes, as with Zika, complicated by a congenital ocular syndrome. The goal of this review is to describe the ophthalmological manifestations of Dengue fever, Chikungunya virus, Zika virus, West Nile virus, and yellow fever. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  10. Year-round West Nile virus activity, Gulf Coast region, Texas and Louisiana.

    PubMed

    Tesh, Robert B; Parsons, Ray; Siirin, Marina; Randle, Yvonne; Sargent, Chris; Guzman, Hilda; Wuithiranyagool, Taweesak; Higgs, Stephen; Vanlandingham, Dana L; Bala, Adil A; Haas, Keith; Zerinque, Brian

    2004-09-01

    West Nile virus (WNV) was detected in 11 dead birds and two mosquito pools collected in east Texas and southern Louisiana during surveillance studies in the winter of 2003 to 2004. These findings suggest that WNV is active throughout the year in this region of the United States.

  11. [West Nile virus. II. Immunopathophysiology in humans].

    PubMed

    Lanteri, Marion C; Diamond, Michael S; Norris, Philip J; Busch, Michael P

    2011-04-01

    Since its emergence in 1999 in America, West Nile virus (WNV) has become the leading cause of arboviral encephalitis in the United States. The infection is often asymptomatic but, when clinical manifestations occur, a broad range of symptoms is observed from flu-like symptoms to more serious neurological disorders that can sometimes lead to death. No treatment or vaccine is available for humans. Ongoing studies are trying to understand the host-virus dynamics that lead to the development of severe neurological symptoms in a minority of infected subjects. The amount of knowledge that was gained from parallel studies in animals and humans, comparing asymptomatic and symptomatic individuals, and using what was known of other Flaviviruses, will eventually translate to the development of potential therapeutic and prophylactic solutions. This review presents a synthesis of the most relevant findings concerning the immune response to WNV and its impact on disease outcome and gives an overview of the most promising therapeutic and prophylactic solutions.

  12. West nile virus disease and other arboviral diseases - United States, 2011.

    PubMed

    2012-07-13

    Arthropodborne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. Symptomatic infections most often manifest as a systemic febrile illness and, less commonly, as neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis). West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States. However, several other arboviruses also cause seasonal outbreaks and sporadic cases. In 2011, CDC received reports of 871 cases of nationally notifiable arboviral diseases (excluding dengue); etiological agents included WNV (712 cases), La Crosse virus (LACV) (130), Powassan virus (POWV) (16), St. Louis encephalitis virus (SLEV) (six), Eastern equine encephalitis virus (EEEV) (four), and Jamestown Canyon virus (JCV) (three). Of these, 624 (72%) were classified as neuroinvasive disease, for a national incidence of 0.20 per 100,000 population. WNV and other arboviruses continue to cause focal outbreaks and severe illness in substantial numbers of persons in the United States.

  13. Mosquitoes Transmit Unique West Nile Virus Populations during Each Feeding Episode.

    PubMed

    Grubaugh, Nathan D; Fauver, Joseph R; Rückert, Claudia; Weger-Lucarelli, James; Garcia-Luna, Selene; Murrieta, Reyes A; Gendernalik, Alex; Smith, Darci R; Brackney, Doug E; Ebel, Gregory D

    2017-04-25

    Arthropod-borne viruses (arboviruses), such as Zika virus, chikungunya virus, and West Nile virus (WNV), pose continuous threats to emerge and cause large epidemics. Often, these events are associated with novel virus variants optimized for local transmission that first arise as minorities within a host. Thus, the conditions that regulate the frequency of intrahost variants are important determinants of emergence. Here, we describe the dynamics of WNV genetic diversity during its transmission cycle. By temporally sampling saliva from individual mosquitoes, we demonstrate that virus populations expectorated by mosquitoes are highly diverse and unique to each feeding episode. After transmission to birds, however, most genetic diversity is removed by strong purifying selection. Further, transmission of potentially mosquito-adaptive WNV variants is strongly influenced by genetic drift in mosquitoes. These results highlight the complex evolutionary forces a novel virus variant must overcome to alter infection phenotypes at the population level. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Evaluating red-cockaded woodpeckers for exposure to West Nile Virus and blood parasites

    USGS Publications Warehouse

    Dusek, Robert J.; Richardson, D.; Egstad, Kristina F.; Heisey, Dennis M.

    2006-01-01

    A marked decline in the Picoides borealis (Red-cockaded Woodpecker [RCW]) population at Noxubee National Wildlife Refuge, MS, was observed in 2002. Demographic changes - including absence of hatch-year birds, decreases in size of known groups, and loss of known groups-were identified during annual fall surveys and are uncharacteristic of RCW populations. In 2003, a serosurvey of 28 adult RCWs was conducted to investigate the presence of West Nile virus (WNV) exposure in the population, possibly providing insight into whether WNV may have been responsible for this decline. Blood smears were also examined from these birds for blood parasites. We found no evidence of West Nile virus exposure or blood parasites in any of the RCWs sampled. Further monitoring of the RCW population and WNV activity in other species at Noxubee NWR is recommended to further evaluate the potential role of WNV and blood parasites in their decline.

  15. Lessons from the Murine Models of West Nile Virus Infection.

    PubMed

    McGruder, Brenna; Saxena, Vandana; Wang, Tian

    2016-01-01

    West Nile virus (WNV), a mosquito-borne, single positive-stranded RNA virus, has been the leading cause of arboviral encephalitis in the U.S. and other parts of the world over the past decade. Up to 50 % of WNV convalescent patients were reported to have long-term neurological sequelae or chronic kidney diseases. However, there are neither antiviral drugs nor vaccines available for humans. The underlying mechanism of the long-term sequelae is not clearly understood either. Animal models have been an effective tool to investigate viral pathogenesis and host immunity in humans. Here, we will review several commonly used murine models of WNV infection.

  16. A novel computer algorithm improves antibody epitope prediction using affinity-selected mimotopes: a case study using monoclonal antibodies against the West Nile virus E protein.

    PubMed

    Denisova, Galina F; Denisov, Dimitri A; Yeung, Jeffrey; Loeb, Mark B; Diamond, Michael S; Bramson, Jonathan L

    2008-11-01

    Understanding antibody function is often enhanced by knowledge of the specific binding epitope. Here, we describe a computer algorithm that permits epitope prediction based on a collection of random peptide epitopes (mimotopes) isolated by antibody affinity purification. We applied this methodology to the prediction of epitopes for five monoclonal antibodies against the West Nile virus (WNV) E protein, two of which exhibit therapeutic activity in vivo. This strategy was validated by comparison of our results with existing F(ab)-E protein crystal structures and mutational analysis by yeast surface display. We demonstrate that by combining the results of the mimotope method with our data from mutational analysis, epitopes could be predicted with greater certainty. The two methods displayed great complementarity as the mutational analysis facilitated epitope prediction when the results with the mimotope method were equivocal and the mimotope method revealed a broader number of residues within the epitope than the mutational analysis. Our results demonstrate that the combination of these two prediction strategies provides a robust platform for epitope characterization.

  17. Discovery of Nanomolar Dengue and West Nile Virus Protease Inhibitors Containing a 4-Benzyloxyphenylglycine Residue.

    PubMed

    Behnam, Mira A M; Graf, Dominik; Bartenschlager, Ralf; Zlotos, Darius P; Klein, Christian D

    2015-12-10

    The dengue virus (DENV) and West Nile Virus (WNV) NS2B-NS3 proteases are attractive targets for the development of dual-acting therapeutics against these arboviral pathogens. We present the synthesis and extensive biological evaluation of inhibitors that contain benzyl ethers of 4-hydroxyphenylglycine as non-natural peptidic building blocks synthesized via a copper-complex intermediate. A three-step optimization strategy, beginning with fragment growth of the C-terminal 4-hydroxyphenylglycine to the benzyloxy ether, followed by C- and N-terminal optimization, and finally fragment merging generated compounds with in vitro affinities in the low nanomolar range. The most promising derivative reached Ki values of 12 nM at the DENV-2 and 39 nM at the WNV proteases. Several of the newly discovered protease inhibitors yielded a significant reduction of dengue and West Nile virus titers in cell-based assays of virus replication, with an EC50 value of 3.4 μM at DENV-2 and 15.5 μM at WNV for the most active analogue.

  18. West Nile Virus and Usutu Virus Monitoring of Wild Birds in Germany.

    PubMed

    Michel, Friederike; Fischer, Dominik; Eiden, Martin; Fast, Christine; Reuschel, Maximilian; Müller, Kerstin; Rinder, Monika; Urbaniak, Sylvia; Brandes, Florian; Schwehn, Rebekka; Lühken, Renke; Groschup, Martin H; Ziegler, Ute

    2018-01-22

    By systematically setting up a unique nation-wide wild bird surveillance network, we monitored migratory and resident birds for zoonotic arthropod-borne virus infections, such as the flaviviruses West Nile virus (WNV) and Usutu virus (USUV). More than 1900 wild bird blood samples, from 20 orders and 136 different bird species, were collected between 2014 and 2016. Samples were investigated by WNV and USUV-specific real-time polymerase chain reactions as well as by differentiating virus neutralization tests. Dead bird surveillance data, obtained from organ investigations in 2016, were also included. WNV-specific RNA was not detected, whereas four wild bird blood samples tested positive for USUV-specific RNA. Additionally, 73 USUV-positive birds were detected in the 2016 dead bird surveillance. WNV neutralizing antibodies were predominantly found in long-distance, partial and short-distance migrants, while USUV neutralizing antibodies were mainly detected in resident wild bird species, preferentially with low seroprevalences. To date, WNV-specific RNA has neither been detected in wild birds, nor in mosquitoes, thus, we conclude that WNV is not yet present in Germany. Continued wild bird and mosquito monitoring studies are essential to detect the incursion of zoonotic viruses and to allow risk assessments for zoonotic pathogens.

  19. West Nile Virus and Usutu Virus Monitoring of Wild Birds in Germany

    PubMed Central

    Michel, Friederike; Fast, Christine; Reuschel, Maximilian; Müller, Kerstin; Urbaniak, Sylvia; Brandes, Florian; Schwehn, Rebekka; Groschup, Martin H.; Ziegler, Ute

    2018-01-01

    By systematically setting up a unique nation-wide wild bird surveillance network, we monitored migratory and resident birds for zoonotic arthropod-borne virus infections, such as the flaviviruses West Nile virus (WNV) and Usutu virus (USUV). More than 1900 wild bird blood samples, from 20 orders and 136 different bird species, were collected between 2014 and 2016. Samples were investigated by WNV and USUV-specific real-time polymerase chain reactions as well as by differentiating virus neutralization tests. Dead bird surveillance data, obtained from organ investigations in 2016, were also included. WNV-specific RNA was not detected, whereas four wild bird blood samples tested positive for USUV-specific RNA. Additionally, 73 USUV-positive birds were detected in the 2016 dead bird surveillance. WNV neutralizing antibodies were predominantly found in long-distance, partial and short-distance migrants, while USUV neutralizing antibodies were mainly detected in resident wild bird species, preferentially with low seroprevalences. To date, WNV-specific RNA has neither been detected in wild birds, nor in mosquitoes, thus, we conclude that WNV is not yet present in Germany. Continued wild bird and mosquito monitoring studies are essential to detect the incursion of zoonotic viruses and to allow risk assessments for zoonotic pathogens. PMID:29361762

  20. West nile virus and other arboviral diseases - United States, 2013.

    PubMed

    Lindsey, Nicole P; Lehman, Jennifer A; Staples, J Erin; Fischer, Marc

    2014-06-20

    Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States. However, several other arboviruses also cause sporadic cases and seasonal outbreaks of neuroinvasive disease (i.e., meningitis, encephalitis, and acute flaccid paralysis). This report summarizes surveillance data reported to CDC in 2013 for WNV and other nationally notifiable arboviruses, excluding dengue. Forty-seven states and the District of Columbia reported 2,469 cases of WNV disease. Of these, 1,267 (51%) were classified as WNV neuroinvasive disease, for a national incidence of 0.40 per 100,000 population. After WNV, the next most commonly reported cause of arboviral disease was La Crosse virus (LACV) (85 cases), followed by Jamestown Canyon virus (JCV), Powassan virus (POWV), and eastern equine encephalitis virus (EEEV) (eight). WNV and other arboviruses continue to cause serious illness in substantial numbers of persons annually. Maintaining surveillance remains important to help direct and promote prevention activities.

  1. Blood donor screening for West Nile virus (WNV) revealed acute Usutu virus (USUV) infection, Germany, September 2016.

    PubMed

    Cadar, Daniel; Maier, Philipp; Müller, Susanne; Kress, Julia; Chudy, Michael; Bialonski, Alexandra; Schlaphof, Alexander; Jansen, Stephanie; Jöst, Hanna; Tannich, Egbert; Runkel, Stefan; Hitzler, Walter E; Hutschenreuter, Gabriele; Wessiepe, Martina; Schmidt-Chanasit, Jonas

    2017-04-06

    Between 1 June and 31 December 2016, 13,023 blood donations from the University Hospital Aachen in Germany were routinely screened for West Nile virus (WNV) RNA using the cobas TaqScreen WNV Test. On 28 September 2016, one blood donor was tested positive. Subsequent analysis revealed an acute Usutu virus (USUV) infection. During the ongoing USUV epizootics in Germany, blood transfusion services, public health authorities and clinicians should be aware of increased human USUV infections. This article is copyright of The Authors, 2017.

  2. West Nile Virus Outbreak in Houston and Harris County, Texas, USA, 2014.

    PubMed

    Martinez, Diana; Murray, Kristy O; Reyna, Martin; Arafat, Raouf R; Gorena, Roberto; Shah, Umair A; Debboun, Mustapha

    2017-08-01

    Since 2002, West Nile virus (WNV) has been detected every year in Houston and the surrounding Harris County, Texas. In 2014, the largest WNV outbreak to date occurred, comprising 139 cases and causing 2 deaths. Additionally, 1,286 WNV-positive mosquito pools were confirmed, the most reported in a single mosquito season.

  3. A Brief Review of West Nile Virus Biology.

    PubMed

    Londono-Renteria, Berlin; Colpitts, Tonya M

    2016-01-01

    West Nile virus (WNV) is an arbovirus with increased global incidence in the last decade. It is also a major cause of human encephalitis in the USA. WNV is an arthropod-transmitted virus that mainly affects birds but humans become infected as incidental dead-end hosts which can cause outbreaks in naïve populations. The main vectors of WNV are mosquitoes of the genus Culex, which preferentially feed on birds. As in many other arboviruses, the characteristics that allow Flaviviruses like WNV to replicate and transmit to different hosts are encrypted in their genome, which also contains information for the production of structural and nonstructural proteins needed for host cell infection. WNV and other Flaviviruses have developed different strategies to establish infection, replication, and successful transmission. Most of these strategies include the diversion of the host's immune responses away from the virus. In this review, we describe the molecular structure and protein function of WNV with emphasis on protein involvement in the modulation of antiviral immune responses.

  4. Interventions against West Nile virus, Rift Valley fever virus, and Crimean-Congo hemorrhagic fever virus: where are we?

    PubMed

    Kortekaas, Jeroen; Ergönül, Onder; Moormann, Rob J M

    2010-10-01

    ARBO-ZOONET is an international network financed by the European Commission's seventh framework program. The major goal of this initiative is capacity building for the control of emerging viral vector-borne zoonotic diseases, with a clear focus on West Nile virus, Rift Valley fever virus, and Crimean-Congo hemorrhagic fever virus. To evaluate the status quo of control measures against these viruses, an ARBO-ZOONET meeting was held in Istanbul, Turkey, from 19 to 20 November 2009. The symposium consisted of three themes: (1) vaccines: new and existing ones; (2) antivirals: existing and new developments; and (3) antivector vaccines. In addition, a satellite workshop was held on epidemiology and diagnosis. The meeting brought together foremost international experts on the subjects from both within and without the ARBO-ZOONET consortium. This report highlights selected results from these presentations and major conclusions that emanated from the discussions held.

  5. West Nile Virus Encephalitis: The First Human Case Recorded in Brazil

    PubMed Central

    Vieira, Marcelo A. C. S.; Romano, Alessandro P. M.; Borba, Amaríles S.; Silva, Eliana V. P.; Chiang, Jannifer O.; Eulálio, Kelsen D.; Azevedo, Raimunda S. S.; Rodrigues, Sueli G.; Almeida-Neto, Walfrido S.; Vasconcelos, Pedro F. C.

    2015-01-01

    A Brazilian ranch worker with encephalitis and flaccid paralysis was evaluated in the regional Acute Encephalitis Syndromic Surveillance Program. This was the first Brazilian patient who met the Centers for Disease Control and Prevention (CDC) confirmation criteria for West Nile virus disease. Owing to the overlapping of neurological manifestations attributable to several viral infections of the central nervous system, this report exemplifies the importance of human acute encephalitis surveillance. The syndromic approach to human encephalitis cases may enable early detection of the introduction of unusual virus or endemic occurrence of potentially alarming diseases within a region. PMID:26055749

  6. Prognosis of West Nile virus associated acute flaccid paralysis: a case series.

    PubMed

    Johnstone, Jennie; Hanna, Steven E; Nicolle, Lindsay E; Drebot, Michael A; Neupane, Binod; Mahony, James B; Loeb, Mark B

    2011-08-19

    Little is known about the long-term health related quality of life outcomes in patients with West Nile virus associated acute flaccid paralysis. We describe the quality of life scores of seven patients with acute flaccid paralysis who presented to hospital between 2003 and 2006, and were followed for up to two years. Between 2003 and 2006, 157 symptomatic patients with West Nile virus were enrolled in a longitudinal cohort study of West Nile virus in Canada. Seven patients (4%) had acute flaccid paralysis. The first patient was a 55-year-old man who presented with left upper extremity weakness. The second patient was a 54-year-old man who presented with bilateral upper extremity weakness. The third patient was a 66-year-old woman who developed bilateral upper and lower extremity weakness. The fourth patient was a 67-year-old man who presented with right lower extremity weakness. The fifth patient was a 60-year-old woman who developed bilateral lower extremity weakness. The sixth patient was a 71-year-old man with a history of Parkinson's disease and acute onset bilateral lower extremity weakness. The seventh patient was a 52-year-old man who presented with right lower extremity weakness. All were Caucasian. Patients were followed for a mean of 1.1 years. At the end of follow-up the mean score on the Physical Component Summary of the Short-Form 36 scale had only slightly increased to 39. In contrast, mean score on the Mental Component Summary of the Short-Form 36 scale at the end of follow-up had normalized to 50. Despite the poor physical prognosis for patients with acute flaccid paralysis, the mental health outcomes are generally favorable.

  7. Mutation in West Nile Virus Structural Protein prM during Human Infection.

    PubMed

    Lustig, Yaniv; Lanciotti, Robert S; Hindiyeh, Musa; Keller, Nathan; Milo, Ron; Mayan, Shlomo; Mendelson, Ella

    2016-09-01

    A mutation leading to substitution of a key amino acid in the prM protein of West Nile virus (WNV) occurred during persistent infection of an immunocompetent patient. WNV RNA persisted in the patient's urine and serum in the presence of low-level neutralizing antibodies. This case demonstrates active replication of WNV during persistent infection.

  8. Prevalence of West Nile virus in migratory birds during spring and fall migration

    USGS Publications Warehouse

    Dusek, Robert J.; McLean, R.G.; Kramer, L.D.; Ubico, S.R.; Dupuis, A.P.; Ebel, G.D.; Guptill, S.C.

    2009-01-01

    To investigate the role of migratory birds in the dissemination of West Nile virus (WNV), we measured the prevalence of infectious WNV and specific WNV neutralizing antibodies in birds, principally Passeriformes, during spring and fall migrations in the Atlantic and Mississippi flyways from 2001-2003. Blood samples were obtained from 13,403 birds, representing 133 species. Specific WNV neutralizing antibody was detected in 254 resident and migratory birds, representing 39 species, and was most commonly detected in northern cardinals (Cardinalis cardinalis) (9.8%, N = 762) and gray catbirds (Dumetella carolinensis) (3.2%,N = 3188). West Nile virus viremias were detected in 19 birds, including 8 gray catbirds, and only during the fall migratory period. These results provide additional evidence that migratory birds may have been a principal agent for the spread of WNV in North America and provide data on the occurrence of WNV in a variety of bird species. Copyright ?? 2009 by The American Society of Tropical Medicine and Hygiene.

  9. Molecular Epidemiology and Evolution of West Nile Virus in North America

    PubMed Central

    Mann, Brian R.; McMullen, Allison R.; Swetnam, Daniele M.; Barrett, Alan D. T.

    2013-01-01

    West Nile virus (WNV) was introduced to New York in 1999 and rapidly spread throughout North America and into parts of Central and South America. Displacement of the original New York (NY99) genotype by the North America/West Nile 2002 (NA/WN02) genotype occurred in 2002 with subsequent identification of a novel genotype in 2003 in isolates collected from the southwestern Unites States region (SW/WN03 genotype). Both genotypes co-circulate to date. Subsequent WNV surveillance studies have confirmed additional genotypes in the United States that have become extinct due to lack of a selective advantage or stochastic effect; however, the dynamic emergence, displacement, and extinction of multiple WNV genotypes in the US from 1999–2012 indicates the continued evolution of WNV in North America. PMID:24135819

  10. Opsoclonus myoclonus syndrome: an unusual presentation for West Nile virus encephalitis

    PubMed Central

    Afzal, Aasim; Ashraf, Sahar

    2014-01-01

    A record number of West Nile virus (WNV) cases and fatalities seen in 2012 have brought to light the numerous manifestations of neuroinvasive disease. We report a case of opsoclonus myoclonus syndrome attributed to WNV and its clinical course after treatment with a combination of steroids and intravenous immunoglobulin. Our objective is to highlight opsoclonus myoclonus syndrome as a potential manifestation of WNV encephalitis. PMID:24688189

  11. Early-season avian deaths from West Nile virus as warnings of human infection

    USGS Publications Warehouse

    Guptill, S.C.; Julian, K.G.; Campbell, G.L.; Price, S.D.; Marfin, A.A.

    2003-01-01

    An analysis of 2001 and 2002 West Nile virus (WNV) surveillance data shows that counties that report WNV-infected dead birds early in the transmission season are more likely to report subsequent WNV disease cases in humans than are counties that do not report early WNV-infected dead birds.

  12. West Nile Virus workshop: scientific considerations for tissue donors.

    PubMed

    Brubaker, Scott A; Robert Rigney, P

    2012-08-01

    This report contains selected excerpts, presented as a summary, from a public workshop sponsored by the American Association of Tissue Banks (AATB) held to discuss West Nile Virus (WNV) and scientific considerations for tissue donors. The daylong workshop was held 9 July 2010 at the Ritz-Carlton Hotel at Tyson's Corner in McLean, Virginia, United States (U.S.). The workshop was designed to determine and discuss scientific information that is known, and what is not known, regarding WNV infection and transmission. The goal is to determine how to fill gaps in knowledge of WNV and tissue donation and transplantation by pursuing relevant scientific studies. This information should ultimately support decisions leading to appropriate tissue donor screening and testing considerations. Discussion topics were related to identifying these gaps and determining possible solutions. Workshop participants included subject-matter experts from the U.S. Food and Drug Administration, the Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Health Canada, the Public Health Agency of Canada, AATB-accredited tissue banks including reproductive tissue banks, accredited eye banks of the Eye Bank Association of America, testing laboratories, and infectious disease and organ transplantation professionals. After all presentations concluded, a panel addressed this question: "What are the scientific considerations for tissue donors and what research could be performed to address those considerations?" The slide presentations from the workshop are available at: http://www.aatb.org/2010-West-Nile-Virus-Workshop-Presentations.

  13. West Nile virus and North America: an unfolding story.

    PubMed

    Glaser, A

    2004-08-01

    Before the introduction of the West Nile virus (WNV) into the United States of America (USA) in 1999, conditions in North America were ideal for an arboviral epidemic. Such factors as the large, susceptible and non-immune animal and human populations, the presence of competent vectors, increasing international travel and commerce, existing methods for rapid dissemination and an ill-prepared animal and public health infrastructure all combined to create the essential elements for a severe animal and public health crisis--the 'perfect microbial storm'. The introduction of WNV into New York City was the final factor, serving as the catalyst to initiate one of the most significant epidemics in the USA. The spread of WNV across the country resulted in very large populations of wildlife, equines and people being exposed and infected. The epidemic is still not fully understood and its character continues to change and adapt. The recent recognition of a number of non-vector modes of transmission has revealed the disease as a greater threat and more difficult to control than first thought. West Nile virus gives every indication that it will become a permanent part of the 'medical landscape' of the USA, continuing to threaten wildlife, domestic animals and humans as a now endemic disease. This paper discusses the features of this extraordinary epidemic, and emphasises the need for an integrated surveillance system, greater diagnostic capacity and improved control strategies.

  14. Immune responses to West Nile virus infection in the central nervous system.

    PubMed

    Cho, Hyelim; Diamond, Michael S

    2012-12-17

    West Nile virus (WNV) continues to cause outbreaks of severe neuroinvasive disease in humans and other vertebrate animals in the United States, Europe, and other regions of the world. This review discusses our understanding of the interactions between virus and host that occur in the central nervous system (CNS), the outcome of which can be protection, viral pathogenesis, or immunopathogenesis. We will focus on defining the current state of knowledge of WNV entry, tropism, and host immune response in the CNS, all of which affect the balance between injury and successful clearance.

  15. Innate immune escape by Dengue and West Nile viruses.

    PubMed

    Gack, Michaela U; Diamond, Michael S

    2016-10-01

    Dengue (DENV) and West Nile (WNV) viruses are mosquito-transmitted flaviviruses that cause significant morbidity and mortality worldwide. Disease severity and pathogenesis of DENV and WNV infections in humans depend on many factors, including pre-existing immunity, strain virulence, host genetics and virus-host interactions. Among the flavivirus-host interactions, viral evasion of type I interferon (IFN)-mediated innate immunity has a critical role in modulating pathogenesis. DENV and WNV have evolved effective strategies to evade immune surveillance pathways that lead to IFN induction and to block signaling downstream of the IFN-α/β receptor. Here, we discuss recent advances in our understanding of the molecular mechanisms by which DENV and WNV antagonize the type I IFN response in human cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. The Global Ecology and Epidemiology of West Nile Virus

    PubMed Central

    Rios, Maria

    2015-01-01

    Since its initial isolation in Uganda in 1937 through the present, West Nile virus (WNV) has become an important cause of human and animal disease worldwide. WNV, an enveloped virus of the genus Flavivirus, is naturally maintained in an enzootic cycle between birds and mosquitoes, with occasional epizootic spillover causing disease in humans and horses. The mosquito vectors for WNV are widely distributed worldwide, and the known geographic range of WNV transmission and disease has continued to increase over the past 77 years. While most human infections with WNV are asymptomatic, severe neurological disease may develop resulting in long-term sequelae or death. Surveillance and preventive measures are an ongoing need to reduce the public health impact of WNV in areas with the potential for transmission. PMID:25866777

  17. Long-term neurological outcomes in West Nile virus-infected patients: an observational study.

    PubMed

    Weatherhead, Jill E; Miller, Vicki E; Garcia, Melissa N; Hasbun, Rodrigo; Salazar, Lucrecia; Dimachkie, Mazen M; Murray, Kristy O

    2015-05-01

    The Houston West Nile Cohort (HWNC) was founded in 2002 when West Nile virus (WNV) reached Houston, TX. The long-term outcomes following WNV infection are still mostly unknown, though neurological abnormalities up to 1 year postinfection have been documented. We report an observational study of neurological abnormalities at 1-3 and 8-11 years following WNV infection in the HWNC. We conducted standard neurological examinations at two separate time points to assess changes in neurological status over time. The majority of patients (86%, 30/35) with encephalitis had abnormal neurological exam findings at the time of the first assessment compared with uncomplicated fever (27%, 3/11) and meningitis (36%, 5/14) cases. At the time of the second assessment, 57% (4/7) of West Nile fever (WNF), 33% (2/6) of West Nile meningitis (WNM), and 36% (5/14) of West Nile encephalitis (WNE) had developed new neurological complications. The most common abnormalities noted were tandem gait, hearing loss, abnormal reflexes, and muscle weakness. Long-term neurological abnormalities were most commonly found in patients who experienced primary WNV encephalitis. New abnormalities may develop over time regardless of initial clinical infection. Future studies should aim to differentiate neurological consequences due to WNV neuroinvasive infection versus neurological decline related to comorbid conditions. © The American Society of Tropical Medicine and Hygiene.

  18. Dead Crow Reports and Location of Human West Nile Virus Cases, Chicago, 2002

    PubMed Central

    Jones, Roderick C.; Gibbs, Kevin; Paul, William

    2004-01-01

    During the summer and fall of 2002, an epidemic (223 cases) and epizootic of West Nile virus infections occurred in Chicago. Retrospective spatial analysis demonstrated that age-adjusted human case rates were three times higher inside geographic areas with high early-season crow deaths than outside these areas. PMID:15200837

  19. Epidemiological history and phylogeography of West Nile virus lineage 2.

    PubMed

    Ciccozzi, Massimo; Peletto, Simone; Cella, Eleonora; Giovanetti, Marta; Lai, Alessia; Gabanelli, Elena; Acutis, Pier Luigi; Modesto, Paola; Rezza, Giovanni; Platonov, Alexander E; Lo Presti, Alessandra; Zehender, Gianguglielmo

    2013-07-01

    West Nile virus (WNV) was first isolated in Uganda. In Europe WNV was sporadically detected until 1996, since then the virus has been regularly isolated from birds and mosquitoes and caused several outbreaks in horses and humans. Phylogenetic analysis showed two main different WNV lineages. The lineage 1 is widespread and segregates into different subclades (1a-c). WNV-1a includes numerous strains from Africa, America, and Eurasia. The spatio-temporal history of WNV-1a in Europe was recently described, identifying two main routes of dispersion, one in Eastern and the second in Western Europe. The West Nile lineage 2 (WNV-2) is mainly present in sub-Saharan Africa but has been recently emerged in Eastern and Western European countries. In this study we reconstruct the phylogeny of WNV-2 on a spatio-temporal scale in order to estimate the time of origin and patterns of geographical dispersal of the different isolates, particularly in Europe. Phylogeography findings obtained from E and NS5 gene analyses suggest that there were at least two separate introductions of WNV-2 from the African continent dated back approximately to the year 1999 (Central Europe) and 2000 (Russia), respectively. The epidemiological implications and clinical consequences of lineage 1 and 2 cocirculation deserve further investigations. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. West nile virus: characteristics of an african virus adapting to the third millennium world.

    PubMed

    Monini, Marina; Falcone, Emiliana; Busani, Luca; Romi, Roberto; Ruggeri, Franco Maria

    2010-04-22

    The emergence and spread of West Nile Virus (WNV) from North through South America during the last decade, and the recent outbreaks of disease in both humans and horses in Europe suggest that the epidemiology of this infection is evolving. WNV is now considered among the emerging threats for both human and veterinary public health in areas like Europe where it was previously regarded to as an exotic agent. Further knowledge has built up from studies investigating the characteristics of the virus and its genome evolution capacity, the adaptation to new avian host species, the changes in vector competence and biology, and the host-pathogen interactions, including the immune response. Also, the new needs for preparedness to future major outbursts of disease have stimulated research on virus detection and characterization, filling the gaps in both specialized diagnostic technology and the need for field rapid assays. This review will present an overview of WNV virology, remarking the impact of virus diversity and evolution on theoretical and practical aspects involved in both risk definition, detection and control of infection.

  1. Archival Isolates Confirm a Single Topotype of West Nile Virus in Australia

    PubMed Central

    Huang, Bixing; Prow, Natalie A; van den Hurk, Andrew F.; Allcock, Richard J. N.; Moore, Peter R.; Doggett, Stephen L.; Warrilow, David

    2016-01-01

    West Nile virus is globally wide-spread and causes significant disease in humans and animals. The evolution of West Nile virus Kunjin subtype in Australia (WNVKUN) was investigated using archival samples collected over a period of 50 years. Based on the pattern of fixed amino acid substitutions and time-stamped molecular clock analyses, a single long-term lineage (or topotype) was inferred. This implies that a bottleneck exists such that regional strains eventually die out and are replaced with strains from a single source. This was consistent with current hypotheses regarding the distribution of WNVKUN, whereby the virus is enzootic in northern Australia and is disseminated to southern states by water-birds or mosquitoes after flooding associated with above average rainfall. In addition, two previous amino acid changes associated with pathogenicity, an N-Y-S glycosylation motif in the envelope protein and a phenylalanine at amino acid 653 in the RNA polymerase, were both detected in all isolates collected since the 1980s. Changes primarily occurred due to stochastic drift. One fixed substitution each in NS3 and NS5, subtly changed the chemical environment of important functional groups, and may be involved in fine-tuning RNA synthesis. Understanding these evolutionary changes will help us to better understand events such as the emergence of the virulent strain in 2011. PMID:27906966

  2. West Nile virus 'circulation' in Vojvodina, Serbia: Mosquito, bird, horse and human surveillance.

    PubMed

    Petrić, Dušan; Petrović, Tamaš; Hrnjaković Cvjetković, Ivana; Zgomba, Marija; Milošević, Vesna; Lazić, Gospava; Ignjatović Ćupina, Aleksandra; Lupulović, Diana; Lazić, Sava; Dondur, Dragan; Vaselek, Slavica; Živulj, Aleksandar; Kisin, Bratislav; Molnar, Tibor; Janku, Djordje; Pudar, Dubravka; Radovanov, Jelena; Kavran, Mihaela; Kovačević, Gordana; Plavšić, Budimir; Jovanović Galović, Aleksandra; Vidić, Milan; Ilić, Svetlana; Petrić, Mina

    2017-02-01

    Efforts to detect West Nile virus (WNV) in the Vojvodina province, northern Serbia, commenced with human and mosquito surveillance in 2005, followed by horse (2009) and wild bird (2012) surveillance. The knowledge obtained regarding WNV circulation, combined with the need for timely detection of virus activity and risk assessment resulted in the implementation of a national surveillance programme integrating mosquito, horse and bird surveillance in 2014. From 2013, the system showed highly satisfactory results in terms of area specificity (the capacity to indicate the spatial distribution of the risk for human cases of West Nile neuroinvasive disease - WNND) and sensitivity to detect virus circulation even at the enzootic level. A small number (n = 50) of Culex pipiens (pipiens and molestus biotypes, and their hybrids) females analysed per trap/night, combined with a high number of specimens in the sample, provided variable results in the early detection capacity at different administrative levels (NUTS2 versus NUTS3). The clustering of infected mosquitoes, horses, birds and human cases of WNND in 2014-2015 was highly significant, following the south-west to north-east direction in Vojvodina (NUTS2 administrative level). Human WNND cases grouped closest with infected mosquitoes in 2014, and with wild birds/mosquitoes in 2015. In 2014, sentinel horses showed better spatial correspondence with human WNND cases than sentinel chickens. Strong correlations were observed between the vector index values and the incidence of human WNND cases recorded at the NUTS2 and NUTS3 levels. From 2010, West Nile virus was detected in mosquitoes sampled at 43 different trap stations across Vojvodina. At 14 stations (32.56%), WNV was detected in two different (consecutive or alternate) years, at 2 stations in 3 different years, and in 1 station during 5 different years. Based on these results, integrated surveillance will be progressively improved to allow evidence-based adoption of

  3. Community diversity of mosquitoes and their microbes across different habitats endemic for West Nile Virus and other arthropod-borne diseases

    NASA Astrophysics Data System (ADS)

    Liu, R.; Bennett, S. N.; Thongsripong, P.; Chandler, J. S.

    2013-12-01

    Mosquitoes have long been vectors for disease, and humans, birds, and other vertebrates have served their role as hosts in the transmission cycle of arthropod-borne viruses. In California, there are several mosquito species that act as vectors, transmitting such disease agents as Western equine and St. Louis encephalitis viruses, filarial nematodes, Plasmodium (which causes malaria), and West Nile virus (WNV). Last year (2012-2013), California had over 450 reported cases of West Nile Virus in humans (http://westnile.ca.gov/). To begin to understand mosquitoes and their role in the bay area as vectors of diseases, including West Nile Virus, we trapped mosquitoes from various sites and examined their microbiomes, including bacteria, fungi, viruses, and eukaryotes. Study sites were in Marin, San Mateo, and San Francisco counties, in areas that represented, respectively, rural, suburban, and urban habitats. The mosquitoes were identified through morphological characteristics, and verified molecularly by sequencing of the cytochrome oxidase I (COI) gene extracted from a leg. Most mosquitoes were collected from San Mateo and Mill Valley and were identified as Culiseta incidens. Data from traditional culture-based and next-generation 454 sequencing methods applied to mosquito whole bodies, representing their microbiomes, will be discussed, to determine how mosquito and microbial diversity varies across sites sampled in the San Francisco Bay area.

  4. West Nile Virus Range Expansion into British Columbia

    PubMed Central

    Henry, Bonnie; Mak, Sunny; Fraser, Mieke; Taylor, Marsha; Li, Min; Cooper, Ken; Furnell, Allen; Wong, Quantine; Morshed, Muhammad

    2010-01-01

    In 2009, an expansion of West Nile virus (WNV) into the Canadian province of British Columbia was detected. Two locally acquired cases of infection in humans and 3 cases of infection in horses were detected by ELISA and plaque-reduction neutralization tests. Ten positive mosquito pools were detected by reverse transcription PCR. Most WNV activity in British Columbia in 2009 occurred in the hot and dry southern Okanagan Valley. Virus establishment and amplification in this region was likely facilitated by above average nightly temperatures and a rapid accumulation of degree-days in late summer. Estimated exposure dates for humans and initial detection of WNV-positive mosquitoes occurred concurrently with a late summer increase in Culex tarsalis mosquitoes (which spread western equine encephalitis) in the southern Okanagan Valley. The conditions present during this range expansion suggest that temperature and Cx. tarsalis mosquito abundance may be limiting factors for WNV transmission in this portion of the Pacific Northwest. PMID:20678319

  5. Molecular evolution of lineage 2 West Nile virus.

    PubMed

    McMullen, Allison R; Albayrak, Harun; May, Fiona J; Davis, C Todd; Beasley, David W C; Barrett, Alan D T

    2013-02-01

    Since the 1990s West Nile virus (WNV) has become an increasingly important public health problem and the cause of outbreaks of neurological disease. Genetic analyses have identified multiple lineages with many studies focusing on lineage 1 due to its emergence in New York in 1999 and its neuroinvasive phenotype. Until recently, viruses in lineage 2 were not thought to be of public health importance due to few outbreaks of disease being associated with viruses in this lineage. However, recent epidemics of lineage 2 in Europe (Greece and Italy) and Russia have shown the increasing importance of this lineage. There are very few genetic studies examining isolates belonging to lineage 2. We have sequenced the full-length genomes of four older lineage 2 WNV isolates, compared them to 12 previously published genomic sequences and examined the evolution of this lineage. Our studies show that this lineage has evolved over the past 300-400 years and appears to correlate with a change from mouse attenuated to virulent phenotype based on previous studies by our group. This evolution mirrors that which is seen in lineage 1 isolates, which have also evolved to a virulent phenotype over the same period of time.

  6. West Nile virus in Tunisia, 2014: First isolation from mosquitoes.

    PubMed

    Wasfi, F; Dachraoui, K; Cherni, S; Bosworth, A; Barhoumi, W; Dowall, S; Chelbi, I; Derbali, M; Zoghlami, Z; Beier, J C; Zhioua, E

    2016-07-01

    Several outbreaks of human West Nile virus (WNV) infections were reported in Tunisia during the last two decades. Serological studies on humans as well as on equine showed intensive circulation of WNV in Tunisia. However, no virus screening of mosquitoes for WNV has been performed in Tunisia. In the present study, we collected mosquito samples from Central Tunisia to be examined for the presence of flaviviruses. A total of 102 Culex pipiens mosquitoes were collected in September 2014 from Central Tunisia. Mosquitoes were pooled according to the collection site, date and sex with a maximum of 5 specimens per pool and tested for the presence of flaviviruses by conventional reverse transcription heminested PCR and by a specific West Nile virus real time reverse transcription PCR. Of a total of 21 pools tested, 7 were positive for WNV and no other flavivirus could be evidenced in mosquito pools. In addition, WNV was isolated on Vero cells. Phylogenetic analysis showed that recent Tunisian WNV strains belong to lineage 1 WNV and are closely related to the Tunisian strain 1997 (PAH 001). This is the first detection and isolation of WNV from mosquitoes in Tunisia. Some areas of Tunisia are at high risk for human WNV infections. WNV is likely to cause future sporadic and foreseeable outbreaks. Therefore, it is of major epidemiological importance to set up an entomological surveillance as an early alert system. Timely detection of WNV should prompt vector control to prevent future outbreaks. In addition, education of people to protect themselves from mosquito bites is of major epidemiological importance as preventive measure against WNV infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Atypical presentation of West Nile virus in a newly diagnosed human immunodeficiency virus patient in New York City.

    PubMed

    Josekutty, Joby; Yeh, Richard; Mathew, Sheena; Ene, Ada; Ramessar, Nina; Trinidad, Jennilee

    2013-04-01

    Central nervous system manifestations of West Nile virus (WNV) infection include meningitis, encephalitis, and poliomyelitis-like syndrome. We describe a 44-year-old man with no past medical history who presented with a meningoencephalitic syndrome and spastic paralysis bilaterally in the upper and lower extremities, hyperreflexia, and myoclonus and was ultimately diagnosed as being infected with HIV and WNV.

  8. Mosquito and West Nile virus surveillance in northeast Montana, U.S.A., 2005-2006

    USDA-ARS?s Scientific Manuscript database

    Mosquito and West Nile virus surveillance was conducted on a National Wildlife Refuge in northeast Montana, 2005-2006, during which outbreaks of WNV in a colony of American white pelicans (Pelecanus erythrorhynchos Gmelin) resulted in juvenile mortality rates of 30 and 31%. During both years, flood...

  9. Not the Usual Viral Suspects: Parvovirus B19, West Nile Virus, and Human T-Cell Lymphotrophic Virus Infections After Kidney Transplantation.

    PubMed

    Razonable, Raymund R

    2016-09-01

    Kidney transplant recipients are at increased risk of developing clinical disease due to uncommon opportunistic viral pathogens. Refractory anemia is classically associated with parvovirus B19 infection. West Nile virus has the propensity to cause fever and neurologic symptoms, while spastic paresis and lymphoma can be triggered by human T cell lymphotrophic virus. In this review article, the epidemiology, clinical manifestations, diagnosis and treatment of less common viruses are discussed in the setting of kidney transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Identifying environmental risk factors and mapping the risk of human West Nile virus in South Dakota.

    NASA Astrophysics Data System (ADS)

    Hess, A.; Davis, J. K.; Wimberly, M. C.

    2017-12-01

    Human West Nile virus (WNV) first arrived in the USA in 1999 and has since then spread across the country. Today, the highest incidence rates are found in the state of South Dakota. The disease occurrence depends on the complex interaction between the mosquito vector, the bird host and the dead-end human host. Understanding the spatial domain of this interaction and being able to identify disease transmission hotspots is crucial for effective disease prevention and mosquito control. In this study we use geospatial environmental information to understand what drives the spatial distribution of cases of human West Nile virus in South Dakota and to map relative infection risk across the state. To map the risk of human West Nile virus in South Dakota, we used geocoded human case data from the years 2004-2016. Satellite data from the Landsat ETM+ and MODIS for the years 2003 to 2016 were used to characterize environmental patterns. From these datasets we calculated indices, such as the normalized differenced vegetation index (NDVI) and the normalized differenced water index (NDWI). In addition, datasets such as the National Land Data Assimilation System (NLDAS), National Land Cover Dataset (NLCD), National Wetland inventory (NWI), National Elevation Dataset (NED) and Soil Survey Geographic Database (SSURGO) were utilized. Environmental variables were summarized for a buffer zone around the case and control points. We used a boosted regression tree model to identify the most important variables describing the risk of WNV infection. We generated a risk map by applying this model across the entire state. We found that the highest relative risk is present in the James River valley in northeastern South Dakota. Factors that were identified as influencing the transmission risk include inter-annual variability of vegetation cover, water availability and temperature. Land covers such as grasslands, low developed areas and wetlands were also found to be good predictors for human

  11. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus.

    PubMed

    Brass, Abraham L; Huang, I-Chueh; Benita, Yair; John, Sinu P; Krishnan, Manoj N; Feeley, Eric M; Ryan, Bethany J; Weyer, Jessica L; van der Weyden, Louise; Fikrig, Erol; Adams, David J; Xavier, Ramnik J; Farzan, Michael; Elledge, Stephen J

    2009-12-24

    Influenza viruses exploit host cell machinery to replicate, resulting in epidemics of respiratory illness. In turn, the host expresses antiviral restriction factors to defend against infection. To find host cell modifiers of influenza A H1N1 viral infection, we used a functional genomic screen and identified over 120 influenza A virus-dependency factors with roles in endosomal acidification, vesicular trafficking, mitochondrial metabolism, and RNA splicing. We discovered that the interferon-inducible transmembrane proteins IFITM1, 2, and 3 restrict an early step in influenza A viral replication. The IFITM proteins confer basal resistance to influenza A virus but are also inducible by interferons type I and II and are critical for interferon's virustatic actions. Further characterization revealed that the IFITM proteins inhibit the early replication of flaviviruses, including dengue virus and West Nile virus. Collectively this work identifies a family of antiviral restriction factors that mediate cellular innate immunity to at least three major human pathogens. Copyright 2009 Elsevier Inc. All rights reserved.

  12. Diagnostic aptitude of West Nile virus-like particles expressed in insect cells.

    PubMed

    Rebollo, Belén; Sarraseca, Javier; Rodríguez, Mª José; Sanz, Antonio; Jiménez-Clavero, Miguel Ángel; Venteo, Ángel

    2018-02-10

    West Nile virus is a globally spread zoonotic arbovirus. The laboratory diagnosis of WNV infection relies on virus identification by RT-PCR or on specific antibody detection by serological tests, such as ELISA or virus-neutralization. These methods usually require a preparation of the whole virus as antigen, entailing biosafety issues and therefore requiring BSL-3 facilities. For this reason, recombinant antigenic structures enabling effective antibody recognition comparable to that of the native virions, would be advantageous as diagnostic reagents. WNV virions are enveloped spherical particles made up of 3 structural proteins (C, capsid; M, membrane and E, envelope) enclosing the viral RNA. This study describes the co-expression of these 3 proteins yielding non-infectious virus-like particles (VLPs) and the results of the initial assessment of these VLPs, used instead of the whole virus, that were shown to perform correctly in two different ELISAs for WNV diagnosis. Copyright © 2018. Published by Elsevier Inc.

  13. West Nile Virus Retinopathy and Associations with Long Term Neurological and Neurocognitive Sequelae.

    PubMed

    Hasbun, Rodrigo; Garcia, Melissa N; Kellaway, Judianne; Baker, Laura; Salazar, Lucrecia; Woods, Steven Paul; Murray, Kristy O

    2016-01-01

    West Nile virus (WNV) has emerged as an important vector-borne pathogen in North America, with more than 3 million estimated to have been infected. Retinopathy from WNV infection has been previously reported in acute cases, though those prior reports did not evaluate the risk of retinopathy based on clinical severity of neurologic disease. The purpose of this cross-sectional study was to perform comprehensive ophthalmological and neurological examinations on 111 patients with a history of West Nile virus infection and describe the ocular manifestations. Out of 111 patients, 27 (24%) had evidence for West Nile virus associated retinopathy (WNVR); this observation was higher (49%) in those patients who initially presented with encephalitis. Individuals with WNVR had more frequent involvement of the macula and peripheral involvement compared to those patients without WNVR (p<0.05). WNVR was also associated with a greater likelihood of abnormal reflexes on neurological exam, poorer learning, greater dependence in activities of daily living, and lower quality of life (p<0.05). WNVR was seen more frequently in elderly patients (age > 60 years), and was associated with higher rates of diabetes mellitus and a history of encephalitis (p<0.05). A multivariable logistic regression revealed that only a history of encephalitis was independently associated with WNVR [Adjusted Odds Ratio = 4.9 (1.8-13.2); p = 0.001]. Our study found that WNVR occurs in one fourth of patients with a history of WNV infection and is more frequently observed in those with apparent severe neurological sequelae (e.g., encephalitis). The clinical relevance of WNVR was supported by its associations with dependence in activities of daily living and lower quality of life. This unique evaluation of WNV patients included fundoscopic examinations and their associations with neurologic impairment. Our findings can be used during ophthalmological consultation for the evaluation, treatment and rehabilitation

  14. West Nile virus transmission and ecology in birds

    USGS Publications Warehouse

    McLean, R.G.; Ubico, S.R.; Docherty, D.E.; Hansen, W.R.; Sileo, L.; Mcnamara, T.S.

    2001-01-01

    The ecology of the strain of West Nile virus (WNV) introduced into the United States in 1999 has similarities to the native flavivirus, St. Louis encephalitis (SLE) virus, but has unique features not observed with SLE virus or with WNV in the old world. The primary route of transmission for most of the arboviruses in North America is by mosquito, and infected native birds usually do not suffer morbidity or mortality. An exception to this pattern is eastern equine encephalitis virus, which has an alternate direct route of transmission among nonnative birds, and some mortality of native bird species occurs. The strain of WNV circulating in the northeastern United States is unique in that it causes significant mortality in exotic and native bird species, especially in the American crow (Corvus brachyrhynchos). Because of the lack of information on the susceptibility and pathogenesis of WNV for this species, experimental studies were conducted at the USGS National Wildlife Health Center. In two separate studies, crows were inoculated with a 1999 New York strain of WNV, and all experimentally infected crows died. In one of the studies, control crows in regular contact with experimentally inoculated crows in the same room but not inoculated with WNV succumbed to infection. The direct transmission between crows was most likely by the oral route. Inoculated crows were viremic before death, and high titers of virus were isolated from a variety of tissues. The significance of the experimental direct transmission among captive crows is unknown.

  15. Human West Nile virus infection in Bosnia and Herzegovina.

    PubMed

    Ahmetagić, Sead; Petković, Jovan; Hukić, Mirsada; Smriko-Nuhanović, Arnela; Piljić, Dilista

    2015-02-01

    To describe the first two cases of West Nile virus (WNV) neuroinvasive infections in Bosnia and Herzegovina. At the Clinic for Infectious Diseases of the University Clinical Centre Tuzla, Bosnia and Herzegovina (BiH), specific screening for WNV infection was performed on patients with neuroinvasive diseases from 1 August to 31 October 2013. Serum samples were tested for the presence of WNV IgM and IgG antibodies using enzyme-linked immunosorbent assay (ELISA); positive serum samples were further analyzed by detection of WNV nucleic acid of two distinct lineages (lineage 1 and lineage 2) in sera by RT-PCR. Three (out of nine) patients met clinical criteria, and two of them had high serum titre of WNV specific IgM antibodies (3.5 and 5.2). Serum RT-PCR testing was negative. Conformation by neutralization testing was not performed. Both cases represented with encephalitis. None of these cases had recent travel history in WNW endemic areas, or history of blood transfusion and organ transplantation, so they represented autochthonous cases. Although there were no previous reports of flavivirus infections in BiH, described cases had high titre of WNV specific antibodies in serum, and negative flavivirus-vaccination history, they were defined as probable cases because recommended testing for case confirmation was not performed. The West Nile virus should be considered a possible causative pathogen in this area, probably in patients with mild influenza-like disease of unknown origin and those with neuroinvasive disease during late summer and early autumn.

  16. Association of West Nile virus illness and urban landscapes in Chicago and Detroit.

    PubMed

    Ruiz, Marilyn O; Walker, Edward D; Foster, Erik S; Haramis, Linn D; Kitron, Uriel D

    2007-03-12

    West Nile virus infection in humans in urban areas of the Midwestern United States has exhibited strong spatial clustering during epidemic years. We derived urban landscape classes from the physical and socio-economic factors hypothesized to be associated with West Nile Virus (WNV) transmission and compared those to human cases of illness in 2002 in Chicago and Detroit. The objectives were to improve understanding of human exposure to virus-infected mosquitoes in the urban context, and to assess the degree to which environmental factors found to be important in Chicago were also found in Detroit. Five urban classes that partitioned the urban space were developed for each city region. The classes had many similarities in the two settings. In both regions, the WNV case rate was considerably higher in the urban class associated with the Inner Suburbs, where 1940-1960 era housing dominates, vegetation cover is moderate, and population density is moderate. The land cover mapping approach played an important role in the successful and consistent classification of the urban areas. The analysis demonstrates how urban form and past land use decisions can influence transmission of a vector-borne virus. In addition, the results are helpful to develop hypotheses regarding urban landscape features and WNV transmission, they provide a structured method to stratify the urban areas to locate representative field study sites specifically for WNV, and this analysis contributes to the question of how the urban environment affects human health.

  17. Systems immunology reveals markers of susceptibility to West Nile virus infection.

    PubMed

    Qian, Feng; Goel, Gautam; Meng, Hailong; Wang, Xiaomei; You, Fuping; Devine, Lesley; Raddassi, Khadir; Garcia, Melissa N; Murray, Kristy O; Bolen, Christopher R; Gaujoux, Renaud; Shen-Orr, Shai S; Hafler, David; Fikrig, Erol; Xavier, Ramnik; Kleinstein, Steven H; Montgomery, Ruth R

    2015-01-01

    West Nile virus (WNV) infection is usually asymptomatic but can cause severe neurological disease and death, particularly in older patients, and how individual variations in immunity contribute to disease severity is not yet defined. Animal studies identified a role for several immunity-related genes that determine the severity of infection. We have integrated systems-level transcriptional and functional data sets from stratified cohorts of subjects with a history of WNV infection to define whether these markers can distinguish susceptibility in a human population. Transcriptional profiles combined with immunophenotyping of primary cells identified a predictive signature of susceptibility that was detectable years after acute infection (67% accuracy), with the most prominent alteration being decreased IL1B induction following ex vivo infection of macrophages with WNV. Deconvolution analysis also determined a significant role for CXCL10 expression in myeloid dendritic cells. This systems analysis identified markers of pathogenic mechanisms and offers insights into potential therapeutic strategies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. West Nile Virus in Resident Birds from Yucatan, Mexico.

    PubMed

    Chaves, Andrea; Sotomayor-Bonilla, Jesus; Monge, Otto; Ramírez, Abigaíl; Galindo, Francisco; Sarmiento-Silva, Rosa Elena; Gutiérrez-Espeleta, Gustavo A; Suzán, Gerardo

    2016-01-01

    West Nile virus (WNV) in the Americas is thought to be transported at large spatial scales by migratory birds and locally spread and amplified by resident birds. Local processes, including interspecific interactions and dominance of passerine species recognized as competent reservoirs, may boost infection and maintain endemic cycles. Change in species composition has been recognized as an important driver for infection dynamics. Due to migration and changes in species diversity and composition in wintering grounds, changes in infection prevalence are expected. To these changes, we used PCR to estimate the prevalence of WNV in wild resident birds during the dry and rainy seasons of 2012 in Yucatan, Mexico. Serum samples were obtained from 104 wild birds, belonging to six orders and 35 species. We detected WNV in 14 resident birds, representing 11 species and three orders. Prevalences by order was Passeriformes (27%), Columbiformes (6%), and Piciformes (33%). Resident birds positive to WNV from Yucatan may be indicative of local virus circulation and evidence of past virus transmission activity.

  19. West nile virus anti-body surveillance in three Sierra Nevada raptors of conservation concern

    Treesearch

    J.M. Hull; J.J. Keane; L.A. Tell; H.B. Ernest

    2010-01-01

    West Nile virus (WNV) infection has caused high levels of mortality in North American hawks and owls. To investigate the extent of infection among raptors of conservation concern in the Sierra Nevada, we tested 62 Northern Goshawks (Accipiter gentilis), 209 Spotted Owls (Strix occidentalis), and 22 Great Gray Owls (...

  20. West Nile Virus Infection in the Central Nervous System

    PubMed Central

    Winkelmann, Evandro R.; Luo, Huanle; Wang, Tian

    2016-01-01

    West Nile virus (WNV), a neurotropic single-stranded flavivirus has been the leading cause of arboviral encephalitis worldwide.  Up to 50% of WNV convalescent patients in the United States were reported to have long-term neurological sequelae.  Neither antiviral drugs nor vaccines are available for humans.  Animal models have been used to investigate WNV pathogenesis and host immune response in humans.  In this review, we will discuss recent findings from studies in animal models of WNV infection, and provide new insights on WNV pathogenesis and WNV-induced host immunity in the central nervous system. PMID:26918172

  1. Detecting West Nile virus in owls and raptors by an antigen-capture assay.

    PubMed

    Gancz, Ady Y; Campbell, Douglas G; Barker, Ian K; Lindsay, Robbin; Hunter, Bruce

    2004-12-01

    We evaluated a rapid antigen-capture assay (VecTest) for detection of West Nile virus in oropharyngeal and cloacal swabs, collected at necropsy from owls (N = 93) and raptors (N = 27). Sensitivity was 93.5%-95.2% for northern owl species but <42.9% for all other species. Specificity was 100% for owls and 85.7% for raptors.

  2. The impact of West Nile virus on birds in California’s hardwood rangelands

    Treesearch

    Thomas Scott; Pey-Yi Lee; Kerry Paggett; Ryan Carney; Stan Husted; Walter Koenig

    2008-01-01

    West Nile virus has undergone an unprecedented rate of infection in North America, sweeping from New York to California in four years. It attacked an exceptionally broad range of hosts/vectors over a broad geographic area. In 2004, the California Department of Health Services received approximately 98,000 reports of dead birds, representing tens of millions of birds...

  3. West Nile virus circulation in South-Eastern Romania, 2011 to 2013.

    PubMed

    Dinu, S; Cotar, A I; Pănculescu-Gătej, I R; Fălcuţă, E; Prioteasa, F L; Sîrbu, A; Oprişan, G; Bădescu, D; Reiter, P; Ceianu, C S

    2015-05-21

    Lineage 2 West Nile virus (WNV), previously found only in sub-Saharan Africa and Madagascar, was identified in Hungary in 2004 and has rapidly expanded in Europe in the past decade. Following a significant outbreak of West Nile fever with neurological cases caused by lineage 1 WNV in Romania in 1996, scattered cases have been recorded in the south-east of the country in each transmission season. Another outbreak, affecting a larger area and caused by lineage 2 WNV, was recorded in 2010. We analysed human sera from neuroinvasive West Nile fever cases and mosquitoes, sampled in south-eastern Romania between 2011 and 2013, for the presence of WNV genome, and obtained partial NS5 and envelope glycoprotein sequences. Human- and mosquito-derived WNV sequences were highly similar (99%) to Volgograd 2007 lineage 2 WNV and differed from isolates previously detected in central and southern Europe. WNV was detected in one pool of Culex pipiens s.l. males, documenting vertical transmission. Lineage 4 WNV, of unknown pathogenicity to mammals, was found in the amphibian-feeding mosquito Uranotaenia unguiculata from the Danube Delta. Our results present molecular evidence for the maintenance of the same isolates of Volgograd 2007-like lineage 2 WNV in south-eastern Romania between 2011 and 2013.

  4. Hydroclimatic Assessment of West Nile Virus Occurrence Across Continental US

    NASA Astrophysics Data System (ADS)

    Billian, H. E.; Jutla, A.; Colwell, R. R.

    2014-12-01

    West Nile virus (WNV) is the most widely infections from arbovirus in mid-latitudes, having reached the Western Hemisphere in 1999. As a vector-borne disease, WNV is primarily spread by mosquitoes; the disease is predominantly found in tropical and temperate regions of the world, and is now considered an endemic pathogen in the United States, Africa, Asia, Australia, the Middle East, and Europe. Environmental processes play a vital role in the trigger of WNV. Here, using logistical regression models, we quantified relationships between hydroclimatic processes and mosquito abundance for WNV across the continental USA using precipitation and temperature at different spatial and temporal scales. It will be shown that reported cases of this disease are more prevalent during spring and summer months in the entire country, when there is more precipitation and higher surface air temperatures for 2003 to 2013. The key impacts of this research are those related to the improvement of human health, and a means to predict mosquito breeding patterns long term as they relate to the prevalence of vector-borne illnesses.

  5. Predicting Hotspots for Influenza Virus Reassortment

    PubMed Central

    Gilbert, Marius; Martin, Vincent; Cappelle, Julien; Hosseini, Parviez; Njabo, Kevin Y.; Abdel Aziz, Soad; Xiao, Xiangming; Daszak, Peter; Smith, Thomas B.

    2013-01-01

    The 1957 and 1968 influenza pandemics, each of which killed ≈1 million persons, arose through reassortment events. Influenza virus in humans and domestic animals could reassort and cause another pandemic. To identify geographic areas where agricultural production systems are conducive to reassortment, we fitted multivariate regression models to surveillance data on influenza A virus subtype H5N1 among poultry in China and Egypt and subtype H3N2 among humans. We then applied the models across Asia and Egypt to predict where subtype H3N2 from humans and subtype H5N1 from birds overlap; this overlap serves as a proxy for co-infection and in vivo reassortment. For Asia, we refined the prioritization by identifying areas that also have high swine density. Potential geographic foci of reassortment include the northern plains of India, coastal and central provinces of China, the western Korean Peninsula and southwestern Japan in Asia, and the Nile Delta in Egypt. PMID:23628436

  6. West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2014.

    PubMed

    Lindsey, Nicole P; Lehman, Jennifer A; Staples, J Erin; Fischer, Marc

    2015-09-04

    Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States (1). However, several other arboviruses also cause sporadic cases and seasonal outbreaks. This report summarizes surveillance data reported to CDC in 2014 for WNV and other nationally notifiable arboviruses, excluding dengue. Forty-two states and the District of Columbia (DC) reported 2,205 cases of WNV disease. Of these, 1,347 (61%) were classified as WNV neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis), for a national incidence of 0.42 cases per 100,000 population. After WNV, the next most commonly reported cause of arboviral disease was La Crosse virus (80 cases), followed by Jamestown Canyon virus (11), St. Louis encephalitis virus (10), Powassan virus (8), and Eastern equine encephalitis virus (8). WNV and other arboviruses cause serious illness in substantial numbers of persons each year. Maintaining surveillance programs is important to help direct prevention activities.

  7. Context-Dependent Cleavage of the Capsid Protein by the West Nile Virus Protease Modulates the Efficiency of Virus Assembly

    PubMed Central

    VanBlargan, Laura A.; Davis, Kaitlin A.; Dowd, Kimberly A.; Akey, David L.; Smith, Janet L.

    2015-01-01

    ABSTRACT The molecular mechanisms that define the specificity of flavivirus RNA encapsulation are poorly understood. Virions composed of the structural proteins of one flavivirus and the genomic RNA of a heterologous strain can be assembled and have been developed as live attenuated vaccine candidates for several flaviviruses. In this study, we discovered that not all combinations of flavivirus components are possible. While a West Nile virus (WNV) subgenomic RNA could readily be packaged by structural proteins of the DENV2 strain 16681, production of infectious virions with DENV2 strain New Guinea C (NGC) structural proteins was not possible, despite the very high amino acid identity between these viruses. Mutagenesis studies identified a single residue (position 101) of the DENV capsid (C) protein as the determinant for heterologous virus production. C101 is located at the P1′ position of the NS2B/3 protease cleavage site at the carboxy terminus of the C protein. WNV NS2B/3 cleavage of the DENV structural polyprotein was possible when a threonine (Thr101 in strain 16681) but not a serine (Ser101 in strain NGC) occupied the P1′ position, a finding not predicted by in vitro protease specificity studies. Critically, both serine and threonine were tolerated at the P1′ position of WNV capsid. More extensive mutagenesis revealed the importance of flanking residues within the polyprotein in defining the cleavage specificity of the WNV protease. A more detailed understanding of the context dependence of viral protease specificity may aid the development of new protease inhibitors and provide insight into associated patterns of drug resistance. IMPORTANCE West Nile virus (WNV) and dengue virus (DENV) are mosquito-borne flaviviruses that cause considerable morbidity and mortality in humans. No specific antiflavivirus therapeutics are available for treatment of infection. Proteolytic processing of the flavivirus polyprotein is an essential step in the replication

  8. Clinical pathology results from cranes with experimental West Nile Virus infection

    USGS Publications Warehouse

    Olsen, Glenn H.

    2011-01-01

    Sandhill cranes (Grus canadensis) were vaccinated for and then challenged with West Nile virus. Resulting titers demonstrated protection in the vaccinated-challenged cranes as compared to the unvaccinated-challenged cranes. Clinical pathology results showed challenged cranes, whether vaccinated or not, had a decrease in their hematocrits and an elevation of 2.5-fold in their white blood cell counts as compared to unchallenged control sandhill cranes. No differences were apparent in the differential counts of heterophils and lymphocytes.

  9. Reported Neuroinvasive Cases of West Nile Virus by State, 2002-2014

    EPA Pesticide Factsheets

    This map shows the average annual incidence of neuroinvasive West Nile virus disease in each state, which is calculated as the average number of new cases per 100,000 people per year from 2002 to 2014. The map is based on cases that local and state health departments report to CDC??s national disease tracking system. Neuroinvasive cases are those that affect the brain or cause neurologic dysfunction. For more information: www.epa.gov/climatechange/science/indicators

  10. B cell response and mechanisms of antibody protection to West Nile virus.

    PubMed

    Austin, S Kyle; Dowd, Kimberly A

    2014-03-03

    West Nile virus (WNV) has become the principal cause of viral encephalitis in North America since its introduction in New York in 1999. This emerging virus is transmitted to humans via the bite of an infected mosquito. While there have been several candidates in clinical trials, there are no approved vaccines or WNV-specific therapies for the treatment of WNV disease in humans. From studies with small animal models and convalescent human patients, a great deal has been learned concerning the immune response to infection with WNV. Here, we provide an overview of a subset of that information regarding the humoral and antibody response generated during WNV infection.

  11. B Cell Response and Mechanisms of Antibody Protection to West Nile Virus

    PubMed Central

    Austin, S. Kyle; Dowd, Kimberly A.

    2014-01-01

    West Nile virus (WNV) has become the principal cause of viral encephalitis in North America since its introduction in New York in 1999. This emerging virus is transmitted to humans via the bite of an infected mosquito. While there have been several candidates in clinical trials, there are no approved vaccines or WNV-specific therapies for the treatment of WNV disease in humans. From studies with small animal models and convalescent human patients, a great deal has been learned concerning the immune response to infection with WNV. Here, we provide an overview of a subset of that information regarding the humoral and antibody response generated during WNV infection. PMID:24594676

  12. Detecting West Nile Virus in Owls and Raptors by an Antigen-capture Assay

    PubMed Central

    Campbell, Douglas G.; Barker, Ian K.; Lindsay, Robbin; Hunter, Bruce

    2004-01-01

    We evaluated a rapid antigen-capture assay (VecTest) for detection of West Nile virus in oropharyngeal and cloacal swabs, collected at necropsy from owls (N = 93) and raptors (N = 27). Sensitivity was 93.5%–95.2% for northern owl species but <42.9% for all other species. Specificity was 100% for owls and 85.7% for raptors. PMID:15663862

  13. Comparison of Enzootic Risk Measures for Predicting West Nile Disease, Los Angeles, California, USA, 2004–2010

    PubMed Central

    Kwan, Jennifer L.; Park, Bborie K.; Carpenter, Tim E.; Ngo, Van; Civen, Rachel

    2012-01-01

    In Los Angeles, California, USA, 2 epidemics of West Nile virus (WNV) disease have occurred since WNV was recognized in 2003. To assess which measure of risk was most predictive of human cases, we compared 3 measures: the California Mosquito-Borne Virus Surveillance and Response Plan Assessment, the vector index, and the Dynamic Continuous-Area Space-Time system. A case–crossover study was performed by using symptom onset dates from 384 persons with WNV infection to determine their relative environmental exposure to high-risk conditions as measured by each method. Receiver-operating characteristic plots determined thresholds for each model, and the area under the curve was used to compare methods. We found that the best risk assessment model for human WNV cases included surveillance data from avian, mosquito, and climate sources. PMID:22840314

  14. Identification of Suitable Areas for West Nile Virus Circulation in Tunisia.

    PubMed

    Ben Hassine, T; Conte, A; Calistri, P; Candeloro, L; Ippoliti, C; De Massis, F; Danzetta, M L; Bejaoui, M; Hammami, S

    2017-04-01

    West Nile virus (WNV) is a mosquito-transmitted Flavivirus belonging to the Japanese encephalitis antigenic complex of the Flaviviridae family. It is transmitted primarily by the bite of infected mosquitoes, particularly Culex spp. and Aedes/Ochlerotatus spp., which acquire the virus by feeding on viraemic birds. Humans, horses and other mammals are regarded as incidental or dead-end hosts. In the last decades, an increasing number of cases of WNV infection in horses and humans have been notified in the Mediterranean basin. In Tunisia, human cases of WNV-related meningoencephalitis were detected in 1997, 2003, 2007, 2010, 2011 and 2012. Based on the analysis of climatic and environmental conditions found in the locations where human cases have been reported in 2012, the aim of this study was to identify similar areas in Tunisia potentially at risk of disease occurrence. Data related to 85 neuroinvasive West Nile fever (WNF) human cases were georeferenced and a set of environmental and climatic variables (wetlands and humid areas, normalized difference vegetation index (NDVI), temperatures and elevation, migratory bird settlements) were used in the analysis. Areas, ecologically similar to those where human cases were detected, were identified using the Mahalanobis distance statistic. A leave-one-out cross-validation was performed to validate the sensitivity of the model, and 78 of 85 points were correctly classified. © 2015 Blackwell Verlag GmbH.

  15. Development and validation of a climate-based ensemble prediction model for West Nile Virus infection rates in Culex mosquitoes, Suffolk County, New York.

    PubMed

    Little, Eliza; Campbell, Scott R; Shaman, Jeffrey

    2016-08-09

    West Nile Virus (WNV) is an endemic public health concern in the United States that produces periodic seasonal epidemics. Underlying these outbreaks is the enzootic cycle of WNV between mosquito vectors and bird hosts. Identifying the key environmental conditions that facilitate and accelerate this cycle can be used to inform effective vector control. Here, we model and forecast WNV infection rates among mosquito vectors in Suffolk County, New York using readily available meteorological and hydrological conditions. We first validate a statistical model built with surveillance data between 2001 and 2009 (m09) and specify a set of new statistical models using surveillance data from 2001 to 2012 (m12). This ensemble of new models is then used to make predictions for 2013-2015, and multimodel inference is employed to provide a formal probabilistic interpretation across the disparate individual model predictions. The findings of the m09 and m12 models align; with the ensemble of m12 models indicating an association between warm, dry early spring (April) conditions and increased annual WNV infection rates in Culex mosquitoes. This study shows that real-time climate information can be used to predict WNV infection rates in Culex mosquitoes prior to its seasonal peak and before WNV spillover transmission risk to humans is greatest.

  16. Zika virus infection confers protection against West Nile virus challenge in mice

    PubMed Central

    Vázquez-Calvo, Ángela; Blázquez, Ana-Belén; Escribano-Romero, Estela; Merino-Ramos, Teresa; Saiz, Juan-Carlos; Martín-Acebes, Miguel A; Jiménez de Oya, Nereida

    2017-01-01

    Flaviviruses are RNA viruses that constitute a worrisome threat to global human and animal health. Zika virus (ZIKV), which was initially reported to cause a mild disease, recently spread in the Americas, infecting millions of people. During this recent epidemic, ZIKV infection has been linked to serious neurological diseases and birth defects, specifically Guillain-Barrè syndrome (GBS) and microcephaly. Because information about ZIKV immunity remains scarce, we assessed the humoral response of immunocompetent mice to infection with three viral strains of diverse geographical origin (Africa, Asia and America). No infected animals showed any sign of disease or died after infection. However, specific neutralizing antibodies were elicited in all infected mice. Considering the rapid expansion of ZIKV throughout the American continent and its co-circulation with other medically relevant flaviviruses, such as West Nile virus (WNV), the induction of protective immunity between ZIKV and WNV was analyzed. Remarkably, protection after challenge with WNV was observed in mice previously infected with ZIKV, as survival rates were significantly higher than in control mice. Moreover, previous ZIKV infection enhanced the humoral immune response against WNV. These findings may be relevant in geographical areas where both ZIKV and WNV co-circulate, as well as for the future development of broad-spectrum flavivirus vaccines. PMID:28928416

  17. Zika virus infection confers protection against West Nile virus challenge in mice.

    PubMed

    Vázquez-Calvo, Ángela; Blázquez, Ana-Belén; Escribano-Romero, Estela; Merino-Ramos, Teresa; Saiz, Juan-Carlos; Martín-Acebes, Miguel A; Jiménez de Oya, Nereida

    2017-09-20

    Flaviviruses are RNA viruses that constitute a worrisome threat to global human and animal health. Zika virus (ZIKV), which was initially reported to cause a mild disease, recently spread in the Americas, infecting millions of people. During this recent epidemic, ZIKV infection has been linked to serious neurological diseases and birth defects, specifically Guillain-Barrè syndrome (GBS) and microcephaly. Because information about ZIKV immunity remains scarce, we assessed the humoral response of immunocompetent mice to infection with three viral strains of diverse geographical origin (Africa, Asia and America). No infected animals showed any sign of disease or died after infection. However, specific neutralizing antibodies were elicited in all infected mice. Considering the rapid expansion of ZIKV throughout the American continent and its co-circulation with other medically relevant flaviviruses, such as West Nile virus (WNV), the induction of protective immunity between ZIKV and WNV was analyzed. Remarkably, protection after challenge with WNV was observed in mice previously infected with ZIKV, as survival rates were significantly higher than in control mice. Moreover, previous ZIKV infection enhanced the humoral immune response against WNV. These findings may be relevant in geographical areas where both ZIKV and WNV co-circulate, as well as for the future development of broad-spectrum flavivirus vaccines.

  18. West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2016.

    PubMed

    Burakoff, Alexis; Lehman, Jennifer; Fischer, Marc; Staples, J Erin; Lindsey, Nicole P

    2018-01-12

    Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the continental United States (1,2). Other arboviruses, including La Crosse, Powassan, Jamestown Canyon, St. Louis encephalitis, and eastern equine encephalitis viruses, cause sporadic cases of disease and occasional outbreaks. This report summarizes surveillance data reported to CDC for 2016 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses, as these are primarily nondomestic viruses typically acquired through travel. Forty-seven states and the District of Columbia (DC) reported 2,240 cases of domestic arboviral disease, including 2,150 (96%) WNV disease cases. Of the WNV disease cases, 1,310 (61%) were classified as neuroinvasive disease (e.g., meningitis, encephalitis, acute flaccid paralysis), for a national incidence of 0.41 cases per 100,000 population. After WNV, the most frequently reported arboviruses were La Crosse (35 cases), Powassan (22), and Jamestown Canyon (15) viruses. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct prevention activities.

  19. A thiopurine drug inhibits West Nile virus production in cell culture, but not in mice.

    PubMed

    Lim, Pei-Yin; Keating, Julie A; Hoover, Spencer; Striker, Rob; Bernard, Kristen A

    2011-01-01

    Many viruses within the Flavivirus genus cause significant disease in humans; however, effective antivirals against these viruses are not currently available. We have previously shown that a thiopurine drug, 6-methylmercaptopurine riboside (6MMPr), inhibits replication of distantly related viruses within the Flaviviridae family in cell culture, including bovine viral diarrhea virus and hepatitis C virus replicon. Here we further examined the potential antiviral effect of 6MMPr on several diverse flaviviruses. In cell culture, 6MMPr inhibited virus production of yellow fever virus, dengue virus-2 (DENV-2) and West Nile virus (WNV) in a dose-dependent manner, and DENV-2 was significantly more sensitive to 6MMPr treatment than WNV. We then explored the use of 6MMPr as an antiviral against WNV in an immunocompetent mouse model. Once a day treatment of mice with 0.5 mg 6MMPr was just below the toxic dose in our mouse model, and this dose was used in subsequent studies. Mice were treated with 6MMPr immediately after subcutaneous inoculation with WNV for eight consecutive days. Treatment with 6MMPr exacerbated weight loss in WNV-inoculated mice and did not significantly affect mortality. We hypothesized that 6MMPr has low bioavailability in the central nervous system (CNS) and examined the effect of pre-treatment with 6MMPr on viral loads in the periphery and CNS. Pre-treatment with 6MMPr had no significant effect on viremia or viral titers in the periphery, but resulted in significantly higher viral loads in the brain, suggesting that the effect of 6MMPr is tissue-dependent. In conclusion, despite being a potent inhibitor of flaviviruses in cell culture, 6MMPr was not effective against West Nile disease in mice; however, further studies are warranted to reduce the toxicity and/or improve the bioavailability of this potential antiviral drug.

  20. A rapid and quantitative assay for measuring antibody-mediated neutralization of West Nile virus infection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pierson, Theodore C.; Sanchez, Melissa D.; Puffer, Bridget A.

    2006-03-01

    West Nile virus (WNV) is a neurotropic flavivirus within the Japanese encephalitis antigenic complex that is responsible for causing West Nile encephalitis in humans. The surface of WNV virions is covered by a highly ordered icosahedral array of envelope proteins that is responsible for mediating attachment and fusion with target cells. These envelope proteins are also primary targets for the generation of neutralizing antibodies in vivo. In this study, we describe a novel approach for measuring antibody-mediated neutralization of WNV infection using virus-like particles that measure infection as a function of reporter gene expression. These reporter virus particles (RVPs) aremore » produced by complementation of a sub-genomic replicon with WNV structural proteins provided in trans using conventional DNA expression vectors. The precision and accuracy of this approach stem from an ability to measure the outcome of the interaction between antibody and viral antigens under conditions that satisfy the assumptions of the law of mass action as applied to virus neutralization. In addition to its quantitative strengths, this approach allows the production of WNV RVPs bearing the prM-E proteins of different WNV strains and mutants, offering considerable flexibility for the study of the humoral immune response to WNV in vitro. WNV RVPs are capable of only a single round of infection, can be used under BSL-2 conditions, and offer a rapid and quantitative approach for detecting virus entry and its inhibition by neutralizing antibody.« less

  1. Ovicidal and larvicidal effects of garlic and asafoetida essential oils against West Nile virus vectors

    USDA-ARS?s Scientific Manuscript database

    We examined the chemical composition of garlic and asafoetida essential oils and their individual and combined toxicity against larvae of two West Nile virus vectors, Culex pipiens pipiens and Cx. restuans. The effect of the two essential oils on egg hatch was also examined. Ten and twelve compounds...

  2. Mechanism of West Nile Virus Neuroinvasion: A Critical Appraisal

    PubMed Central

    Suen, Willy W.; Prow, Natalie A.; Hall, Roy A.; Bielefeldt-Ohmann, Helle

    2014-01-01

    West Nile virus (WNV) is an important emerging neurotropic virus, responsible for increasingly severe encephalitis outbreaks in humans and horses worldwide. However, the mechanism by which the virus gains entry to the brain (neuroinvasion) remains poorly understood. Hypotheses of hematogenous and transneural entry have been proposed for WNV neuroinvasion, which revolve mainly around the concepts of blood-brain barrier (BBB) disruption and retrograde axonal transport, respectively. However, an over‑representation of in vitro studies without adequate in vivo validation continues to obscure our understanding of the mechanism(s). Furthermore, WNV infection in the current rodent models does not generate a similar viremia and character of CNS infection, as seen in the common target hosts, humans and horses. These differences ultimately question the applicability of rodent models for pathogenesis investigations. Finally, the role of several barriers against CNS insults, such as the blood-cerebrospinal fluid (CSF), the CSF-brain and the blood-spinal cord barriers, remain largely unexplored, highlighting the infancy of this field. In this review, a systematic and critical appraisal of the current evidence relevant to the possible mechanism(s) of WNV neuroinvasion is conducted. PMID:25046180

  3. A Hierarchical Approach Embedding Hydrologic and Population Modeling for a West Nile Virus Vector Prediction

    NASA Astrophysics Data System (ADS)

    Jian, Y.; Silvestri, S.; Marani, M.; Saltarin, A.; Chillemi, G.

    2012-12-01

    We applied a hierarchical state space model to predict the abundance of Cx.pipiens (a West Nile Virus vector) in the Po River Delta Region, Northeastern Italy. The study area has large mosquito abundance, due to a favorable environment and climate as well as dense human population. Mosquito data were collected on a weekly basis at more than 20 sites from May to September in 2010 and 2011. Cx.pipiens was the dominant species in our samples, accounting for about 90% of the more than 300,000 total captures. The hydrological component of the model accounted for evapotranspiration, infiltration and deep percolation to infer, in a 0D context, the local dynamics of soil moisture as a direct exogenous forcing of mosquito dynamics. The population model had a Gompertz structure, which included exogenous meteorological forcings and delayed internal dynamics. The models were coupled within a hierarchical statistical structure to overcome the relatively short length of the samples by exploiting the large number of concurrent observations available. The results indicated that Cx.pipiens abundance had significant density dependence at 1 week lag, which approximately matched its development time from larvae to adult. Among the exogenous controls, temperature, daylight hours, and soil moisture explained most of the dynamics. Longer daylight hours and lower soil moisture values resulted in higher abundance. The negative correlation of soil moisture and mosquito population can be explained with the abundance of water in the region (e.g. due to irrigation) and the preference for eutrophic habitats by Cx.pipien. Variations among sites were explained by land use factors as represented by distance to the nearest rice field and NDVI values: the carrying capacity decreased with increased distance to the nearest rice filed, while the maximum growth rate was positively related with NDVI. The model shows a satisfactory performance in predicting (potentially one week in advance) mosquito

  4. Identification of environmental covariates of West Nile virus vector mosquito population abundance.

    PubMed

    Trawinski, Patricia R; Mackay, D Scott

    2010-06-01

    The rapid spread of West Nile virus (WNv) in North America is a major public health concern. Culex pipiens-restuans is the principle mosquito vector of WNv in the northeastern United States while Aedes vexans is an important bridge vector of the virus in this region. Vector mosquito abundance is directly dependent on physical environmental factors that provide mosquito habitats. The objective of this research is to determine landscape elements that explain the population abundance and distribution of WNv vector mosquitoes using stepwise linear regression. We developed a novel approach for examining a large set of landscape variables based on a land use and land cover classification by selecting variables in stages to minimize multicollinearity. We also investigated the distance at which landscape elements influence abundance of vector populations using buffer distances of 200, 400, and 1000 m. Results show landscape effects have a significant impact on Cx. pipiens-estuans population distribution while the effects of landscape features are less important for prediction of Ae. vexans population distributions. Cx. pipiens-restuans population abundance is positively correlated with human population density, housing unit density, and urban land use and land cover classes and negatively correlated with age of dwellings and amount of forested land.

  5. A geospatial study of the potential of two exotic species of mosquitoes to impact the epidemiology of West Nile virus in Maryland.

    PubMed

    Kutz, Frederick W; Wade, Timothy G; Pagac, Benedict B

    2003-09-01

    We used geospatial techniques to study the potential impact of 2 exotic mosquitoes, Aedes albopictus and Ochlerotatus japonicus japonicus, on the epidemiology of West Nile virus in Maryland. These 2 species have established populations in Maryland over the past 15 years. Larvae of both mosquito species are found in natural and artificial water-holding cavities and containers, particularly water in tires. Therefore, we used locations of licensed tire dealers and of tire dumps scheduled for clean up as an index for potential sources of mosquito vectors. This index was expected to underestimate the actual population of source habitats. West Nile virus activity in Maryland during 1999, 2000, and 2001 was indicated by the presence of dead, infected birds, particularly American crows and other corvids; infected pools of mosquitoes; and human and horse infections. Adult females of both mosquito species are aggressive, opportunistic feeders that have been observed to take blood meals from avian and mammalian hosts. Susceptible vertebrate hosts, particularly birds, are ubiquitously distributed throughout the developed areas of the state. This analysis demonstrated a spatial convergence of the virus, the exotic mosquito vectors, and susceptible hosts. This conjunction indicated that these 2 mosquito species have a high potential to serve as bridge vectors and thus, impact the epidemiology of West Nile virus under favorable environmental and climatic conditions. Positive mosquito pools were collected from only the Baltimore-Washington metropolitan corridor, suggesting a newly created enzootic focus for this virus. Land-cover analysis of the sites where virus activity had been detected showed predominantly developed land uses. Analyses of the environmental justice aspects (social, economic, and housing characteristics) of block groups with human West Nile fever cases or with positive mosquito pools were equivocal. Human cases seemed to occur in developed block groups with

  6. Chemiluminescent optical fiber immunosensor for the detection of anti-West Nile virus IgG.

    PubMed

    Herrmann, Sebastien; Leshem, Boaz; Landes, Shimi; Rager-Zisman, Bracha; Marks, Robert S

    2005-03-31

    An ELISA-based optical fiber methodology developed for the detection of anti-West Nile virus IgG antibodies in serum was compared to standard colorimetric and chemiluminescent ELISA based on microtiter plates. Colorimetric ELISA was the least sensitive, especially at high titer dilutions. The fiber-optic immunosensor based on the same ELISA immunological rationale was the most sensitive technique.

  7. The West Nile Virus-Like Flavivirus Koutango Is Highly Virulent in Mice due to Delayed Viral Clearance and the Induction of a Poor Neutralizing Antibody Response

    PubMed Central

    Setoh, Yin X.; Biron, Rebecca M.; Sester, David P.; Kim, Kwang Sik; Hobson-Peters, Jody; Hall, Roy A.; Bielefeldt-Ohmann, Helle

    2014-01-01

    ABSTRACT The mosquito-borne West Nile virus (WNV) is responsible for outbreaks of viral encephalitis in humans, horses, and birds, with particularly virulent strains causing recent outbreaks of disease in eastern Europe, the Middle East, North America, and Australia. Previous studies have phylogenetically separated WNV strains into two main genetic lineages (I and II) containing virulent strains associated with neurological disease. Several WNV-like strains clustering outside these lineages have been identified and form an additional five proposed lineages. However, little is known about whether these strains have the potential to induce disease. In a comparative analysis with the highly virulent lineage I American strain (WNVNY99), the low-pathogenicity lineage II strain (B956), a benign Australian strain, Kunjin (WNVKUN), the African WNV-like Koutango virus (WNVKOU), and a WNV-like isolate from Sarawak, Malaysia (WNVSarawak), were assessed for neuroinvasive properties in a murine model and for their replication kinetics in vitro. While WNVNY99 replicated to the highest levels in vitro, in vivo mouse challenge revealed that WNVKOU was more virulent, with a shorter time to onset of neurological disease and higher morbidity. Histological analysis of WNVKOU- and WNVNY99-infected brain and spinal cords demonstrated more prominent meningoencephalitis and the presence of viral antigen in WNVKOU-infected mice. Enhanced virulence of WNVKOU also was associated with poor viral clearance in the periphery (sera and spleen), a skewed innate immune response, and poor neutralizing antibody development. These data demonstrate, for the first time, potent neuroinvasive and neurovirulent properties of a WNV-like virus outside lineages I and II. IMPORTANCE In this study, we characterized the in vitro and in vivo properties of previously uncharacterized West Nile virus strains and West Nile-like viruses. We identified a West Nile-like virus, Koutango virus (WNVKOU), that was more

  8. West Nile virus disease: a descriptive study of 228 patients hospitalized in a 4-county region of Colorado in 2003.

    PubMed

    Bode, Amy V; Sejvar, James J; Pape, W John; Campbell, Grant L; Marfin, Anthony A

    2006-05-01

    Risk factors for complications of West Nile virus disease and prognosis in hospitalized patients are incompletely understood. Demographic characteristics and data regarding potential risk factors, hospitalization, and dispositions were abstracted from medical records for residents of 4 Colorado counties who were hospitalized in 2003 with West Nile virus disease. Univariate and multivariate analyses were used to identify factors associated with West Nile encephalitis (WNE), limb weakness, or death by comparing factors among persons with the outcome of interest with factors among those without the outcome of interest. Medical records of 221 patients were reviewed; 103 had West Nile meningitis, 65 had WNE, and 53 had West Nile fever. Respiratory failure, limb weakness, and cardiac arrhythmia occurred in all groups, with significantly more cases of each in the WNE group. Age, alcohol abuse, and diabetes were associated with WNE. Age and WNE were associated with limb weakness. The mortality rate in the WNE group was 18%; age, immunosuppression, requirement of mechanical ventilation, and history of stroke were associated with death. Only 21% of patients with WNE who survived returned to a prehospitalization level of function. The estimated incidence of West Nile fever cases that required hospitalization was 6.0 cases per 100,000 persons; West Nile fever was associated with arrhythmia, limb weakness, and respiratory failure. Persons with diabetes and a reported history of alcohol abuse and older persons appear to be at increased risk of developing WNE. Patients with WNE who have a history of stroke, who require mechanical ventilation, or who are immunosuppressed appear to be more likely to die. Respiratory failure, limb weakness, and arrhythmia occurred in all 3 categories, but there were significantly more cases of all in the WNE group.

  9. West Nile virus-neutralizing antibodies in wild birds from southern Spain.

    PubMed

    Ferraguti, M; LA Puente, J Martínez-DE; Soriguer, R; Llorente, F; Jiménez-Clavero, M Á; Figuerola, J

    2016-07-01

    West Nile virus (WNV) is an emerging vector-borne arbovirus with a zoonotic life-cycle whose main reservoir hosts are birds. In humans and horses, WNV infections rarely result in clinical disease but on occasions - depending on factors such as climatic conditions, insect communities and background immunity levels in local populations - they can lead to outbreaks that threaten public and animal health. We tested for the presence of WNV antibodies in 149 birds belonging to 32 different species. Samples were first tested using a bird-specific ELISA kit and then both positive and doubtful results were confirmed by neutralization tests using WNV and Usutu virus. WNV antibodies were confirmed in a resident Sylvia melanocephala juvenile, supporting the idea of local transmission of WNV in southern Spain in 2013. In addition, the serum from an adult blackbird (Turdus merula) showed neutralization of both WNV and Usutu virus. We discuss our results in light of the occurrence of WNV on horse farms in southern Spain in 2013.

  10. West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2015.

    PubMed

    Krow-Lucal, Elisabeth; Lindsey, Nicole P; Lehman, Jennifer; Fischer, Marc; Staples, J Erin

    2017-01-20

    Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. The leading cause of domestically acquired arboviral disease in the United States is West Nile virus (WNV) (1). Other arboviruses, including La Crosse, St. Louis encephalitis, Jamestown Canyon, Powassan, and eastern equine encephalitis viruses, also cause sporadic cases and outbreaks. This report summarizes surveillance data reported to CDC in 2015 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses, which are primarily nondomestic viruses typically acquired through travel (and are addressed in other CDC reports). In 2015, 45 states and the District of Columbia (DC) reported 2,282 cases of domestic arboviral disease. Among these cases, 2,175 (95%) were WNV disease and 1,455 (67%) of those were classified as neuroinvasive disease (meningitis, encephalitis, or acute flaccid paralysis). The national incidence of WNV neuroinvasive disease was 0.45 cases per 100,000 population. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct prevention activities such as reduction of vector populations and screening of blood donors.

  11. Identification of five interferon-induced cellular proteins that inhibit west nile virus and dengue virus infections.

    PubMed

    Jiang, Dong; Weidner, Jessica M; Qing, Min; Pan, Xiao-Ben; Guo, Haitao; Xu, Chunxiao; Zhang, Xianchao; Birk, Alex; Chang, Jinhong; Shi, Pei-Yong; Block, Timothy M; Guo, Ju-Tao

    2010-08-01

    Interferons (IFNs) are key mediators of the host innate antiviral immune response. To identify IFN-stimulated genes (ISGs) that instigate an antiviral state against two medically important flaviviruses, West Nile virus (WNV) and dengue virus (DENV), we tested 36 ISGs that are commonly induced by IFN-alpha for antiviral activity against the two viruses. We discovered that five ISGs efficiently suppressed WNV and/or DENV infection when they were individually expressed in HEK293 cells. Mechanistic analyses revealed that two structurally related cell plasma membrane proteins, IFITM2 and IFITM3, disrupted early steps (entry and/or uncoating) of the viral infection. In contrast, three IFN-induced cellular enzymes, viperin, ISG20, and double-stranded-RNA-activated protein kinase, inhibited steps in viral proteins and/or RNA biosynthesis. Our results thus imply that the antiviral activity of IFN-alpha is collectively mediated by a panel of ISGs that disrupt multiple steps of the DENV and WNV life cycles.

  12. West Nile virus: A re-emerging pathogen revisited

    PubMed Central

    Martín-Acebes, Miguel A; Saiz, Juan-Carlos

    2012-01-01

    West Nile virus (WNV), a flavivirus of the Flaviviridae family, is maintained in nature in an enzootic transmission cycle between avian hosts and ornithophilic mosquito vectors, although the virus occasionally infects other vertebrates. WNV causes sporadic disease outbreaks in horses and humans, which may result in febrile illness, meningitis, encephalitis and flaccid paralysis. Until recently, its medical and veterinary health concern was relatively low; however, the number, frequency and severity of outbreaks with neurological consequences in humans and horses have lately increased in Europe and the Mediterranean basin. Since its introduction in the Americas, the virus spread across the continent with worrisome consequences in bird mortality and a considerable number of outbreaks among humans and horses, which have resulted in the largest epidemics of neuroinvasive WNV disease ever documented. Surprisingly, its incidence in human and animal health is very different in Central and South America, and the reasons for it are not yet understood. Even though great advances have been obtained lately regarding WNV infection, and although efficient equine vaccines are available, no specific treatments or vaccines for human use are on the market. This review updates the most recent investigations in different aspects of WNV life cycle: molecular virology, transmission dynamics, host range, clinical presentations, epidemiology, ecology, diagnosis, control, and prevention, and highlights some aspects that certainly require further research. PMID:24175211

  13. Mosquito species involved in the circulation of West Nile and Usutu viruses in Italy.

    PubMed

    Mancini, Giuseppe; Montarsi, Fabrizio; Calzolari, Mattia; Capelli, Gioia; Dottori, Michele; Ravagnan, Silvia; Lelli, Davide; Chiari, Mario; Santilli, Adriana; Quaglia, Michela; Quaglia, Michela; Federici, Valentina; Monaco, Federica; Goffredo, Maria; Savini, Giovanni

    2017-06-30

    Usutu (USUV) and West Nile (WNV) are mosquito-borne Flavivirus emerged in Italy in 1996 and 1998, respectively, and reappeared 10 years later. The aim of this work is to review the Italian mosquito species found positive for WNV and USUV between 2008 and 2014. Moreover, the role of mosquitoes in promoting the overwintering of these viruses is discussed, as a result of the mosquito collections performed in Molise region between September 2010 and April 2011. Overall 99,000 mosquitoes were collected: 337 and 457 mosquito pools tested positive by real time reverse transcriptase polymerase chain reaction (real time RT-PCR) for WNV and USUV, respectively. West Nile virus was detected in pools of Culex pipiens s.l. (329), Ochlerotatus caspius (4), Culex modestus (2), and Culex spp. (2). Positive USUV pools were from Cx. pipiens s.l. (435), Aedes albopictus (12), Oc. caspius (5), Culex spp. (2), Anopheles maculipennis s.l. (1), Culiseta annulata (1), and Ochlerotatus detritus (1). In Molise region, 1,694 mosquitoes were collected, and USUV was identi ed in Cx. pipiens s.l., Cs. annulata, and Oc. detritus pools. This paper shows that Cx. pipiens s.l. is the mosquito species most involved in the WNV and USUV circulation in Italy, although other species would also support the spread of both the viruses during Winter.

  14. A review of the vector management methods to prevent and control outbreaks of West Nile virus infection and the challenge for Europe

    PubMed Central

    2014-01-01

    West Nile virus infection is a growing concern in Europe. Vector management is often the primary option to prevent and control outbreaks of the disease. Its implementation is, however, complex and needs to be supported by integrated multidisciplinary surveillance systems and to be organized within the framework of predefined response plans. The impact of the vector control measures depends on multiple factors and the identification of the best combination of vector control methods is therefore not always straightforward. Therefore, this contribution aims at critically reviewing the existing vector control methods to prevent and control outbreaks of West Nile virus infection and to present the challenges for Europe. Most West Nile virus vector control experiences have been recently developed in the US, where ecological conditions are different from the EU and vector control is organized under a different regulatory frame. The extrapolation of information produced in North America to Europe might be limited because of the seemingly different epidemiology in the European region. Therefore, there is an urgent need to analyse the European experiences of the prevention and control of outbreaks of West Nile virus infection and to perform robust cost-benefit analysis that can guide the implementation of the appropriate control measures. Furthermore, to be effective, vector control programs require a strong organisational backbone relying on a previously defined plan, skilled technicians and operators, appropriate equipment, and sufficient financial resources. A decision making guide scheme is proposed which may assist in the process of implementation of vector control measures tailored on specific areas and considering the available information and possible scenarios. PMID:25015004

  15. West Nile virus--neutralizing antibodies in humans in Greece.

    PubMed

    Papa, Anna; Perperidou, Parthena; Tzouli, Anisa; Castilletti, Concetta

    2010-10-01

    Serum samples collected during March-May 2007 from 392 residents of Imathia prefecture, Northern Greece, were tested by indirect immunofluorescence assay and enzyme-linked immunosorbent assay for IgG antibodies against West Nile virus (WNV). Microneutralization assay was applied in six positive samples. Four (4/392, 1.02%) were found positive for WNV-neutralizing antibodies. None of the positive individuals had a history of travel in endemic area or flavivirus vaccination, suggesting that WNV, or an antigenically related flavivirus, circulates in an endemic sylvatic cycle, at least locally, in rural areas in Greece. Human, animal, and vector surveillance systems have to be implemented to provide an early detection of WNV activity in Greece.

  16. Occurrence of west nile virus infection in raptors at the Salton Sea, California.

    PubMed

    Dusek, Robert J; Iko, William M; Hofmeister, Erik K

    2010-07-01

    We investigated the prevalence of West Nile virus (WNV)-neutralizing antibodies and infectious virus, and the occurrence of overwinter transmission in two raptor species during January and March 2006 at the Salton Sea, Imperial County, California. We captured 208 American Kestrels (Falco sparverius) (January, n=100; March, n=108) and 116 Burrowing Owls (Athene cunicularia) (January, n=52; March, n=64). Laboratory analysis revealed that 83% of American Kestrels and 31% of Burrowing Owls were positive for WNV-neutralizing antibodies. Additionally, two seroconversions were detected in Burrowing Owls between January and March. Infectious WNV, consistent with acute infection, was not detected in any bird.

  17. Occurrence of West Nile virus infection in raptors at the Salton Sea, California

    USGS Publications Warehouse

    Dusek, Robert J.; Iko, William M.; Hofmeister, Erik K.

    2010-01-01

    We investigated the prevalence of West Nile virus (WNV)-neutralizing antibodies and infectious virus, and the occurrence of overwinter transmission in two raptor species during January and March 2006 at the Salton Sea, Imperial County, California. We captured 208 American Kestrels (Falco sparverius) (January, n=100; March, n=108) and 116 Burrowing Owls (Athene cunicularia) (January, n=52; March, n=64). Laboratory analysis revealed that 83% of American Kestrels and 31% of Burrowing Owls were positive for WNV-neutralizing antibodies. Additionally, two seroconversions were detected in Burrowing Owls between January and March. Infectious WNV, consistent with acute infection, was not detected in any bird.

  18. Context-Dependent Cleavage of the Capsid Protein by the West Nile Virus Protease Modulates the Efficiency of Virus Assembly.

    PubMed

    VanBlargan, Laura A; Davis, Kaitlin A; Dowd, Kimberly A; Akey, David L; Smith, Janet L; Pierson, Theodore C

    2015-08-01

    The molecular mechanisms that define the specificity of flavivirus RNA encapsulation are poorly understood. Virions composed of the structural proteins of one flavivirus and the genomic RNA of a heterologous strain can be assembled and have been developed as live attenuated vaccine candidates for several flaviviruses. In this study, we discovered that not all combinations of flavivirus components are possible. While a West Nile virus (WNV) subgenomic RNA could readily be packaged by structural proteins of the DENV2 strain 16681, production of infectious virions with DENV2 strain New Guinea C (NGC) structural proteins was not possible, despite the very high amino acid identity between these viruses. Mutagenesis studies identified a single residue (position 101) of the DENV capsid (C) protein as the determinant for heterologous virus production. C101 is located at the P1' position of the NS2B/3 protease cleavage site at the carboxy terminus of the C protein. WNV NS2B/3 cleavage of the DENV structural polyprotein was possible when a threonine (Thr101 in strain 16681) but not a serine (Ser101 in strain NGC) occupied the P1' position, a finding not predicted by in vitro protease specificity studies. Critically, both serine and threonine were tolerated at the P1' position of WNV capsid. More extensive mutagenesis revealed the importance of flanking residues within the polyprotein in defining the cleavage specificity of the WNV protease. A more detailed understanding of the context dependence of viral protease specificity may aid the development of new protease inhibitors and provide insight into associated patterns of drug resistance. West Nile virus (WNV) and dengue virus (DENV) are mosquito-borne flaviviruses that cause considerable morbidity and mortality in humans. No specific antiflavivirus therapeutics are available for treatment of infection. Proteolytic processing of the flavivirus polyprotein is an essential step in the replication cycle and is an attractive

  19. Current Trends in West Nile Virus Vaccine Development

    PubMed Central

    Amanna, Ian J.; Slifka, Mark K.

    2014-01-01

    West Nile virus (WNV) is a mosquito-borne flavivirus that has become endemic in the United States. From 1999-2012, there have been 37,088 reported cases of WNV and 1,549 deaths, resulting in a 4.2% case-fatality rate. Despite development of effective WNV vaccines for horses, there is no vaccine to prevent human WNV infection. Several vaccines have been tested in preclinical studies and to date there have been 8 clinical trials, with promising results in terms of safety and induction of antiviral immunity. Although mass vaccination is unlikely to be cost-effective, implementation of a targeted vaccine program may be feasible if a safe and effective vaccine can be brought to market. Further evaluation of new and advanced vaccine candidates is strongly encouraged. PMID:24689659

  20. Serosurvey Reveals Exposure to West Nile Virus in Asymptomatic Horse Populations in Central Spain Prior to Recent Disease Foci.

    PubMed

    Abad-Cobo, A; Llorente, F; Barbero, M Del Carmen; Cruz-López, F; Forés, P; Jiménez-Clavero, M Á

    2017-10-01

    West Nile fever/encephalitis (WNF) is an infectious disease affecting horses, birds and humans, with a cycle involving birds as natural reservoirs and mosquitoes as transmission vectors. It is a notifiable disease, re-emerging in Europe. In Spain, it first appeared in horses in the south (Andalusia) in 2010, where outbreaks occur every year since. However, in 2014, an outbreak was declared in horses in central Spain, approximately 200 km away from the closest foci in Andalusia. Before that, evidence of West Nile virus (WNV) circulation in central Spain had been obtained only from wildlife, but never in horses. The purpose of this work was to perform a serosurvey to retrospectively detect West Nile virus infections in asymptomatic horses in central Spain from 2011 to 2013, that is before the occurrence of the first outbreaks in the area. For that, serum samples from 369 horses, collected between September 2011 and November 2013 in central Spain, were analysed by ELISA (blocking and IgM) and confirmed by virus neutralization, proving its specificity using parallel titration with another flavivirus (Usutu virus). As a result, 10 of 369 horse serum samples analysed gave positive results by competitive ELISA, 5 of which were confirmed as positive to WNV by virus neutralization (seropositivity rate: 1.35%). One of these WNV seropositive samples was IgM-positive. Chronologically, the first positive samples, including the IgM-positive, corresponded to sera collected in 2012 in Madrid province. From these results, we concluded that WNV circulated in asymptomatic equine populations of central Spain at least since 2012, before the first disease outbreak reported in this area. © 2016 Blackwell Verlag GmbH.

  1. Acute West Nile Virus Meningoencephalitis Diagnosed Via Metagenomic Deep Sequencing of Cerebrospinal Fluid in a Renal Transplant Patient.

    PubMed

    Wilson, M R; Zimmermann, L L; Crawford, E D; Sample, H A; Soni, P R; Baker, A N; Khan, L M; DeRisi, J L

    2017-03-01

    Solid organ transplant patients are vulnerable to suffering neurologic complications from a wide array of viral infections and can be sentinels in the population who are first to get serious complications from emerging infections like the recent waves of arboviruses, including West Nile virus, Chikungunya virus, Zika virus, and Dengue virus. The diverse and rapidly changing landscape of possible causes of viral encephalitis poses great challenges for traditional candidate-based infectious disease diagnostics that already fail to identify a causative pathogen in approximately 50% of encephalitis cases. We present the case of a 14-year-old girl on immunosuppression for a renal transplant who presented with acute meningoencephalitis. Traditional diagnostics failed to identify an etiology. RNA extracted from her cerebrospinal fluid was subjected to unbiased metagenomic deep sequencing, enhanced with the use of a Cas9-based technique for host depletion. This analysis identified West Nile virus (WNV). Convalescent serum serologies subsequently confirmed WNV seroconversion. These results support a clear clinical role for metagenomic deep sequencing in the setting of suspected viral encephalitis, especially in the context of the high-risk transplant patient population. © 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

  2. An investigation of depression and fatigue post West Nile virus infection.

    PubMed

    Berg, Patti J; Smallfield, Stacy; Svien, Lana

    2010-04-01

    The purpose of this study was to examine depression and fatigue in individuals with a seropositive confirmed history of West Nile virus (WNV) infection. The South Dakota State Epidemiologist sent 218 letters inviting residents with a diagnosis of WNV to participate in the study. Forty-five subjects were tested. An occupational therapist and a physical therapist met with each participant to assess performance parameters, including depression and fatigue levels. Subjects (n=42) completed the Revised Center for Epidemiologic Studies Depression Scale (CES-D) during the assessment. The Modified Fatigue Impact Scale (MFIS) was sent to participants as a follow-up questionnaire, and 29 were returned. Subjects were placed within one of three diagnosis groups: West Nile Fever (WNF), West Nile Neuroinvasive Disease (WNND) and WNV without fever or neuroinvasive disease (clinical/unspecified). Frequency of those reporting low risk of depression was similar between diagnosis groups (each approximating 75 percent). Depression severity differences were noted, with subjects diagnosed with WNND more likely to report "severe" risk for depression. Low correlations between depression and overall fatigue, depression and cognitive fatigue, and depression and psychosocial fatigue indicators were found. There was little if any correlation between depression and physical fatigue indicators. Mean CES-D scores for subjects between 13 to 18 months post infection fell within the mild-moderate risk for depression category. Identifying depression risk is useful for patient referral purposes and may help minimize symptoms of depression correlated with fatigue, especially following hospitalization for WNV infection.

  3. West Nile virus and hemoparasites in captive snowy owls (Bubo scandiacus)--management strategies to optimize survival.

    PubMed

    Harasym, Carol A

    2008-11-01

    In August 2005, 2 members of a group of 6 captive snowy owls (Bubo scandiacus) in central Saskatchewan died of West Nile virus infection. One of these owls and 3 of the remaining owls had significant numbers of circulating hemoparasites. Management strategies are suggested to reduce morbidity and mortality.

  4. Serologic diagnosis of West Nile and St. Louis encephalitis virus infections in domestic chickens.

    PubMed

    Patiris, Peter J; Oceguera, Leopoldo F; Peck, George W; Chiles, Robert E; Reisen, William K; Hanson, Carl V

    2008-03-01

    Adult domestic chickens were infected with West Nile virus (WNV) or St. Louis encephalitis virus (SLEV) and challenged with homologous or heterologous virus at 21 or 56 days postinfection (dpi). Sera were collected at selected time points after infection and assayed by enzyme immunoassay (EIA), plaque reduction neutralization test (PRNT), and a Western blot (WB) alternative to PRNT. EIA results were sensitive and accurate (few false positives) but not specific, requiring a confirmatory test to determine virus infection history. PRNT results generally were specific until challenge, after which test results were frequently equivocal and inadequate to determine first or second infecting virus. WB results confirmed the serologic cross-reactivity between WNV and SLEV envelope protein. Non-structural protein 1 and pre-membrane protein reactivities were highly specific for WNV during SLEV infection, but less specific for SLEV during WNV infection. WB and PRNT specificities were similar for both viruses from 6 to 14 dpi, and sensitivities to WNV were virtually identical.

  5. Parameters of Mosquito-Enhanced West Nile Virus Infection.

    PubMed

    Moser, Lindsey A; Lim, Pei-Yin; Styer, Linda M; Kramer, Laura D; Bernard, Kristen A

    2016-01-01

    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. 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

  6. West nile poliomyelitis in a 7-year-old child.

    PubMed

    Hainline, Margaret L; Kincaid, John C; Carpenter, Denise L; Golomb, Meredith R

    2008-11-01

    West Nile poliomyelitis is a well-described neurologic manifestation of West Nile viral infection in adults. However, few reports have described this manifestation in children infected with West Nile virus. We describe a 7-year-old boy who developed West Nile poliomyelitis with flaccid paralysis of his left leg. Electrodiagnostic testing and radiologic imaging confirmed anterior horn cell injury. We report on his course clinically and electrodiagnostically over 20 months.

  7. Testing a West Nile virus vaccine in sandhill cranes (Grus canadensis)

    USGS Publications Warehouse

    Olsen, Glenn H.; Miller, K.; Docherty, D.; Sileo, L.; Chavez-Ramirez, Felipe

    2005-01-01

    Eight sandhill cranes (Grus canadensis) were vaccinated with a commercial equine West Nile virus vaccine (Fort Dodge Animal Health, Fort Dodge, Iowa, USA) at the USGS Patuxent Wildlife Research Center, Laurel, Maryland, USA. Three doses of the vaccine were given, the first dose (day 0) was followed by a second 21 days later and the third dose 7 days after the second day 28 after the first dose). All doses were 0.50 ml. In addition, 5 sandhill cranes were given injections of similar amounts of sterile water on the same schedule. Blood for complete blood counts, serum chemistries, and serological testing was collected at weekly intervals. Ten weeks after the first injection of the vaccine and 6 weeks after the last of the 3 injections of the vaccine, the cranes were shipped to the USGS National Wildlife Heath Center, Madison, Wisconsin, USA. After a two-week adjustment period, 11 of these cranes were injected intramuscularly with one mosquito dose of West Nile virus. Two of the vaccinated cranes were not challenged and acted as uninfected controls. One week post challenge the only abnormal findings were slight weight loss (average 6% loss since the time of challenge with West Nile virus) and elevated white blood cell counts (heterophilic leukocytosis). There were no deaths and no clinically ill cranes (unvaccinated or vaccinated cranes) among the 11 challenged birds. All cranes were euthanized 6 weeks post challenge, and necropsies were performed. Pre-challenge titers showed no titer response to the vaccinations. However, when challenged, vaccinated cranes developed titers more quickly (within 7-10 days), and were viremic and shed virus via the cloaca for a shorter period of time than the unvaccinated cranes (2-7 days for vaccinated cranes versus 2-10 days for unvaccinated cranes). No remarkable lesions were noted in any of the cranes during the necropsy examinations. Histopathological findings are available for only four of the cranes at this time. Three of those

  8. Detection of West Nile virus and tick-borne encephalitis virus in birds in Slovakia, using a universal primer set.

    PubMed

    Csank, Tomáš; Bhide, Katarína; Bencúrová, Elena; Dolinská, Saskia; Drzewnioková, Petra; Major, Peter; Korytár, Ľuboš; Bocková, Eva; Bhide, Mangesh; Pistl, Juraj

    2016-06-01

    West Nile virus (WNV) is a mosquito-borne neurotropic pathogen that presents a major public health concern. Information on WNV prevalence and circulation in Slovakia is insufficient. Oral and cloacal swabs and bird brain samples were tested for flavivirus RNA by RT-PCR using newly designed generic primers. The species designation was confirmed by sequencing. WNV was detected in swab and brain samples, whereas one brain sample was positive for tick-borne encephalitis virus (TBEV). The WNV sequences clustered with lineages 1 and 2. These results confirm the circulation of WNV in birds in Slovakia and emphasize the risk of infection of humans and horses.

  9. Persistence of Antibodies to West Nile Virus in Naturally Infected Rock Pigeons (Columba livia)

    PubMed Central

    Gibbs, Samantha E. J.; Hoffman, Douglas M.; Stark, Lillian M.; Marlenee, Nicole L.; Blitvich, Bradley J.; Beaty, Barry J.; Stallknecht, David E.

    2005-01-01

    Wild caught rock pigeons (Columba livia) with antibodies to West Nile virus were monitored for 15 months to determine antibody persistence and compare results of three serologic techniques. Antibodies persisted for the entire study as detected by epitope-blocking enzyme-linked immunosorbent assay and plaque reduction neutralization test. Maternal antibodies in squabs derived from seropositive birds persisted for an average of 27 days. PMID:15879030

  10. Evolutionary characterization of the West Nile Virus complete genome.

    PubMed

    Gray, R R; Veras, N M C; Santos, L A; Salemi, M

    2010-07-01

    The spatial dynamics of the West Nile Virus epidemic in North America are largely unknown. Previous studies that investigated the evolutionary history of the virus used sequence data from the structural genes (prM and E); however, these regions may lack phylogenetic information and obscure true evolutionary relationships. This study systematically evaluated the evolutionary patterns in the eleven genes of the WNV genome in order to determine which region(s) were most phylogenetically informative. We found that while the E region lacks resolution and can potentially result in misleading conclusions, the full NS3 or NS5 regions have strong phylogenetic signal. Furthermore, we show that geographic structure of WNV infection within the US is more pronounced than previously reported in studies that used the structural genes. We conclude that future evolutionary studies should focus on NS3 and NS5 in order to maximize the available sequences while retaining maximal interpretative power to infer temporal and geographic trends among WNV strains. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Spatiotemporal modeling of ecological and sociological predictors of West Nile virus in Suffolk County, NY, mosquitoes

    EPA Science Inventory

    Suffolk County, New York, is a locus for West Nile virus (WNV) infection in the American northeast that includes the majority of Long Island to the east of New York City. The county has a system of light and gravid traps used for mosquito collection and disease monitoring. In ord...

  12. Transmission of West Nile virus by Culex quinquefasciatus say infected with Culex Flavivirus Izabal.

    PubMed

    Kent, Rebekah J; Crabtree, Mary B; Miller, Barry R

    2010-05-04

    The natural history and potential impact of mosquito-specific flaviviruses on the transmission efficiency of West Nile virus (WNV) is unknown. The objective of this study was to determine whether or not prior infection with Culex flavivirus (CxFV) Izabal altered the vector competence of Cx. quinquefasciatus Say for transmission of a co-circulating strain of West Nile virus (WNV) from Guatemala. CxFV-negative Culex quinquefasciatus and those infected with CxFV Izabal by intrathoracic inoculation were administered WNV-infectious blood meals. Infection, dissemination, and transmission of WNV were measured by plaque titration on Vero cells of individual mosquito bodies, legs, or saliva, respectively, two weeks following WNV exposure. Additional groups of Cx. quinquefasciatus were intrathoracically inoculated with WNV alone or WNV+CxFV Izabal simultaneously, and saliva collected nine days post inoculation. Growth of WNV in Aedes albopictus C6/36 cells or Cx. quinquefasciatus was not inhibited by prior infection with CxFV Izabal. There was no significant difference in the vector competence of Cx. quinquefasciatus for WNV between mosquitoes uninfected or infected with CxFV Izabal across multiple WNV blood meal titers and two colonies of Cx. quinquefasciatus (p>0.05). However, significantly more Cx. quinquefasciatus from Honduras that were co-inoculated simultaneously with both viruses transmitted WNV than those inoculated with WNV alone (p = 0.0014). Co-inoculated mosquitoes that transmitted WNV also contained CxFV in their saliva, whereas mosquitoes inoculated with CxFV alone did not contain virus in their saliva. In the sequential infection experiments, prior infection with CxFV Izabal had no significant impact on WNV replication, infection, dissemination, or transmission by Cx. quinquefasciatus, however WNV transmission was enhanced in the Honduras colony when mosquitoes were inoculated simultaneously with both viruses.

  13. Declining growth rate of West Nile virus in North America.

    PubMed

    Snapinn, Katherine W; Holmes, Edward C; Young, David S; Bernard, Kristen A; Kramer, Laura D; Ebel, Gregory D

    2007-03-01

    To determine the demographic history of West Nile virus (WNV) in North America, we employed a coalescent method to envelope coding region data sets for the NY99 and WN02 genotypes. Although the observed genetic diversities in both genotypes were of approximately the same age, the mean rate of epidemiological growth of the WN02 population was approximately three times that of the NY99 population, a finding compatible with the recent dominance of the former genotype. However, there has also been a marked decrease in the recent growth rate of WN02, suggesting that WNV has reached its peak prevalence in North America.

  14. West Nile virus encephalomyelitis with polio-like paralysis & nigral degeneration.

    PubMed

    Schafernak, Kristian T; Bigio, Eileen H

    2006-11-01

    Patients infected with West Nile virus (WNV) may develop acute neurologic disease, which can be severe or even fatal, including WNV meningitis, encephalitis, and an irreversible acute flaccid paralysis or poliomyelitis-like syndrome. Movement disorders have also been described. We report combined neuronal loss, gliosis, and neurofibrillary tangle formation in the substantia nigra of a 41-year-old man with a history of WNV encephalomyelitis and poliomyelitis-like paralysis. Clinically our patient did not display parkinsonism, however, it is interesting to speculate whether, in the absence of the residual subacute poliomyelitis-like syndrome, the neuropathologic findings could have eventually evolved clinically into WNV-associated postencephalitic parkinsonism.

  15. West Nile Virus Infection of Birds, Mexico

    PubMed Central

    Guerrero-Sánchez, Sergio; Cuevas-Romero, Sandra; Nemeth, Nicole M.; Trujillo-Olivera, María Teresa Jesús; Worwa, Gabriella; Dupuis, Alan; Brault, Aaron C.; Kramer, Laura D.; Komar, Nicholas

    2011-01-01

    West Nile virus (WNV) has caused disease in humans, equids, and birds at lower frequency in Mexico than in the United States. We hypothesized that the seemingly reduced virulence in Mexico was caused by attenuation of the Tabasco strain from southeastern Mexico, resulting in lower viremia than that caused by the Tecate strain from the more northern location of Baja California. During 2006–2008, we tested this hypothesis in candidate avian amplifying hosts: domestic chickens, rock pigeons, house sparrows, great-tailed grackles, and clay-colored thrushes. Only great-tailed grackles and house sparrows were competent amplifying hosts for both strains, and deaths occurred in each species. Tecate strain viremia levels were higher for thrushes. Both strains produced low-level viremia in pigeons and chickens. Our results suggest that certain avian hosts within Mexico are competent for efficient amplification of both northern and southern WNV strains and that both strains likely contribute to bird deaths. PMID:22172633

  16. West Nile virus infection of birds, Mexico.

    PubMed

    Guerrero-Sánchez, Sergio; Cuevas-Romero, Sandra; Nemeth, Nicole M; Trujillo-Olivera, María Teresa Jesús; Worwa, Gabriella; Dupuis, Alan; Brault, Aaron C; Kramer, Laura D; Komar, Nicholas; Estrada-Franco, José Guillermo

    2011-12-01

    West Nile virus (WNV) has caused disease in humans, equids, and birds at lower frequency in Mexico than in the United States. We hypothesized that the seemingly reduced virulence in Mexico was caused by attenuation of the Tabasco strain from southeastern Mexico, resulting in lower viremia than that caused by the Tecate strain from the more northern location of Baja California. During 2006-2008, we tested this hypothesis in candidate avian amplifying hosts: domestic chickens, rock pigeons, house sparrows, great-tailed grackles, and clay-colored thrushes. Only great-tailed grackles and house sparrows were competent amplifying hosts for both strains, and deaths occurred in each species. Tecate strain viremia levels were higher for thrushes. Both strains produced low-level viremia in pigeons and chickens. Our results suggest that certain avian hosts within Mexico are competent for efficient amplification of both northern and southern WNV strains and that both strains likely contribute to bird deaths.

  17. Characterization of the functional requirements of West Nile virus membrane fusion.

    PubMed

    Moesker, Bastiaan; Rodenhuis-Zybert, Izabela A; Meijerhof, Tjarko; Wilschut, Jan; Smit, Jolanda M

    2010-02-01

    Flaviviruses infect their host cells by a membrane fusion reaction. In this study, we performed a functional analysis of the membrane fusion properties of West Nile virus (WNV) with liposomal target membranes. Membrane fusion was monitored continuously using a lipid mixing assay involving the fluorophore, pyrene. Fusion of WNV with liposomes occurred on the timescale of seconds and was strictly dependent on mildly acidic pH. Optimal fusion kinetics were observed at pH 6.3, the threshold for fusion being pH 6.9. Preincubation of the virus alone at pH 6.3 resulted in a rapid loss of fusion capacity. WNV fusion activity is strongly promoted by the presence of cholesterol in the target membrane. Furthermore, we provide direct evidence that cleavage of prM to M is a requirement for fusion activity of WNV.

  18. West Nile virus disease and other arboviral diseases--United States, 2010.

    PubMed

    2011-08-05

    Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. Since West Nile virus (WNV) was first detected in the Western Hemisphere in 1999, it has become the leading cause of neuroinvasive arboviral disease in the United States. However, several other arboviruses continue to cause sporadic cases and seasonal outbreaks of neuroinvasive disease (i.e., meningitis, encephalitis, or acute flaccid paralysis). This report summarizes surveillance data reported to CDC in 2010 for WNV and other nationally notifiable arboviruses (excluding dengue, which is reported separately). In 2010, 40 states and the District of Columbia (DC) reported 1,021 cases of WNV disease. Of these, 629 (62%) were classified as WNV neuroinvasive disease, for a national incidence of 0.20 per 100,000 population. States with the highest incidence were Arizona (1.60), New Mexico (1.03), Nebraska (0.55), and Colorado (0.51). After WNV, the next most commonly reported cause of neuroinvasive arboviral disease was California serogroup viruses (CALV), with 68 cases, followed by eastern equine encephalitis virus (EEEV), 10 cases, St. Louis encephalitis virus (SLEV), eight cases, and Powassan virus (POWV), eight cases. WNV and other arboviruses continue to cause focal outbreaks and severe illness in substantial numbers of persons in the United States. Maintaining surveillance remains important to guide arboviral disease prevention activities.

  19. Exposure to West Nile virus and tick-borne encephalitis virus in dogs in Spain.

    PubMed

    García-Bocanegra, I; Jurado-Tarifa, E; Cano-Terriza, D; Martínez, R; Pérez-Marín, J E; Lecollinet, S

    2018-06-01

    In the past decade, the spread of emerging zoonotic flaviviruses (genus Flavivirus, family Flaviviridae) has been reported in many regions worldwide, representing a threat to both human and animal health. A serosurvey was carried out to assess exposure and risk factors associated with antigenically related flaviviruses, particularly West Nile virus (WNV), Usutu virus (USUV) and tick-borne encephalitis virus (TBEV), in dogs in Spain. Flavivirus antibodies were detected in 39 of 815 dogs (4.8%; 95% CI: 3.3-6.3) by bELISA. Significantly higher seropositivity was observed in hunting dogs compared to pet dogs. Virus neutralization tests confirmed WNV-specific and TBEV-specific antibodies in 11 and 14 bELISA-positive dogs, respectively. This is the first serosurvey of WNV and TBEV in dogs in Spain and the first report of TBEV circulation in this country. The seropositivity obtained indicates widespread, but not homogeneous, distribution of WNV and TBEV in dogs in Spain. In 2013 and 2015, WNV-seropositive dogs were detected in those areas of Andalusia where the highest number of WNV outbreaks were reported in both horses and humans. Antibodies against TBEV have been found in dogs sampled in two different periods and regions in Spain. Serosurveillance in dogs could be a complementary way of monitoring the activity of emerging flaviviruses in Spain. © 2018 Blackwell Verlag GmbH.

  20. Characterization of virulent West Nile virus Kunjin strain, Australia, 2011.

    PubMed

    Frost, Melinda J; Zhang, Jing; Edmonds, Judith H; Prow, Natalie A; Gu, Xingnian; Davis, Rodney; Hornitzky, Christine; Arzey, Kathleen E; Finlaison, Deborah; Hick, Paul; Read, Andrew; Hobson-Peters, Jody; May, Fiona J; Doggett, Stephen L; Haniotis, John; Russell, Richard C; Hall, Roy A; Khromykh, Alexander A; Kirkland, Peter D

    2012-05-01

    To determine the cause of an unprecedented outbreak of encephalitis among horses in New South Wales, Australia, in 2011, we performed genomic sequencing of viruses isolated from affected horses and mosquitoes. Results showed that most of the cases were caused by a variant West Nile virus (WNV) strain, WNV(NSW2011), that is most closely related to WNV Kunjin (WNV(KUN)), the indigenous WNV strain in Australia. Studies in mouse models for WNV pathogenesis showed that WNV(NSW2011) is substantially more neuroinvasive than the prototype WNV(KUN) strain. In WNV(NSW2011), this apparent increase in virulence over that of the prototype strain correlated with at least 2 known markers of WNV virulence that are not found in WNV(KUN). Additional studies are needed to determine the relationship of the WNV(NSW2011) strain to currently and previously circulating WNV(KUN) strains and to confirm the cause of the increased virulence of this emerging WNV strain.

  1. Virulence and Evolution of West Nile Virus, Australia, 1960-2012.

    PubMed

    Prow, Natalie A; Edmonds, Judith H; Williams, David T; Setoh, Yin X; Bielefeldt-Ohmann, Helle; Suen, Willy W; Hobson-Peters, Jody; van den Hurk, Andrew F; Pyke, Alyssa T; Hall-Mendelin, Sonja; Northill, Judith A; Johansen, Cheryl A; Warrilow, David; Wang, Jianning; Kirkland, Peter D; Doggett, Stephen; Andrade, Christy C; Brault, Aaron C; Khromykh, Alexander A; Hall, Roy A

    2016-08-01

    Worldwide, West Nile virus (WNV) causes encephalitis in humans, horses, and birds. The Kunjin strain of WNV (WNVKUN) is endemic to northern Australia, but infections are usually asymptomatic. In 2011, an unprecedented outbreak of equine encephalitis occurred in southeastern Australia; most of the ≈900 reported cases were attributed to a newly emerged WNVKUN strain. To investigate the origins of this virus, we performed genetic analysis and in vitro and in vivo studies of 13 WNVKUN isolates collected from different regions of Australia during 1960-2012. Although no disease was recorded for 1984, 2000, or 2012, isolates collected during those years (from Victoria, Queensland, and New South Wales, respectively) exhibited levels of virulence in mice similar to that of the 2011 outbreak strain. Thus, virulent strains of WNVKUN have circulated in Australia for >30 years, and the first extensive outbreak of equine disease in Australia probably resulted from a combination of specific ecologic and epidemiologic conditions.

  2. Genotype-specific variation in West Nile virus dispersal in California.

    PubMed

    Duggal, Nisha K; Reisen, William K; Fang, Ying; Newman, Ruchi M; Yang, Xiao; Ebel, Gregory D; Brault, Aaron C

    2015-11-01

    West Nile virus (WNV) is an arbovirus that was first reported in North America in New York in 1999 and, by 2003, had spread more than 4000 km to California. However, variation in viral genetics associated with spread is not well understood. Herein, we report sequences for more than 100 WNV isolates made from mosquito pools that were collected from 2003 to 2011 as part of routine surveillance by the California Mosquito-borne Virus Surveillance System. We performed phylogeographic analyses and demonstrated that 5 independent introductions of WNV (1 WN02 genotype strain and 4 SW03 genotype strains) occurred in California. The SW03 genotype of WNV was constrained to the southwestern U.S. and had a more rapid rate of spread. In addition, geographic constraint of WNV strains within a single region for up to 6 years suggest viral maintenance has been driven by resident, rather than migratory, birds and overwintering in mosquitoes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Further circulation of West Nile and Usutu viruses in wild birds in Italy.

    PubMed

    Llopis, Isis Victoriano; Rossi, Luca; Di Gennaro, Annapia; Mosca, Andrea; Teodori, Liana; Tomassone, Laura; Grego, Elena; Monaco, Federica; Lorusso, Alessio; Savini, Giovanni

    2015-06-01

    Usutu virus (USUV) and West Nile virus (WNV) are emerging pathogens that can cause neurological disease in humans. From March 2012 to June 2013, a sero-survey on wild birds was carried out to investigate the circulation of both viruses in Northwest (NW) Italy. Samples belonging to 47 different bird species have been collected using a volunteer based network and a wildlife rehabilitation center. Four of 297 serum samples had neutralizing antibodies against USUV (P=1.34%, IC 95% 0.36-3.4), while 10 of 233 samples tested positive for WNV (P=4.29%, IC 95% 2.07-7.75). Neutralizing antibodies for WNV were significantly more prevalent (p<0.001) in trans-Saharan migrants (P=21%, IC 95% 9.55-37.3) than in resident and short-distance birds, but no migratory habit-related differences were found for USUV. Antibodies in resident bird species suggest that both viruses are circulating in NW Italy. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Large Human Outbreak of West Nile Virus Infection in North-Eastern Italy in 2012

    PubMed Central

    Barzon, Luisa; Pacenti, Monia; Franchin, Elisa; Pagni, Silvana; Lavezzo, Enrico; Squarzon, Laura; Martello, Thomas; Russo, Francesca; Nicoletti, Loredana; Rezza, Giovanni; Castilletti, Concetta; Capobianchi, Maria Rosaria; Salcuni, Pasquale; Cattai, Margherita; Cusinato, Riccardo; Palù, Giorgio

    2013-01-01

    Human cases of West Nile virus (WNV) disease have been reported in Italy since 2008. So far, most cases have been identified in north-eastern Italy, where, in 2012, the largest outbreak of WNV infection ever recorded in Italy occurred. Most cases of the 2012 outbreak were identified in the Veneto region, where a special surveillance plan for West Nile fever was in place. In this outbreak, 25 cases of West Nile neuroinvasive disease and 17 cases of fever were confirmed. In addition, 14 WNV RNA-positive blood donors were identified by screening of blood and organ donations and two cases of asymptomatic infection were diagnosed by active surveillance of subjects at risk of WNV exposure. Two cases of death due to WNND were reported. Molecular testing demonstrated the presence of WNV lineage 1 in all WNV RNA-positive patients and, in 15 cases, infection by the novel Livenza strain was ascertained. Surveillance in other Italian regions notified one case of neuroinvasive disease in the south of Italy and two cases in Sardinia. Integrated surveillance for WNV infection remains a public health priority in Italy and vector control activities have been strengthened in areas of WNV circulation. PMID:24284876

  5. Assessing human risk of illness with West Nile virus mosquito surveillance data to improve public health preparedness

    USDA-ARS?s Scientific Manuscript database

    Surveillance for West Nile virus (WNV) and other mosquito-borne pathogens involves costly and time-consuming collection and testing of mosquito samples. One difficulty faced by public health personnel is how to interpret mosquito data relative to human risk, thus leading to a failure to fully exploi...

  6. Serosurvey for West Nile virus antibodies in Steller's Jays (Cyanocitta stelleri) captured in coastal California

    USGS Publications Warehouse

    West, Elena; Hofmeister, Erik K.; Peery, M. Zach

    2017-01-01

    West Nile virus (WNV) was first detected in New York in 1999 and, during its expansion across the continental US, southern Canada, and Mexico, members of the Corvidae (ravens, crows, magpies, and jays) were frequently infected and highly susceptible to the virus. As part of a behavioral study of Steller's Jays (Cyanocitta stelleri) conducted from 2011–2014 in the coastal California counties of San Mateo and Santa Cruz, 380 Steller's Jays were captured and tested for antibodies to WNV. Using the wild bird IgG enzyme linked immunoassay, we failed to detect antibodies to WNV, indicating either that there was no previous exposure to the virus or that exposed birds had died.

  7. Recovery of West Nile Virus Envelope Protein Domain III Chimeras with Altered Antigenicity and Mouse Virulence

    PubMed Central

    McAuley, Alexander J.; Torres, Maricela; Plante, Jessica A.; Huang, Claire Y.-H.; Bente, Dennis A.

    2016-01-01

    ABSTRACT Flaviviruses are positive-sense, single-stranded RNA viruses responsible for millions of human infections annually. The envelope (E) protein of flaviviruses comprises three structural domains, of which domain III (EIII) represents a discrete subunit. The EIII gene sequence typically encodes epitopes recognized by virus-specific, potently neutralizing antibodies, and EIII is believed to play a major role in receptor binding. In order to assess potential interactions between EIII and the remainder of the E protein and to assess the effects of EIII sequence substitutions on the antigenicity, growth, and virulence of a representative flavivirus, chimeric viruses were generated using the West Nile virus (WNV) infectious clone, into which EIIIs from nine flaviviruses with various levels of genetic diversity from WNV were substituted. Of the constructs tested, chimeras containing EIIIs from Koutango virus (KOUV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV), and Bagaza virus (BAGV) were successfully recovered. Characterization of the chimeras in vitro and in vivo revealed differences in growth and virulence between the viruses, with in vivo pathogenesis often not being correlated with in vitro growth. Taken together, the data demonstrate that substitutions of EIII can allow the generation of viable chimeric viruses with significantly altered antigenicity and virulence. IMPORTANCE The envelope (E) glycoprotein is the major protein present on the surface of flavivirus virions and is responsible for mediating virus binding and entry into target cells. Several viable West Nile virus (WNV) variants with chimeric E proteins in which the putative receptor-binding domain (EIII) sequences of other mosquito-borne flaviviruses were substituted in place of the WNV EIII were recovered, although the substitution of several more divergent EIII sequences was not tolerated. The differences in virulence and tissue tropism observed with the chimeric

  8. Recovery of West Nile Virus Envelope Protein Domain III Chimeras with Altered Antigenicity and Mouse Virulence.

    PubMed

    McAuley, Alexander J; Torres, Maricela; Plante, Jessica A; Huang, Claire Y-H; Bente, Dennis A; Beasley, David W C

    2016-05-01

    Flaviviruses are positive-sense, single-stranded RNA viruses responsible for millions of human infections annually. The envelope (E) protein of flaviviruses comprises three structural domains, of which domain III (EIII) represents a discrete subunit. The EIII gene sequence typically encodes epitopes recognized by virus-specific, potently neutralizing antibodies, and EIII is believed to play a major role in receptor binding. In order to assess potential interactions between EIII and the remainder of the E protein and to assess the effects of EIII sequence substitutions on the antigenicity, growth, and virulence of a representative flavivirus, chimeric viruses were generated using the West Nile virus (WNV) infectious clone, into which EIIIs from nine flaviviruses with various levels of genetic diversity from WNV were substituted. Of the constructs tested, chimeras containing EIIIs from Koutango virus (KOUV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV), and Bagaza virus (BAGV) were successfully recovered. Characterization of the chimeras in vitro and in vivo revealed differences in growth and virulence between the viruses, within vivo pathogenesis often not being correlated within vitro growth. Taken together, the data demonstrate that substitutions of EIII can allow the generation of viable chimeric viruses with significantly altered antigenicity and virulence. The envelope (E) glycoprotein is the major protein present on the surface of flavivirus virions and is responsible for mediating virus binding and entry into target cells. Several viable West Nile virus (WNV) variants with chimeric E proteins in which the putative receptor-binding domain (EIII) sequences of other mosquito-borne flaviviruses were substituted in place of the WNV EIII were recovered, although the substitution of several more divergent EIII sequences was not tolerated. The differences in virulence and tissue tropism observed with the chimeric viruses indicate a

  9. Biological and phylogenetic characteristics of West African lineages of West Nile virus.

    PubMed

    Fall, Gamou; Di Paola, Nicholas; Faye, Martin; Dia, Moussa; Freire, Caio César de Melo; Loucoubar, Cheikh; Zanotto, Paolo Marinho de Andrade; Faye, Ousmane; Sall, Amadou Alpha

    2017-11-01

    The West Nile virus (WNV), isolated in 1937, is an arbovirus (arthropod-borne virus) that infects thousands of people each year. Despite its burden on global health, little is known about the virus' biological and evolutionary dynamics. As several lineages are endemic in West Africa, we obtained the complete polyprotein sequence from three isolates from the early 1990s, each representing a different lineage. We then investigated differences in growth behavior and pathogenicity for four distinct West African lineages in arthropod (Ap61) and primate (Vero) cell lines, and in mice. We found that genetic differences, as well as viral-host interactions, could play a role in the biological properties in different WNV isolates in vitro, such as: (i) genome replication, (ii) protein translation, (iii) particle release, and (iv) virulence. Our findings demonstrate the endemic diversity of West African WNV strains and support future investigations into (i) the nature of WNV emergence, (ii) neurological tropism, and (iii) host adaptation.

  10. The nucleolar helicase DDX56 redistributes to West Nile virus assembly sites.

    PubMed

    Reid, Colleen R; Hobman, Tom C

    2017-01-01

    Flaviviruses, including the human pathogen, West Nile virus (WNV), are known to co-opt many host factors for their replication and propagation. To this end, we previously reported that the nucleolar DEAD-box RNA helicase, DDX56, is important for production of infectious WNV virions. In this study, we show that WNV infection results in relocalization of DDX56 from nucleoli to virus assembly sites on the endoplasmic reticululm (ER), an observation that is consistent with a role for DDX56 in WNV virion assembly. Super-resolution microscopy revealed that capsid and DDX56 localized to the same subcompartment of the ER, however, unexpectedly, stable interaction between these two proteins was only detected in the nucleus. Together, these data suggest that DDX56 relocalizes to the site of virus assembly during WNV infection and that its interaction with WNV capsid in the cytoplasm may occur transiently during virion morphogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Integrated analysis of human-animal-vector surveillance: West Nile virus infections in Austria, 2015-2016.

    PubMed

    Kolodziejek, Jolanta; Jungbauer, Christof; Aberle, Stephan W; Allerberger, Franz; Bagó, Zoltán; Camp, Jeremy V; Dimmel, Katharina; de Heus, Phebe; Kolodziejek, Michael; Schiefer, Peter; Seidel, Bernhard; Stiasny, Karin; Nowotny, Norbert

    2018-03-14

    The results of integrated human and veterinary surveillance for West Nile virus (WNV) infections in Austria during the transmission seasons 2015 and 2016 are shown. Altogether WNV nucleic acid was detected in 21 humans, horses, wild birds and mosquito pools. In detail: in four human clinical cases [two cases of West Nile fever (WNF) and two cases of West Nile neuroinvasive disease (WNND)]; eight blood donors [among 145,541 tested donations], of which three remained asymptomatic and five subsequently developed mild WNF; two horses with WNND, of which one recovered and one had to be euthanized; two wild birds [one goshawk and one falcon, both succumbed to WNND]; and five Culex pipiens mosquito pools. Compared to previous years the number of infections increased remarkably. All infections were recorded in the city of Vienna and neighboring regions of Lower Austria. Sixteen coding-complete WNV sequences were established which were closely related to each other and to other Austrian, Czech and Italian viruses, all belonging to the Central/Southern European cluster of WNV sublineage 2d. However, several genetically slightly different WNV strains seem to co-circulate in the same area, as demonstrated by phylogenetic analysis. Based on detailed sequence analysis, all newly discovered Austrian WNV strains had the potential to cause neurological disease, but no correlation was found between severity of disease and the analyzed genetic virulence/neuroinvasiveness markers. Results of integrated human-animal-vector surveillance presented in this paper provide a comprehensive description of WNV activity in the region and will facilitate proactive public health measures to prevent or mitigate potential outbreaks.

  12. A spatiotemporal model of ecological and sociological predictors of West Nile virus in Suffolk County, NY mosquitoes

    EPA Science Inventory

    Background/Question/Methods Suffolk County, New York is a locus for West Nile virus (WNV) infection in the American northeast that includes the majority of Long Island to the east of New York City. The county has a robust system of light and gravid traps used for mosquito collect...

  13. A Fatal Neuroinvasive West Nile Virus Infection in a Traveler Returning from Madagascar: Clinical, Epidemiological and Veterinary Investigations

    PubMed Central

    Larrieu, Sophie; Cardinale, Eric; Ocquidant, Philippe; Roger, Matthieu; Lepec, Richard; Delatte, Hélène; Camuset, Guillaume; Desprès, Philippe; Brottet, Elise; Charlin, Cyril; Michault, Alain

    2013-01-01

    A 58-year-old woman living in Reunion Island and returning from Madagascar was hospitalized for neuroinvasive encephalitis and died 1 month later. West Nile virus (WNV) infection was biologically confirmed by detection of immunoglobulin M (IgM) reactive with WNV antigens in both cerebrospinal fluid and serum, and weak neutralizing activity was also detected. A veterinary survey performed in her traveling area showed a seroprevalence of WNV of 28.7% (95% confidence interval [CI] = 21.1–36.3) in adult poultry, confirming an active circulation of the virus. Development of a severe form could be related to a weak antibody response, because the patient presented low IgM and IgG titers. This case report underlines the constant risk of emergence of West Nile in Indian Ocean territories, including Reunion Island where competent vectors are widely present during the whole year. PMID:23751400

  14. Short report: Changes in West Nile virus seroprevalence and antibody titers among Wisconsin mesopredators 2003-2006

    USGS Publications Warehouse

    Docherty, D.E.; Samuel, M.D.; Egstad, K.F.; Griffin, K.M.; Nolden, C.A.; Karwal, L.; Ip, Hon S.

    2009-01-01

    After the 2001 occurrence of West Nile virus (WNV) in Wisconsin (WI), we collected sera, during 2003-2006, from south-central WI mesopredators. We tested these sera to determine WNV antibody prevalence and geometric mean antibody titer (GMAT). Four-fold higher antibody prevalence and 2-fold higher GMAT in 2003-2004 indicated greater exposure of mesopredators to WNV during the apparent epizootic phase. The period 2005-2006 was likely the enzootic phase because WNV antibody prevalence fell to a level similar to other flaviviruses. Our results suggest that, in mesopredators, vector-borne transmission is the primary route of infection and WNV antibodies persist for < 1 year. Mesopredators may be sensitive indicators of West Nile virus spill-over into humans and horses. Mesopredator sero-surveys may complement dead crow surveillance by providing additional data for the timing of public health interventions. Research is needed to clarify the dynamics of WNV infection in these mammals and their role as potential WNV amplifiers. Copyright ?? 2009 by The American Society of Tropical Medicine and Hygiene.

  15. Human West Nile Virus Disease Outbreak in Pakistan, 2015-2016.

    PubMed

    Khan, Erum; Barr, Kelli L; Farooqi, Joveria Qais; Prakoso, Dhani; Abbas, Alizae; Khan, Zain Y; Ashi, Shanze; Imtiaz, Kehkashan; Aziz, Z; Malik, Faisal; Lednicky, John A; Long, Maureen T

    2018-01-01

    Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological disease in human patients in this country. Of 997 enrolled patients presenting with clinical features suggestive of arboviral disease, 105 were positive for WNV IgM antibodies, and 71 of these patients possessed WNV-specific neutralizing antibodies. Cross-reactivity of WNV IgM antibodies with Japanese encephalitis virus (JEV) occurred in 75 of these 105 patients. WNV co-infections with Dengue viruses were not a contributing factor for the severity of disease. Nor did prior exposure to dengue virus contribute to incidence of neurological involvement in WNV-infected patients. Patients with WNV infections were more likely to present with altered mental status, seizures, and reduced Glasgow Coma scores when compared with JEV-infected patients. Human WNV cases and vector numbers exhibited a temporal correlation with climate.

  16. Concurrent occurrence of human and equine West Nile virus infections in Central Anatolia, Turkey: the first evidence for circulation of lineage 1 viruses.

    PubMed

    Ozkul, Aykut; Ergunay, Koray; Koysuren, Aydan; Alkan, Feray; Arsava, Ethem M; Tezcan, Seda; Emekdas, Gurol; Hacioglu, Sabri; Turan, Mahur; Us, Durdal

    2013-07-01

    West Nile fever is an important zoonotic infection caused by West Nile virus (WNV), a member of the Flaviviridae. Previous serological data from Turkey suggest widespread WNV circulation. This report includes cases of human and equine WNV infections occurring concurrently, and manifesting as central nervous system infections, in two neighboring provinces of Central Anatolia, Turkey. A partial phylogenetic analysis of the causative virus is given for the first time. The cases were reported in February (horses) and March (human). Symptoms of the disease were similar in the two species, characterized by neurological manifestations suggesting meningoencephalitis. Real-time/nested PCRs and commercial immunoassays and a plaque reduction neutralization assay were employed for the detection of viral RNA and specific antibodies, respectively. WNV RNAs were detected in buffy coat (horses) and cerebrospinal fluid (human) samples. Partial nucleotide sequences of the E-gene coding region revealed that the strains are closely related to viruses of lineage 1, clade 1a. Accompanying equine serosurveillance demonstrated WNV-specific antibodies in 31.6% of the samples. This is the first report of acute WNV infections caused by lineage 1 strains from Turkey, in concordance with previous reports from some European and North African countries. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. Differential Virulence and Pathogenesis of West Nile Viruses

    PubMed Central

    Donadieu, Emilie; Bahuon, Céline; Lowenski, Steeve; Zientara, Stéphan; Coulpier, Muriel; Lecollinet, Sylvie

    2013-01-01

    West Nile virus (WNV) is a neurotropic flavivirus that cycles between mosquitoes and birds but that can also infect humans, horses, and other vertebrate animals. In most humans, WNV infection remains subclinical. However, 20%–40% of those infected may develop WNV disease, with symptoms ranging from fever to meningoencephalitis. A large variety of WNV strains have been described worldwide. Based on their genetic differences, they have been classified into eight lineages; the pathogenic strains belong to lineages 1 and 2. Ten years ago, Beasley et al. (2002) found that dramatic differences exist in the virulence and neuroinvasion properties of lineage 1 and lineage 2 WNV strains. Further insights on how WNV interacts with its hosts have recently been gained; the virus acts either at the periphery or on the central nervous system (CNS), and these observed differences could help explain the differential virulence and neurovirulence of WNV strains. This review aims to summarize the current state of knowledge on factors that trigger WNV dissemination and CNS invasion as well as on the inflammatory response and CNS damage induced by WNV. Moreover, we will discuss how WNV strains differentially interact with the innate immune system and CNS cells, thus influencing WNV pathogenesis. PMID:24284878

  18. Differential virulence and pathogenesis of West Nile viruses.

    PubMed

    Donadieu, Emilie; Bahuon, Céline; Lowenski, Steeve; Zientara, Stéphan; Coulpier, Muriel; Lecollinet, Sylvie

    2013-11-22

    West Nile virus (WNV) is a neurotropic flavivirus that cycles between mosquitoes and birds but that can also infect humans, horses, and other vertebrate animals. In most humans, WNV infection remains subclinical. However, 20%-40% of those infected may develop WNV disease, with symptoms ranging from fever to meningoencephalitis. A large variety of WNV strains have been described worldwide. Based on their genetic differences, they have been classified into eight lineages; the pathogenic strains belong to lineages 1 and 2. Ten years ago, Beasley et al. (2002) found that dramatic differences exist in the virulence and neuroinvasion properties of lineage 1 and lineage 2 WNV strains. Further insights on how WNV interacts with its hosts have recently been gained; the virus acts either at the periphery or on the central nervous system (CNS), and these observed differences could help explain the differential virulence and neurovirulence of WNV strains. This review aims to summarize the current state of knowledge on factors that trigger WNV dissemination and CNS invasion as well as on the inflammatory response and CNS damage induced by WNV. Moreover, we will discuss how WNV strains differentially interact with the innate immune system and CNS cells, thus influencing WNV pathogenesis.

  19. West Nile virus reemergence in Romania: a serologic survey in host species.

    PubMed

    Ludu Oslobanu, Elena Luanda; Mihu-Pintilie, Alin; Anită, Dragos; Anita, Adriana; Lecollinet, Sylvie; Savuta, Gheorghe

    2014-05-01

    The presence of West Nile virus (WNV) in humans has been known in Romania since the 1950s; the 1996 epidemics emphasized the reemergence potential of WNV in Romania. Serological surveys made on susceptible species, known as good sentinels or reservoir hosts, e.g., horses, wild and domestic birds were undertaken from 2006-2011. Our results corroborated incidence data in human patients and other recent seroprevalence studies in animals, and should partially clarify the emergence of WNV in the eastern rural territories of Romania. It also highlighted risk zones for endemic WNV infection in Romania.

  20. Close Relationship between West Nile Virus from Turkey and Lineage 1 Strain from Central African Republic

    PubMed Central

    Ergunay, Koray; Bakonyi, Tamas; Nowotny, Norbert

    2015-01-01

    We sequenced West Nile viruses (WNVs) from Turkey and found close relationships to WNV lineage 1 strain ArB310/67 from the Central African Republic, distinct from other WNVs circulating in the Mediterranean Basin, eastern Europe, and the Middle East. These findings suggest independent introductions of WNV strains from Africa to the Middle East. PMID:25625703

  1. West Nile virus and hemoparasites in captive snowy owls (Bubo scandiacus) — management strategies to optimize survival

    PubMed Central

    Harasym, Carol A.

    2008-01-01

    In August 2005, 2 members of a group of 6 captive snowy owls (Bubo scandiacus) in central Saskatchewan died of West Nile virus infection. One of these owls and 3 of the remaining owls had significant numbers of circulating hemoparasites. Management strategies are suggested to reduce morbidity and mortality. PMID:19183740

  2. West Nile Virus encephalitis in intensive care: a small mosquito, a tremendous danger.

    PubMed

    Capuzzo, M; Cadorin, D; Perna, P; Vitali, S; Libanore, M; Cavazzini, L; Alvisi, R

    2011-12-01

    The authors describe two of three cases of West Nile virus (WNV) meningoencephalitis admitted to ICU in Ferrara (south of Po River) underlying the main common features. They focus on the difficulties in diagnosis, with key-points including seasonality (late summer in Italy), unspecific flu-like symptoms at the beginning, as hyperpyrexia, myalgia and asthenia, followed by neurological impairment, and use of steroids in the patient clinical history. Special attention is deserved to the poor outcome at both short and long term.

  3. Innate Immune Control of West Nile Virus Infection

    PubMed Central

    Arjona, Alvaro; Wang, Penghua; Montgomery, Ruth R.; Fikrig, Erol

    2011-01-01

    West Nile virus (WNV), from the Flaviviridae family, is a re-emerging zoonotic pathogen of medical importance. In humans, WNV infection may cause life-threatening meningoencephalitis or long-term neurologic sequelae. WNV is transmitted by Culex spp mosquitoes and both the arthropod vector and the mammalian host are equipped with antiviral innate immune mechanisms sharing a common phylogeny. As far as the current evidence is able to demonstrate, mosquitoes primarily rely on RNA interference, Toll, Imd and JAK-STAT signaling pathways for limiting viral infection, while mammals are provided with these and other more complex antiviral mechanisms involving antiviral effectors, inflammatory mediators, and cellular responses triggered by highly specialized pathogen detection mechanisms that often resemble their invertebrate ancestry. This mini-review summarizes our current understanding of how the innate immune systems of the vector and the mammalian host react to WNV infection and shape its pathogenesis. PMID:21790942

  4. West Nile virus infection in horses, Indian ocean.

    PubMed

    Cardinale, E; Bernard, C; Lecollinet, S; Rakotoharinome, V M; Ravaomanana, J; Roger, M; Olive, M M; Meenowa, D; Jaumally, M R; Melanie, J; Héraud, J M; Zientara, S; Cêtre-Sossah, C

    2017-08-01

    The circulation of West Nile virus (WNV) in horses was investigated in the Southwest Indian ocean. In 2010, blood samples were collected from a total of 303 horses originating from Madagascar, Mauritius, Reunion and the Seychelles and tested for WNV-specific antibodies. An overall seroprevalence of 27.39% was detected in the Indian Ocean with the highest WNV antibody prevalence of 46.22% (95% CI: [37.4-55.2%]) in Madagascar. The age and origin of the horses were found to be associated with the WNV infection risk. This paper presents the first seroprevalence study investigating WN fever in horses in the Southwest Indian Ocean area and indicates a potential risk of infection for humans and animals. In order to gain a better understanding of WN transmission cycles, WNV surveillance needs to be implemented in each of the countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Experimental Infections of Wild Birds with West Nile Virus

    PubMed Central

    Pérez-Ramírez, Elisa; Llorente, Francisco; Jiménez-Clavero, Miguel Ángel

    2014-01-01

    Avian models of West Nile virus (WNV) disease have become pivotal in the study of infection pathogenesis and transmission, despite the intrinsic constraints that represents this type of experimental research that needs to be conducted in biosecurity level 3 (BSL3) facilities. This review summarizes the main achievements of WNV experimental research carried out in wild birds, highlighting advantages and limitations of this model. Viral and host factors that determine the infection outcome are analyzed in detail, as well as recent discoveries about avian immunity, viral transmission, and persistence achieved through experimental research. Studies of laboratory infections in the natural host will help to understand variations in susceptibility and reservoir competence among bird species, as well as in the epidemiological patterns found in different affected areas. PMID:24531334

  6. Climate Change and West Nile Virus in a Highly Endemic Region of North America

    PubMed Central

    Chen, Chen C.; Jenkins, Emily; Epp, Tasha; Waldner, Cheryl; Curry, Philip S.; Soos, Catherine

    2013-01-01

    The Canadian prairie provinces of Manitoba, Saskatchewan, and Alberta have reported the highest human incidence of clinical cases of West Nile virus (WNV) infection in Canada. The primary vector for WVN in this region is the mosquito Culex tarsalis. This study used constructed models and biological thresholds to predict the spatial and temporal distribution of Cx. tarsalis and WNV infection rate in the prairie provinces under a range of potential future climate and habitat conditions. We selected one median and two extreme outcome scenarios to represent future climate conditions in the 2020 (2010–2039), 2050 (2040–2069) and 2080 (2070–2099) time slices. In currently endemic regions, the projected WNV infection rate under the median outcome scenario in 2050 raised 17.91 times (ranged from 1.29-27.45 times for all scenarios and time slices) comparing to current climate conditions. Seasonal availability of Cx. tarsalis infected with WNV extended from June to August to include May and September. Moreover, our models predicted northward range expansion for Cx. tarsalis (1.06–2.56 times the current geographic area) and WNV (1.08–2.34 times the current geographic area). These findings predict future public and animal health risk of WNV in the Canadian prairie provinces. PMID:23880729

  7. Spatial Analysis of West Nile Virus: Predictive Risk Modeling of a Vector-borne Infectious Disease in Illinois by Means of NASA Earth Observation Systems

    NASA Technical Reports Server (NTRS)

    Renneboog, Nathan; Gathings, David; Hemmings, Sarah; Makasa, Emmanuel; Omer, Wigdan; Tipre, Meghan; Wright, Catherine; McAllister, Marilyn; Luvall, Jeffrey C.

    2009-01-01

    West Nile Virus is a mosquito-borne virus of the family Flaviviridae. It infects birds and various mammals, including humans, and can cause encephalitis that may prove fatal, notably among vulnerable populations. Since its identification in New York City in 1999, WNV has become established in a broad range of ecological settings throughout North America, infecting more than 25,300 people and killing 1133 as of 2008 (CDC,2009). WNV is transmitted by mosquitoes that feed on infected birds. As a result, the degree of human infection depends on local ecology and human exposure. This study hypothesizes that remote sensing and GIS can be used to analyze environmental determinants of WNV transmission, such as climate, elevation, land cover, and vegetation densities, to map areas of WNV risk for surveillance and intervention.

  8. Replication Cycle and Molecular Biology of the West Nile Virus

    PubMed Central

    Brinton, Margo A.

    2013-01-01

    West Nile virus (WNV) is a member of the genus Flavivirus in the family Flaviviridae. Flaviviruses replicate in the cytoplasm of infected cells and modify the host cell environment. Although much has been learned about virion structure and virion-endosomal membrane fusion, the cell receptor(s) used have not been definitively identified and little is known about the early stages of the virus replication cycle. Members of the genus Flavivirus differ from members of the two other genera of the family by the lack of a genomic internal ribosomal entry sequence and the creation of invaginations in the ER membrane rather than double-membrane vesicles that are used as the sites of exponential genome synthesis. The WNV genome 3' and 5' sequences that form the long distance RNA-RNA interaction required for minus strand initiation have been identified and contact sites on the 5' RNA stem loop for NS5 have been mapped. Structures obtained for many of the viral proteins have provided information relevant to their functions. Viral nonstructural protein interactions are complex and some may occur only in infected cells. Although interactions between many cellular proteins and virus components have been identified, the functions of most of these interactions have not been delineated. PMID:24378320

  9. Serosurvey for West Nile Virus Antibodies in Steller's Jays ( Cyanocitta stelleri ) Captured in Coastal California, USA.

    PubMed

    West, Elena; Hofmeister, Erik; Peery, M Zach

    2017-07-01

    West Nile virus (WNV) was first detected in New York in 1999 and, during its expansion across the continental US, southern Canada, and Mexico, members of the Corvidae (ravens, crows, magpies, and jays) were frequently infected and highly susceptible to the virus. As part of a behavioral study of Steller's Jays ( Cyanocitta stelleri ) conducted from 2011-14 in the coastal California counties of San Mateo and Santa Cruz, 380 Steller's Jays were captured and tested for antibodies to WNV. Using the wild bird immunoglobulin G enzyme linked immunoassay, we failed to detect antibodies to WNV, indicating either that there was no previous exposure to the virus or that exposed birds had died.

  10. West Nile virus infection in cats: ABCD guidelines on prevention and management.

    PubMed

    Egberink, Herman; Addie, Diane D; Boucraut-Baralon, Corine; Frymus, Tadeusz; Gruffydd-Jones, Tim; Hartmann, Katrin; Horzinek, Marian C; Hosie, Margaret J; Marsilio, Fulvio; Lloret, Albert; Lutz, Hans; Pennisi, Maria Grazia; Radford, Alan D; Thiry, Etienne; Truyen, Uwe; Möstl, Karin

    2015-07-01

    West Nile virus (WNV) is a zoonotic mosquito-borne virus with a broad host range that infects mainly birds and mosquitos, but also mammals (including humans), reptiles, amphibians and ticks. It is maintained in a bird-mosquito-bird transmission cycle. The most important vectors are bird-feeding mosquitos of the Culex genus; maintenance and amplification mainly involve passerine birds. WNV can cause disease in humans, horses and several species of birds following infection of the central nervous system. Cats can also be infected through mosquito bites, and by eating infected small mammals and probably also birds. Although seroprevalence in cats can be high in endemic areas, clinical disease and mortality are rarely reported. If a cat is suspected of clinical signs due to an acute WNV infection, symptomatic treatment is indicated. © Published by SAGE on behalf of ISFM and AAFP 2015.

  11. Vaccines and immunotherapeutics for the prevention and treatment of infections with West Nile virus.

    PubMed

    Beasley, David W C

    2011-02-01

    The emergence of West Nile virus (WNV) in North America in 1999 as a cause of severe neurological disease in humans, horses and birds stimulated development of vaccines for human and veterinary use, as well as polyclonal/monoclonal antibodies and other immunomodulating compounds for use as therapeutics. Although disease incidence in North America has declined since the peak epidemics in 2002-2003, the virus has continued to be annually transmitted in the Americas and to cause periodic epidemics in Europe and the Middle East. Continued transmission of the virus with human and animal disease suggests that vaccines and therapeutics for the prevention and treatment of WNV disease could be of great benefit. This article focuses on progress in development and evaluation of vaccines and immunotherapeutics for the prevention and treatment of WNV disease in humans and animals.

  12. Immunogenicity of West Nile virus infectious DNA and its noninfectious derivatives

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Seregin, Alexey; Nistler, Ryan; Borisevich, Victoria

    2006-12-20

    The exceptionally high virulence of the West Nile NY99 strain makes its suitability in the development of a live WN vaccine uncertain. The aim of this study is to investigate the immunogenicity of noninfectious virus derivatives carrying pseudolethal mutations, which preclude virion formation without affecting preceding steps of the viral infectious cycle. When administered using DNA immunization, such constructs initiate an infectious cycle but cannot lead to a viremia. While the magnitude of the immune response to a noninfectious replication-competent construct was lower than that of virus or infectious DNA, its overall quality and the protective effect were similar. Inmore » contrast, a nonreplicating construct of similar length induced only a marginally detectable immune response in the dose range used. Thus, replication-competent noninfectious constructs derived from infectious DNA may offer an advantageous combination of the safety of noninfectious formulations with the quality of the immune response characteristic of infectious vaccines.« less

  13. Discovering spatio-temporal models of the spread of West Nile virus.

    PubMed

    Orme-Zavaleta, Jennifer; Jorgensen, Jane; D'Ambrosio, Bruce; Altendorf, Eric; Rossignol, Philippe A

    2006-04-01

    Emerging infectious diseases are characterized by complex interactions among disease agents, vectors, wildlife, humans, and the environment. Since the appearance of West Nile virus (WNV) in New York City in 1999, it has infected over 8,000 people in the United States, resulting in several hundred deaths in 46 contiguous states. The virus is transmitted by mosquitoes and maintained in various bird reservoir hosts. Its unexpected introduction, high morbidity, and rapid spread have left public health agencies facing severe time constraints in a theory-poor environment, dependent largely on observational data collected by independent survey efforts and much uncertainty. Current knowledge may be expressed as a priori constraints on models learned from data. Accordingly, we applied a Bayesian probabilistic relational approach to generate spatially and temporally linked models from heterogeneous data sources. Using data collected from multiple independent sources in Maryland, we discovered the integrated context in which infected birds are plausible indicators for positive mosquito pools and human cases for 2001 and 2002.

  14. Crow deaths as a sentinel surveillance system for West Nile virus in the northeastern United States, 1999

    USGS Publications Warehouse

    Eidson, M.; Komar, N.; Sorhage, F.; Nelson, R.; Talbot, T.; Mostashari, F.; McLean, R.; ,

    2001-01-01

    In addition to human encephalitis and meningitis cases, the West Nile (WN) virus outbreak in the summer and fall of 1999 in New York State resulted in bird deaths in New York, New Jersey, and Connecticut. From August to December 1999, 295 dead birds were laboratory-confirmed with WN virus infection; 262 (89%) were American Crows (Corvus brachyrhynchos). The New York State Department of Health received reports of 17,339 dead birds, including 5,697 (33%) crows; in Connecticut 1,040 dead crows were reported. Bird deaths were critical in identifying WN virus as the cause of the human outbreak and defining its geographic and temporal limits. If established before a WN virus outbreak, a surveillance system based on bird deaths may provide a sensitive method of detecting WN virus.

  15. Climatic, ecological, and socioeconomic factors associated with West Nile virus incidence in Atlanta, Georgia, U.S.A.

    Treesearch

    Graeme Lockaby; Navideh Noori; Wayde Morse; Wayne Zipperer; Latif Kalin; Robin Governo; Rajesh Sawant; Matthew Ricker

    2016-01-01

    The integrated effects of the many risk factors associated with West Nile virus (WNV) incidence are complex and notwell understood. We studied an array of risk factors in and around Atlanta, GA, that have been shown to be linked with WNV inother locations. This array was comprehensive and included climate and meteorological metrics, vegetation...

  16. West Nile Virus Infection in Human and Mouse Cornea Tissue

    PubMed Central

    Blitvich, Bradley J.; Wang, Tian; Saxena, Vandana; Zeng, Shemin; Harmon, Karen M.; Raymond, Matthew D.; Goins, Kenneth M.; Reed, Cynthia R.; Mullins, Robert F.; Greiner, Mark A.

    2016-01-01

    The purpose of this study was to determine the in vitro and ex vivo susceptibility of human corneal cells to West Nile virus (WNV) infection and evaluate the ability of the virus to disseminate to the corneas of infected mice. Human corneal epithelial cells were challenged with WNV, incubated for 1–6 days, and tested for evidence of WNV infection. Viral RNA and antigen were detected at every time point, and the virus reached a peak titer of 2.5 × 107 plaque-forming units (pfu)/mL at 3 days postinoculation (PI). Corneas procured from donors were incubated in culture dishes containing WNV for 1–5 days and tested for evidence of WNV. Viral RNA and antigen were detected, and the virus reached a mean peak titer of 4.9 × 104 pfu/mL at 5 days PI. Mice were inoculated intraperitoneally with WNV, and their eyes were harvested at 2, 5, and 8 days PI and tested for evidence of WNV. Viral RNA was detected in corneas of four of nine systemically infected mice as early as 2 days PI. We conclude that human corneal cells support WNV replication in vitro and ex vivo, and WNV may disseminate into the corneas of experimentally infected mice. These findings indicate that corneal transmission cannot be ruled out as a novel mode of human-to-human WNV transmission and additional experiments should be conducted to assess this risk further. PMID:27672204

  17. West Nile Virus Surveillance in 2013 via Mosquito Screening in Northern Italy and the Influence of Weather on Virus Circulation

    PubMed Central

    Calzolari, Mattia; Pautasso, Alessandra; Montarsi, Fabrizio; Albieri, Alessandro; Bellini, Romeo; Bonilauri, Paolo; Defilippo, Francesco; Lelli, Davide; Moreno, Ana; Chiari, Mario; Tamba, Marco; Zanoni, Mariagrazia; Varisco, Giorgio; Bertolini, Silvia; Modesto, Paola; Radaelli, Maria Cristina; Iulini, Barbara; Prearo, Marino; Ravagnan, Silvia; Cazzin, Stefania; Mulatti, Paolo; Monne, Isabella; Bonfanti, Lebana; Marangon, Stefano; Goffredo, Maria; Savini, Giovanni; Martini, Simone; Mosca, Andrea; Farioli, Marco; Gemma Brenzoni, Laura; Palei, Manlio; Russo, Francesca; Natalini, Silvano; Angelini, Paola; Casalone, Cristina; Dottori, Michele; Capelli, Gioia

    2015-01-01

    West Nile virus (WNV) is a recently re-emerged health problem in Europe. In Italy, an increasing number of outbreaks of West Nile disease, with occurrences of human cases, have been reported since 2008. This is particularly true in northern Italy, where entomological surveillance systems have been implemented at a regional level. The aim of this study was to use, for the first time, all the entomological data collected in the five regions undergoing surveillance for WNV in northern Italy to characterize the viral circulation (at a spatial and temporal scale), identify potential mosquito vectors, and specify relationships between virus circulation and meteorological conditions. In 2013, 286 sites covering the entire Pianura Padana area were monitored. A total of 757,461 mosquitoes were sampled. Of these, 562,079 were tested by real-time PCR in 9,268 pools, of which 180 (1.9%) were positive for WNV. The largest part of the detected WNV sequences belonged to lineage II, demonstrating that, unlike those in the past, the 2013 outbreak was mainly sustained by this WNV lineage. This surveillance also detected the Usutu virus, a WNV-related flavivirus, in 241 (2.6%) pools. The WNV surveillance systems precisely identified the area affected by the virus and detected the viral circulation approximately two weeks before the occurrence of onset of human cases. Ninety percent of the sampled mosquitoes were Culex pipiens, and 178/180 WNV-positive pools were composed of only this species, suggesting this mosquito is the main WNV vector in northern Italy. A significantly higher abundance of the vector was recorded in the WNV circulation area, which was characterized by warmer and less rainy conditions and greater evapotranspiration compared to the rest of the Pianura Padana, suggesting that areas exposed to these conditions are more suitable for WNV circulation. This observation highlights warmer and less rainy conditions as factors able to enhance WNV circulation and cause virus

  18. West Nile Virus Surveillance in 2013 via Mosquito Screening in Northern Italy and the Influence of Weather on Virus Circulation.

    PubMed

    Calzolari, Mattia; Pautasso, Alessandra; Montarsi, Fabrizio; Albieri, Alessandro; Bellini, Romeo; Bonilauri, Paolo; Defilippo, Francesco; Lelli, Davide; Moreno, Ana; Chiari, Mario; Tamba, Marco; Zanoni, Mariagrazia; Varisco, Giorgio; Bertolini, Silvia; Modesto, Paola; Radaelli, Maria Cristina; Iulini, Barbara; Prearo, Marino; Ravagnan, Silvia; Cazzin, Stefania; Mulatti, Paolo; Monne, Isabella; Bonfanti, Lebana; Marangon, Stefano; Goffredo, Maria; Savini, Giovanni; Martini, Simone; Mosca, Andrea; Farioli, Marco; Gemma Brenzoni, Laura; Palei, Manlio; Russo, Francesca; Natalini, Silvano; Angelini, Paola; Casalone, Cristina; Dottori, Michele; Capelli, Gioia

    2015-01-01

    West Nile virus (WNV) is a recently re-emerged health problem in Europe. In Italy, an increasing number of outbreaks of West Nile disease, with occurrences of human cases, have been reported since 2008. This is particularly true in northern Italy, where entomological surveillance systems have been implemented at a regional level. The aim of this study was to use, for the first time, all the entomological data collected in the five regions undergoing surveillance for WNV in northern Italy to characterize the viral circulation (at a spatial and temporal scale), identify potential mosquito vectors, and specify relationships between virus circulation and meteorological conditions. In 2013, 286 sites covering the entire Pianura Padana area were monitored. A total of 757,461 mosquitoes were sampled. Of these, 562,079 were tested by real-time PCR in 9,268 pools, of which 180 (1.9%) were positive for WNV. The largest part of the detected WNV sequences belonged to lineage II, demonstrating that, unlike those in the past, the 2013 outbreak was mainly sustained by this WNV lineage. This surveillance also detected the Usutu virus, a WNV-related flavivirus, in 241 (2.6%) pools. The WNV surveillance systems precisely identified the area affected by the virus and detected the viral circulation approximately two weeks before the occurrence of onset of human cases. Ninety percent of the sampled mosquitoes were Culex pipiens, and 178/180 WNV-positive pools were composed of only this species, suggesting this mosquito is the main WNV vector in northern Italy. A significantly higher abundance of the vector was recorded in the WNV circulation area, which was characterized by warmer and less rainy conditions and greater evapotranspiration compared to the rest of the Pianura Padana, suggesting that areas exposed to these conditions are more suitable for WNV circulation. This observation highlights warmer and less rainy conditions as factors able to enhance WNV circulation and cause virus

  19. Experimental infection of Tilapia Lake Virus (TiLV) in Nile tilapia (Oreochromis niloticus) and red tilapia (Oreochromis spp.).

    PubMed

    Tattiyapong, Puntanat; Dachavichitlead, Worawan; Surachetpong, Win

    2017-08-01

    Since 2015, a novel orthomyxo-like virus, tilapia lake virus (TiLV) has been associated with outbreaks of disease and massive mortality of cultured Nile and red tilapia (Oreochromis niloticus and Oreochromis spp., respectively) in Thailand. In this study, TiLV was isolated from field samples and propagated in the permissive E-11 cell line, with cytopathic effect (CPE) development within 3-5days post-inoculation. Electron micrographs of infected E-11 cells and fish tissues confirmed the rounded, enveloped virions of 60 to 80nm with characteristics very similar to those of Orthomyxoviridae. In vivo challenge studies showed that high mortality in Nile (86%) and red tilapia (66%) occurred within 4-12days post-infection. The virus was re-isolated from challenged fish tissues in the permissive cell line, and PCR analysis confirmed TiLV as a causative pathogen. The distinct histopathology of challenged fish included massive degeneration and inflammatory cell infiltration in the liver and brain as well as the presence of eosinophilic intracytoplasmic inclusions in hepatocytes and splenic cells. Our results fulfilled Koch's postulates and confirmed that TiLV is an etiologic agent of mass mortality of tilapia in Thailand. The emergence of this virus in many countries has helped increase awareness that it is a potential threat to tilapia aquacultured in Thailand, Asia, and worldwide. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. The West Nile virus assembly process evades the conserved antiviral mechanism of the interferon-induced MxA protein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hoenen, Antje; Gillespie, Leah; Department of Microbiology and Immunology, University of Melbourne, Melbourne

    2014-01-05

    Flaviviruses have evolved means to evade host innate immune responses. Recent evidence suggests this is due to prevention of interferon production and signaling in flavivirus-infected cells. Here we show that the interferon-induced MxA protein can sequester the West Nile virus strain Kunjin virus (WNV{sub KUN}) capsid protein in cytoplasmic tubular structures in an expression-replication system. This sequestering resulted in reduced titers of secreted WNV{sub KUN} particles. We show by electron microscopy, tomography and 3D modeling that these cytoplasmic tubular structures form organized bundles. Additionally we show that recombinant ER-targeted MxA can restrict production of infectious WNV{sub KUN} under conditions ofmore » virus infection. Our results indicate a co-ordinated and compartmentalized WNV{sub KUN} assembly process may prevent recognition of viral components by MxA, particularly the capsid protein. This recognition can be exploited if MxA is targeted to intracellular sites of WNV{sub KUN} assembly. This results in further understanding of the mechanisms of flavivirus evasion from the immune system. - Highlights: • We show that the ISG MxA can recognize the West Nile virus capsid protein. • Interaction between WNV C protein and MxA induces cytoplasmic fibrils. • MxA can be retargeted to the ER to restrict WNV particle release. • WNV assembly process is a strategy to avoid MxA recognition.« less

  1. Potential for Waterborne and Invertebrate Transmission of West Nile Virus in the Great Salt Lake, Utah.

    PubMed

    Lund, Melissa; Shearn-Bochsler, Valerie; Dusek, Robert J; Shivers, Jan; Hofmeister, Erik

    2017-07-15

    In November and December of 2013, a large mortality event involving 15,000 to 20,000 eared grebes ( Podiceps nigricollis ) occurred at the Great Salt Lake (GSL), UT. The onset of the outbreak in grebes was followed by a mortality event in >86 bald eagles ( Haliaeetus leucocephalus ). During the die-off, West Nile virus (WNV) was detected by reverse transcription-PCR (RT-PCR) or viral culture in the carcasses of grebes and eagles submitted to the National Wildlife Health Center. However, no activity of mosquitoes, the primary vectors of WNV, was detected by the State of Utah's WNV monitoring program. The transmission of WNV has rarely been reported during the winter in North America in the absence of known mosquito activity; however, the size of this die-off, the habitat in which it occurred, and the species involved are unique. We experimentally investigated whether WNV could survive in water with a high salt content, as found at the GSL, and whether brine shrimp, the primary food of migrating eared grebes on the GSL, could have played a role in the transmission of WNV to feeding birds. We found that WNV can survive up to 72 h at 4°C in water containing 30 to 150 ppt NaCl, and brine shrimp incubated with WNV in 30 ppt NaCl may adsorb WNV to their cuticle and, through feeding, infect epithelial cells of their gut. Both mechanisms may have potentiated the WNV die-off in migrating eared grebes on the GSL. IMPORTANCE Following a major West Nile virus die-off of eared grebes and bald eagles at the Great Salt Lake (GSL), UT, in November to December 2013, this study assessed the survival of West Nile virus (WNV) in water as saline as that of the GSL and whether brine shrimp, the major food for migrating grebes, could have played a role as a vector for the virus. While mosquitoes are the major vector of WNV, under certain circumstances, transmission may occur through contaminated water and invertebrates as food. Copyright © 2017 American Society for Microbiology.

  2. The Structural Immunology of Antibody Protection against West Nile Virus

    PubMed Central

    Diamond, Michael S.; Pierson, Theodore C.; Fremont, Daved H.

    2009-01-01

    Summary Recent investigations of the interaction between the West Nile virus (WNV) envelope protein (E) and monoclonal antibodies (mAbs) have elucidated fundamental insights into the molecular mechanisms of neutralization. Structural studies have defined an epitope on the lateral ridge of domain III (DIII-lr) of the WNV E protein that is recognized by antibodies with the strongest neutralizing activity in vitro and in vivo. Antibodies that bind this epitope are highly potent because they efficiently block at a post-entry step of viral infection with relatively low virion occupancy requirements. In this review, we will discuss the structural, molecular, and immunologic basis for antibody-mediated protection against WNV, and its implications for novel therapeutic or vaccine strategies. PMID:18837784

  3. Seroprevalence of West Nile Virus in Wild Birds in Far Eastern Russia Using a Focus Reduction Neutralization Test

    PubMed Central

    Murata, Ryo; Hashiguchi, Kazuaki; Yoshii, Kentaro; Kariwa, Hiroaki; Nakajima, Kensuke; Ivanov, Leonid I.; Leonova, Galina N.; Takashima, Ikuo

    2011-01-01

    West Nile (WN) virus has been spreading geographically to non-endemic areas in various parts of the world. However, little is known about the extent of WN virus infection in Russia. Japanese encephalitis (JE) virus, which is closely related to WN virus, is prevalent throughout East Asia. We evaluated the effectiveness of a focus reduction neutralization test in young chicks inoculated with JE and WN viruses, and conducted a survey of WN infection among wild birds in Far Eastern Russia. Following single virus infection, only neutralizing antibodies specific to the homologous virus were detected in chicks. The neutralization test was then applied to serum samples from 145 wild birds for WN and JE virus. Twenty-one samples were positive for neutralizing antibodies to WN. These results suggest that WN virus is prevalent among wild birds in the Far Eastern region of Russia. PMID:21363987

  4. MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis.

    PubMed

    Zhao, Jincun; Vijay, Rahul; Zhao, Jingxian; Gale, Michael; Diamond, Michael S; Perlman, Stanley

    2016-08-15

    West Nile virus (WNV) is the most important cause of epidemic encephalitis in North America. Innate immune responses, which are critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors, RIG-I and MDA5, and their downstream adaptor molecule, MAVS. Here, we show that a deficiency of MAVS in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In Mavs(-/-) mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were polyfunctional and lysed peptide-pulsed target cells in vitro However, virus-specific T cells in the brains of infected Mavs(-/-) mice exhibited lower functional avidity than those in wild-type animals, and even virus-specific memory T cells generated by prior immunization could not protect Mavs(-/-) mice from WNV-induced lethal disease. Concomitant with ineffective virus clearance, macrophage numbers were increased in the Mavs(-/-) brain, and both macrophages and microglia exhibited an activated phenotype. Microarray analyses of leukocytes in the infected Mavs(-/-) brain showed a preferential expression of genes associated with activation and inflammation. Together, these results demonstrate a critical role for MAVS in hematopoietic cells in augmenting the kinetics of WNV clearance and thereby preventing a dysregulated and pathogenic immune response. West Nile virus (WNV) is the most important cause of mosquito-transmitted encephalitis in the United States. The innate immune response is known to be critical for protection in infected mice. Here, we show that expression of MAVS, a key adaptor molecule in the RIG-I-like receptor RNA-sensing pathway, in hematopoietic cells is critical for protection from lethal WNV infection. In the absence of MAVS, there is a massive infiltration of myeloid cells and virus-specific T cells into the brain and overexuberant

  5. Antibodies to West Nile virus in wild and farmed crocodiles in southeastern Mexico.

    PubMed

    Machain-Williams, Carlos; Padilla-Paz, Sergio E; Weber, Manuel; Cetina-Trejo, Rosa; Juarez-Ordaz, José Alfredo; Loroño-Pino, María Alba; Ulloa, Armando; Wang, Chong; Garcia-Rejon, Julián; Blitvich, Bradley J

    2013-07-01

    Surveillance for evidence of West Nile virus (WNV) infection in Morelet's crocodiles (Crocodylus moreletii) was conducted in Campeche State, Mexico, in 2007. Sera from 62 crocodiles (32 free-ranging and 30 captive) were assayed for antibodies to WNV by epitope-blocking enzyme-linked immunosorbent assay. Antibodies to WNV were detected in 13 (41%) wild and nine (30%) captive crocodiles, and the overall antibody prevalence was 35%. Although evidence of WNV infection in captive crocodiles has been reported in Mexico, we provide the first evidence of WNV exposure in wild crocodiles in Mexico.

  6. Antibodies to West Nile Virus in Wild and Farmed Crocodiles in Southeastern Mexico

    PubMed Central

    Machain-Williams, Carlos; Padilla-Paz, Sergio E.; Weber, Manuel; Cetina-Trejo, Rosa; Juarez-Ordaz, José Alfredo; Loroño-Pino, María Alba; Ulloa, Armando; Wang, Chong; Garcia-Rejon, Julián; Blitvich, Bradley J.

    2013-01-01

    Surveillance for evidence of West Nile virus (WNV) infection in Morelet’s crocodiles (Crocodylus moreletii) was conducted in Campeche State, Mexico, in 2007. Sera from 62 crocodiles (32 free-ranging and 30 captive) were assayed for antibodies to WNV by epitope-blocking enzyme-linked immunosorbent assay. Antibodies to WNV were detected in 13 (41%) wild and nine (30%) captive crocodiles, and the overall antibody prevalence was 35%. Although evidence of WNV infection in captive crocodiles has been reported in Mexico, we provide the first evidence of WNV exposure in wild crocodiles in Mexico. PMID:23778623

  7. Human West Nile Virus Disease Outbreak in Pakistan, 2015–2016

    PubMed Central

    Khan, Erum; Barr, Kelli L.; Farooqi, Joveria Qais; Prakoso, Dhani; Abbas, Alizae; Khan, Zain Y.; Ashi, Shanze; Imtiaz, Kehkashan; Aziz, Z.; Malik, Faisal; Lednicky, John A.; Long, Maureen T.

    2018-01-01

    Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological disease in human patients in this country. Of 997 enrolled patients presenting with clinical features suggestive of arboviral disease, 105 were positive for WNV IgM antibodies, and 71 of these patients possessed WNV-specific neutralizing antibodies. Cross-reactivity of WNV IgM antibodies with Japanese encephalitis virus (JEV) occurred in 75 of these 105 patients. WNV co-infections with Dengue viruses were not a contributing factor for the severity of disease. Nor did prior exposure to dengue virus contribute to incidence of neurological involvement in WNV-infected patients. Patients with WNV infections were more likely to present with altered mental status, seizures, and reduced Glasgow Coma scores when compared with JEV-infected patients. Human WNV cases and vector numbers exhibited a temporal correlation with climate. PMID:29535994

  8. Hydrologic variability and the dynamics of West Nile virus transmission

    NASA Astrophysics Data System (ADS)

    Shaman, J. L.

    2011-12-01

    West Nile virus (WNV) first emerged in North America in New York City during 1999 and since that time has spread throughout the continent and settled into a pattern of local endemicity in which outbreaks of variable size develop in some years but not others. Predicting where and when these outbreaks will develop is an issue of considerable public health importance. Spillover transmission of WNV to humans typically occurs when infection rates among vector mosquitoes are elevated. Mosquito infection rates are not constant through time but instead increase when newly emergent mosquitoes can more readily acquire WNV by blood-meal feeding on available, infected animal hosts. Such an increase of vector mosquito infection rates is termed amplification and is facilitated for WNV by intense zoonotic transmission of the virus among vector mosquitoes and avian hosts. Theory, observation and model simulations indicate that amplification is favored when mosquito breeding habitats and bird nesting and roosting habitats overlap. Both vector mosquitoes and vertebrate hosts depend on water resources; mosquitoes are critically dependent on the availability of standing water, as the first 3 stages of the mosquito life cycle, egg, larvae, pupae, are aquatic. Here it is shown that hydrologic variability often determines where and when vector mosquitoes and avian hosts congregate together, and when the amplification of WNV is more likely. Measures of land surface wetness and pooling, from ground observation, satellite observation, or numerical modeling, can provide reliable estimates of where and when WNV transmission hotspots will arise. Examples of this linkage between hydrology and WNV activity are given for Florida, Colorado and New York, and an operational system for monitoring and forecasting WNV risk in space and time is presented for Florida.

  9. West Nile Flavivirus Polioencephalomyelitis in a harbor seal (Phoca vitulina).

    PubMed

    Del Piero, F; Stremme, D W; Habecker, P L; Cantile, C

    2006-01-01

    A 12-year-old male harbor seal presented with progressive signs of neurologic dysfunction including head tremors, muzzle twitching, clonic spasms, and weakness. Lesions included polioencephalomyelitis with glial nodules, spheroids, neuronophagia, ring hemorrhages, and a few neutrophils. Neurons, fibers, and glial nodules were multifocally colonized with intracytoplasmic West Nile flavivirus antigens that were demonstrated using indirect immunohistochemical analysis. Flavivirus on cultured cells also was isolated and was identified by use of monoclonal antibodies and reverse transcriptase-polymerase chain reaction analysis. Clinical signs of disease and lesion morphology and distribution were similar to those of equine West Nile virus infection. Similar to horses, alpacas, humans, dogs, and reptiles, seals can be dead-end hosts of West Nile virus.

  10. West Nile virus among hospitalized, febrile patients: a case for expanding diagnostic testing.

    PubMed

    Whitney, Ellen A Spotts; Heilpern, Katherine L; Woods, Christopher W; Bahn, C Christina; Franko, Elizabeth A; Del Rio, Carlos; Silk, Benjamin J; Ratcliff, Jonathan J; Bryant, Katherine A; Park, Mahin M; Watkins, Sandra J; Caram, Lauren B; Blumberg, Henry M; Berkelman, Ruth L

    2006-01-01

    In Georgia, most individuals reported with West Nile virus (WNV) disease have been diagnosed with West Nile neuroinvasive disease (WNND). Relatively few cases of West Nile Fever (WNF) are reported, and the burden of illness due to WNV is likely underestimated. From July through October 2003, WNV serologic testing was performed on enrolled patients>or=18 years of age with fever admitted to a large, urban hospital in Atlanta, Georgia through the emergency department (ED). Patients' history, clinical, and laboratory data were recorded. Residual blood drawn in the ED was tested to determine the presence of WNV IgG and IgM antibodies. Of 254 patients tested for WNV, four (1.6%) patients were positive for WNV IgM and IgG antibodies, and had a clinical illness compatible with WNV. None of the four positive patients were clinically suspected of having WNV infection; discharge diagnoses included pneumonia, migraine, stroke, and gout. These four patients accounted for 80% of all WNV diagnosed in this hospital, 44% of all cases in Fulton County, and 7% of all cases reported in Georgia in 2003. The occurrence of WNV disease may be substantially greater than currently reflected in disease statistics in Georgia and many other states. When indicators of WNV activity are present and patients are likely to have had intensive mosquito exposure, WNV should be considered in the differential diagnosis of seriously ill, febrile patients.

  11. Review of West Nile virus circulation and outbreak risk in Madagascar: Entomological and ornithological perspectives.

    PubMed

    Tantely, Michaël Luciano; Goodman, Steven M; Rakotondranaivo, Tsirinaina; Boyer, Sébastien

    2016-01-01

    West Nile fever (WNF) is a zoonotic disease, occurring nearly globally. In Madagascar, West Nile virus (WNV) was first detected in 1978 from wild birds and the virus is currently distributed across the island, but no epidemic or epizootic period has been recorded. One fatal human case of WNV infection was reported in 2011, suggesting a "tip of the iceberg" phenomenon of a possible WNF epidemic/epizootic on the island. The main objective of this literature-based survey is to review patterns of WNV circulation in Madagascar from the entomological and ornithological points of view. Among the 235 mosquito species described from Madagascar, 29 species are widely associated with WNV infection; 16 of them are found naturally infected with WNV on the island and categorized into major, candidate, and potential vectors of WNV according to their vector capacity. This study upholds the hypothesis that WNV enzooticity is independent of annual movements of migratory birds passing through Madagascar. Moreover, the lack of regular migratory bird flux between Africa and Madagascar would reduce the probability of transmission and the subsequent reintroduction of the virus into locally occurring mosquito species. Given that Palearctic migratory birds are strongly implicated in the transmission of WNV, we highlight notable differences in the movements and species diversity of these birds in Madagascar as compared to eastern and northern Africa. Risk factors from this two-pronged approach are presented for the emergence of WNF outbreak. © M.L. Tantely et al., published by EDP Sciences, 2016.

  12. Contributions to integrative knowledge of West Nile virus reported in Romania - methods and tools for managing health-environment relationship at different spatial and temporal scales

    NASA Astrophysics Data System (ADS)

    Baltesiu, L.; Gomoiu, M. T.; Mudura, R.; Nicolescu, G.; Purcarea-Ciulacu, V.

    2012-04-01

    After 1990 there were environmental changes at national, European and global level which led to the emergence and re-emergence of infectious diseases. Among these diseases, those transmitted by vectors were installed on very large areas where pathogens entered the complex transmission cycles within the local ecosystems. Environmental changes were generated by climatic (temperature and precipitation), geomorphologic (altitude) and anthropogenic (land cover / land use) changes. Due to these environmental changes it became necessary to anticipate, prevent and control the epidemics in order to avoid major crises of natural and socio-economic systems. In these circumstances, the risk of re-emergence of West Nile virus infection increased, thus becoming a public health problem for Romania. Our research consisted in assessing this risk, depending on environmental changes that can influence the presence and space-time distribution as well as the dynamics of the elements of virus transmission cycle. Study areas were selected so that they should meet, on the one hand, very different natural ecosystems and on the other hand should include continuously changing anthropogenic ecosystems that provide optimal conditions for the vector-borne West Nile virus. These areas were: the Danube Delta including Razim-Sinoe complex (Tulcea County), Bucharest Metropolitan Area (BMA) (Bucharest and Ilfov & Giurgiu Counties). The Danube Delta lagoon area is the gateway to West Nile virus in Romania. During the neurological infection epidemic with West Nile virus in 1996, in BMA were recorded 60% of the total number of human cases. For the period 2009 - 2011 the authors developed risk maps to West Nile virus vectors to vertebrate hosts depending on climatic, geomorphologic and anthropogenic changes. Maps were made using ArcGis - ArcMap software, depending on the mean annual temperature and precipitation. We were used by the altitude risk map the hypsographic map of Romania and for the risk map

  13. A phylogenetic approach to following West Nile virus in Connecticut

    PubMed Central

    Anderson, John F.; Vossbrinck, Charles R.; Andreadis, Theodore G.; Iton, Anthony; Beckwith, William H.; Mayo, Donald R.

    2001-01-01

    The 1999 outbreak of West Nile (WN) virus in the northeastern United States was the first known natural occurrence of this flavivirus in the Western Hemisphere. In 1999 and 2000, 82 independent Connecticut WN virus isolates were cultured from nine species of birds, five species of mosquitoes, and one striped skunk. Nucleotide sequences obtained from these isolates identified 30 genetic changes, compared with WN-NY99, in a 921-nt region of the viral genome beginning at nucleotide position 205 and ending at 1125. This region encodes portions of the nucleocapsid and envelope proteins and includes the entire coding regions for the premembrane and membrane proteins. Amino acid changes occurred at seven loci in six isolates relative to the WN-NY99 strain. Although 34 of the isolates showed sequences identical to the WN-NY99 isolate, we were able to show geographical-based clusters of mutations. In particular, 26 isolates were characterized by mutation of C to T at position 858. This group apparently originated in Stamford, CT and disseminated to sites located as far as 54 miles from Stamford. Sequences of WN virus isolated from both brain and heart tissues from the same avian host were identical in all 14 tested individual birds, suggesting that the mutations we have documented are real and not caused by culture, RNA extraction, or PCR procedures. We conclude that this portion of the viral genome will enable us to follow the geographical and temporal movement of variant WN virus strains as they adapt to North America. PMID:11606791

  14. West Nile Virus Infection in Human and Mouse Cornea Tissue.

    PubMed

    Blitvich, Bradley J; Wang, Tian; Saxena, Vandana; Zeng, Shemin; Harmon, Karen M; Raymond, Matthew D; Goins, Kenneth M; Reed, Cynthia R; Mullins, Robert F; Greiner, Mark A

    2016-11-02

    The purpose of this study was to determine the in vitro and ex vivo susceptibility of human corneal cells to West Nile virus (WNV) infection and evaluate the ability of the virus to disseminate to the corneas of infected mice. Human corneal epithelial cells were challenged with WNV, incubated for 1-6 days, and tested for evidence of WNV infection. Viral RNA and antigen were detected at every time point, and the virus reached a peak titer of 2.5 × 10 7 plaque-forming units (pfu)/mL at 3 days postinoculation (PI). Corneas procured from donors were incubated in culture dishes containing WNV for 1-5 days and tested for evidence of WNV. Viral RNA and antigen were detected, and the virus reached a mean peak titer of 4.9 × 10 4 pfu/mL at 5 days PI. Mice were inoculated intraperitoneally with WNV, and their eyes were harvested at 2, 5, and 8 days PI and tested for evidence of WNV. Viral RNA was detected in corneas of four of nine systemically infected mice as early as 2 days PI. We conclude that human corneal cells support WNV replication in vitro and ex vivo, and WNV may disseminate into the corneas of experimentally infected mice. These findings indicate that corneal transmission cannot be ruled out as a novel mode of human-to-human WNV transmission and additional experiments should be conducted to assess this risk further. © The American Society of Tropical Medicine and Hygiene.

  15. Characterization of West Nile Viruses Isolated from Captive American Flamingoes (Phoenicopterus ruber) in Medellin, Colombia

    PubMed Central

    Osorio, Jorge E.; Ciuoderis, Karl A.; Lopera, Juan G.; Piedrahita, Leidy D.; Murphy, Darby; LeVasseur, James; Carrillo, Lina; Ocampo, Martha C.; Hofmeister, Erik

    2012-01-01

    Serum samples from a total of 71 healthy captive birds belonging to 18 species were collected in July of 2008 in Medellin (Colombia) and tested for flaviviruses. Eighteen of 29 samples from American Flamingoes (Phoenicopterus ruber) were positive for West Nile virus (WNV) by reverse transcription-polymerase chain reaction. Selected positive samples were serially passaged and WNV was confirmed by immunofluorescence. Two isolates (524/08, 9835/08) were characterized in vitro and in vivo. Sequence analysis revealed WNV with 16 nucleotide substitutions resulting in six amino acid changes when compared with the NY99 strain. Colombian (COL) viruses were more closely related to Louisiana isolates from 2001. When compared with attenuated strains isolated from Texas, COL isolates differed in their plaque size and temperature sensitivity phenotype. The COL viruses were pathogenic in embryonated chicken eggs and Balb/c mice. PMID:22802436

  16. Characterization of West Nile viruses isolated form captive American flamingoes (Phoenicopterus ruber) in Medellin, Colombia.

    USGS Publications Warehouse

    Osorio, Jorge E.; Ciuoderis, Karl A.; Lopera, Juan G.; Piedrahita, Leidy D.; Murphy, Darby; LeVasseur, James; Carrillo, Lina; Ocampo, Martha C.; Hofmeister, Erik

    2012-01-01

    Serum samples from a total of 71 healthy captive birds belonging to 18 species were collected in July of 2008 in Medellin (Colombia) and tested for flaviviruses. Eighteen of 29 samples from American Flamingoes (Phoenicopterus ruber) were positive for West Nile virus (WNV) by reverse transcription-polymerase chain reaction. Selected positive samples were serially passaged and WNV was confirmed by immunofluorescence. Two isolates (524/08, 9835/08) were characterized in vitro and in vivo. Sequence analysis revealed WNV with 16 nucleotide substitutions resulting in six amino acid changes when compared with the NY99 strain. Colombian (COL) viruses were more closely related to Louisiana isolates from 2001. When compared with attenuated strains isolated from Texas, COL isolates differed in their plaque size and temperature sensitivity phenotype. The COL viruses were pathogenic in embryonated chicken eggs and Balb/c mice.

  17. A Survey on West Nile and Usutu Viruses in Horses and Birds in Poland.

    PubMed

    Bażanów, Barbara; Jansen van Vuren, Petrus; Szymański, Piotr; Stygar, Dominika; Frącka, Agnieszka; Twardoń, Jan; Kozdrowski, Roland; Pawęska, Janusz T

    2018-02-17

    West Nile virus (WNV) and Usutu virus (USUV) are members of the family Flaviviridae which, natural life cycles involve mosquito-bird-mosquito transmission. Both represent emerging viruses in Europe with potential to cause neuroinvasive disease in humans. This study investigates the seroprevalence of serum neutralizing antibodies to WNV and to USUV in birds and in horses in Poland. Antibodies against WNV and USUV were detected in 5 (35.7%) and in 1 (7.14%) of 14 birds and in 62 (15.08%) and in 115 (27.98%) of 411 horses, respectively. Twenty-one WNV serologically positive horses (33.87%) and 67 USUV serologically positive horses (58.26%) did not travel outside Polish borders. Given the high abundance of potentially competent mosquito species in Poland, high populations of horses and different bird species, our findings highlight implementation of active control programs, including monitoring of geographic spread and dynamics of WNV and USUV transmission in both primary and accidental hosts. It is also important to improve public health awareness about the disease these viruses may cause.

  18. A Survey on West Nile and Usutu Viruses in Horses and Birds in Poland

    PubMed Central

    Bażanów, Barbara; Szymański, Piotr; Stygar, Dominika; Frącka, Agnieszka; Twardoń, Jan; Kozdrowski, Roland

    2018-01-01

    West Nile virus (WNV) and Usutu virus (USUV) are members of the family Flaviviridae which, natural life cycles involve mosquito–bird–mosquito transmission. Both represent emerging viruses in Europe with potential to cause neuroinvasive disease in humans. This study investigates the seroprevalence of serum neutralizing antibodies to WNV and to USUV in birds and in horses in Poland. Antibodies against WNV and USUV were detected in 5 (35.7%) and in 1 (7.14%) of 14 birds and in 62 (15.08%) and in 115 (27.98%) of 411 horses, respectively. Twenty-one WNV serologically positive horses (33.87%) and 67 USUV serologically positive horses (58.26%) did not travel outside Polish borders. Given the high abundance of potentially competent mosquito species in Poland, high populations of horses and different bird species, our findings highlight implementation of active control programs, including monitoring of geographic spread and dynamics of WNV and USUV transmission in both primary and accidental hosts. It is also important to improve public health awareness about the disease these viruses may cause. PMID:29462983

  19. Generation of West Nile virus infectious clones containing amino acid insertions between capsid and capsid anchor.

    PubMed

    Vandergaast, Rianna; Hoover, Lisa I; Zheng, Kang; Fredericksen, Brenda L

    2014-04-09

    West Nile virus (WNV) is a positive-sense RNA arbovirus responsible for recent outbreaks of severe neurological disease within the US and Europe. Large-scale analyses of antiviral compounds that inhibit virus replication have been limited due to the lack of an adequate WN reporter virus. Previous attempts to insert a reporter into the 3' untranslated region of WNV generated unstable viruses, suggesting that this region does not accommodate additional nucleotides. Here, we engineered two WNV infectious clones containing insertions at the Capsid (C)/Capsid Anchor (CA) junction of the viral polyprotein. Recombinant viruses containing a TAT(1-67) or Gaussia Luciferase (GLuc) gene at this location were successfully recovered. However, rapid loss of most, if not all, of the reporter sequence occurred for both viruses, indicating that the reporter viruses were not stable. While the GLuc viruses predominantly reverted back to wild-type WNV length, the TAT viruses retained up to 75 additional nucleotides of the reporter sequence. These additional nucleotides were stable over at least five passages and did not significantly alter WNV fitness. Thus, the C/CA junction of WNV can tolerate additional nucleotides, though insertions are subject to certain constraints.

  20. Generation of West Nile Virus Infectious Clones Containing Amino Acid Insertions Between Capsid and Capsid Anchor

    PubMed Central

    Vandergaast, Rianna; Hoover, Lisa I.; Zheng, Kang; Fredericksen, Brenda L.

    2014-01-01

    West Nile virus (WNV) is a positive-sense RNA arbovirus responsible for recent outbreaks of severe neurological disease within the US and Europe. Large-scale analyses of antiviral compounds that inhibit virus replication have been limited due to the lack of an adequate WN reporter virus. Previous attempts to insert a reporter into the 3’ untranslated region of WNV generated unstable viruses, suggesting that this region does not accommodate additional nucleotides. Here, we engineered two WNV infectious clones containing insertions at the Capsid (C)/Capsid Anchor (CA) junction of the viral polyprotein. Recombinant viruses containing a TAT(1-67) or Gaussia Luciferase (GLuc) gene at this location were successfully recovered. However, rapid loss of most, if not all, of the reporter sequence occurred for both viruses, indicating that the reporter viruses were not stable. While the GLuc viruses predominantly reverted back to wild-type WNV length, the TAT viruses retained up to 75 additional nucleotides of the reporter sequence. These additional nucleotides were stable over at least five passages and did not significantly alter WNV fitness. Thus, the C/CA junction of WNV can tolerate additional nucleotides, though insertions are subject to certain constraints. PMID:24721788

  1. Birds, migration and emerging zoonoses: west nile virus, lyme disease, influenza A and enteropathogens.

    PubMed

    Reed, Kurt D; Meece, Jennifer K; Henkel, James S; Shukla, Sanjay K

    2003-01-01

    Wild birds are important to public health because they carry emerging zoonotic pathogens, either as a reservoir host or by dispersing infected arthropod vectors. In addition, bird migration provides a mechanism for the establishment of new endemic foci of disease at great distances from where an infection was acquired. Birds are central to the epidemiology of West Nile virus (WNV) because they are the main amplifying host of the virus in nature. The initial spread of WNV in the U.S. along the eastern seaboard coincided with a major bird migration corridor. The subsequent rapid movement of the virus inland could have been facilitated by the elliptical migration routes used by many songbirds. A number of bird species can be infected with Borrelia burgdorferi, the etiologic agent of Lyme disease, but most are not competent to transmit the infection to Ixodes ticks. The major role birds play in the geographic expansion of Lyme disease is as dispersers of B. burgdorferi-infected ticks. Aquatic waterfowl are asymptomatic carriers of essentially all hemagglutinin and neuraminidase combinations of influenza A virus. Avian influenza strains do not usually replicate well in humans, but they can undergo genetic reassortment with human strains that co-infect pigs. This can result in new strains with a marked increase in virulence for humans. Wild birds can acquire enteropathogens, such as Salmonella and Campylobacter spp., by feeding on raw sewage and garbage, and can spread these agents to humans directly or by contaminating commercial poultry operations. Conversely, wild birds can acquire drug-resistant enteropathogens from farms and spread these strains along migration routes. Birds contribute to the global spread of emerging infectious diseases in a manner analogous to humans traveling on aircraft. A better understanding of avian migration patterns and infectious diseases of birds would be useful in helping to predict future outbreaks of infections due to emerging zoonotic

  2. Occlusive retinal vasculitis in a patient with West Nile virus.

    PubMed

    Teitelbaum, Bruce A; Newman, Tricia L; Tresley, David J

    2007-11-01

    West Nile virus (WNV) was first identified in the United States in 1999. In addition to a spectrum of systemic manifestations, several ocular conditions secondary to the virus have been reported, including chorioretinitis, uveitis and optic neuritis. Age and diabetes mellitus (DM) have been reported to be associated risk factors for the more severe forms of the systemic disease. Only seven cases of occlusive retinal vasculitis have been reported in patients with WNV infection. A 60-year-old Asian male presented with complaints of decreased vision in his left eye. He had been hospitalised approximately seven weeks earlier with meningo-encephalitis secondary to presumed WNV infection, at which time he was also diagnosed with DM. The visual loss coincided with the manifestation of systemic WNV infection. Old peripheral chorioretinal lesions without active inflammation in both eyes were consistent with WNV infection. In addition, retinal haemorrhage and cotton wool spots were noted in the posterior pole of both eyes with severe macular ischaemia in the left eye. Occlusive retinal vasculitis is an uncommon ocular manifestation of WNV, which should be suspected in patients with meningitis or encephalitis who reside in endemic areas with ocular findings of the disease.

  3. West Nile virus activity--United States, 2006.

    PubMed

    2007-06-08

    West Nile virus (WNV) is the leading cause of arboviral encephalitis in the United States. Originally discovered in Africa in 1937, WNV was first detected in the western hemisphere in 1999 in New York City. Since then, WNV has caused seasonal epidemics of febrile illness and severe neurologic disease in the United States. This report summarizes provisional WNV surveillance data for 2006 reported to CDC as of April 3, 2007. During 2006, WNV transmission to humans or animals expanded into 52 counties that had not previously reported transmission and recurred in 1,350 counties where transmission had been reported in previous years. In addition, 1,491 cases of WNV neuroinvasive disease (WNND) were reported in the United States during this period, amounting to a 14% increase from 2005 and the largest number reported since 2003. On the basis of extrapolations from past serosurveys, an estimated 41,750 cases of non-neuroinvasive WNV disease occurred in 2006; of these cases, 2,770 were reported. These findings highlight the need for ongoing surveillance, mosquito control, promotion of personal protection from mosquito bites, and research into additional prevention strategies.

  4. Differentiation of West Nile and St. Louis Encephalitis Virus Infections by Use of Noninfectious Virus-Like Particles with Reduced Cross-Reactivity▿ †

    PubMed Central

    Roberson, Jill A.; Crill, Wayne D.; Chang, Gwong-Jen J.

    2007-01-01

    Differential diagnosis of St. Louis encephalitis virus (SLEV) and West Nile virus (WNV) infections can be complicated due to the high degree of cross-reactivity observed in most serodiagnostic assays. In an effort to provide a more specific diagnostic test, we developed virus-like particle (VLP) antigens with reduced cross-reactivity for both SLEV and WNV by identifying and mutating envelope protein amino acids within the cross-reactive epitopes of VLP expression plasmids. To determine the serodiagnostic discriminatory ability of the antigens with reduced cross-reactivity, a panel of 134 human serum samples collected predominately from North American patients with SLEV or WNV infections was used to evaluate the performance of these novel antigens in imunoglobulin M antibody-capture enzyme-linked immunosorbent assays. Positive/negative ratios and the resulting diagnostic classifications were compared between the mutant and the wild-type (WT) VLPs. The mutant VLP antigens were more specific, with higher positive predictive values and higher likelihood ratios than the WT VLP antigens. Both the SLEV and WNV mutant VLPs greatly reduced the observed cross-reactivity, significantly increasing the specificity and sensitivity of the assay. The use of these novel VLP antigens with reduced cross-reactivity in these serodiagnostic assays and others should lead to more accurate diagnoses of current infections, thereby reducing the need for time-consuming and cumbersome confirmatory plaque-reduction neutralization tests to differentiate between SLEV and WNV infections in North America. PMID:17715375

  5. Culex Flavivirus During West Nile Virus Epidemic and Interepidemic Years in Chicago, United States.

    PubMed

    Newman, Christina M; Krebs, Bethany L; Anderson, Tavis K; Hamer, Gabriel L; Ruiz, Marilyn O; Brawn, Jeffrey D; Brown, William M; Kitron, Uriel D; Goldberg, Tony L

    2017-08-01

    Culex flavivirus (CxFV) is an insect-specific flavivirus infecting Culex mosquitoes, which are important vectors of West Nile virus (WNV). CxFV and WNV cocirculate in nature and coinfect Culex mosquitoes, including in a WNV "hotspot" in suburban Chicago. We previously identified a positive association between CxFV and WNV in mosquito pools collected from suburban Chicago in 2006. To further investigate this phenomenon, we compared the spatial and temporal distribution of CxFV during an interepidemic year (2011) and an epidemic year (2012) for WNV. Both viruses were more prevalent in mosquito pools in 2012 compared to 2011. During both years, the CxFV infection status of mosquito pools was associated with environmental factors such as habitat type and precipitation frequency rather than coinfection with WNV. These results support the idea that WNV and CxFV are ecologically associated, perhaps because both viruses respond to similar environmental drivers of mosquito populations.

  6. Specific interaction of capsid protein and importin-{alpha}/{beta} influences West Nile virus production

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bhuvanakantham, Raghavan; Chong, Mun-Keat; Ng, Mah-Lee, E-mail: micngml@nus.edu.sg

    2009-11-06

    West Nile virus (WNV) capsid (C) protein has been shown to enter the nucleus of infected cells. However, the mechanism by which C protein enters the nucleus is unknown. In this study, we have unveiled for the first time that nuclear transport of WNV and Dengue virus C protein is mediated by their direct association with importin-{alpha}. This interplay is mediated by the consensus sequences of bipartite nuclear localization signal located between amino acid residues 85-101 together with amino acid residues 42 and 43 of C protein. Elucidation of biological significance of importin-{alpha}/C protein interaction demonstrated that the binding efficiencymore » of this association influenced the nuclear entry of C protein and virus production. Collectively, this study illustrated the molecular mechanism by which the C protein of arthropod-borne flavivirus enters the nucleus and showed the importance of importin-{alpha}/C protein interaction in the context of flavivirus life-cycle.« less

  7. Role of communally nesting ardeid birds in the epidemiology of West Nile virus revisited.

    PubMed

    Reisen, William K; Wheeler, Sarah; Armijos, M Veronica; Fang, Ying; Garcia, Sandra; Kelley, Kara; Wright, Stan

    2009-06-01

    Although herons and egrets in the family Ardeidae frequently have been associated with viruses in the Japanese encephalitis virus serocomplex, communal nesting colonies do not appear to be a focus of early season and rapid amplification of West Nile virus (WNV) in California. Evidence for repeated WNV infection was found by testing living and dead nestlings collected under trees with mixed species ardeid colonies nesting above in an oak grove near the University of California arboretum in Davis and in a Eucalyptus grove at a rural farmstead. However, mosquito infection rates at both nesting sites were low and positive pools did not occur earlier than at comparison sites within the City of Davis or at the Yolo Bypass wetlands managed for rice production and waterfowl habitat. Black-crowned night herons (Nycticorax nycticorax) were the most abundant and frequently infected ardeid species, indicating that WNV may be an important cause of mortality among nestlings of this species.

  8. Biological and phylogenetic characteristics of West African lineages of West Nile virus

    PubMed Central

    Faye, Martin; Dia, Moussa; Freire, Caio César de Melo; Loucoubar, Cheikh; Zanotto, Paolo Marinho de Andrade; Faye, Ousmane; Sall, Amadou Alpha

    2017-01-01

    The West Nile virus (WNV), isolated in 1937, is an arbovirus (arthropod-borne virus) that infects thousands of people each year. Despite its burden on global health, little is known about the virus’ biological and evolutionary dynamics. As several lineages are endemic in West Africa, we obtained the complete polyprotein sequence from three isolates from the early 1990s, each representing a different lineage. We then investigated differences in growth behavior and pathogenicity for four distinct West African lineages in arthropod (Ap61) and primate (Vero) cell lines, and in mice. We found that genetic differences, as well as viral-host interactions, could play a role in the biological properties in different WNV isolates in vitro, such as: (i) genome replication, (ii) protein translation, (iii) particle release, and (iv) virulence. Our findings demonstrate the endemic diversity of West African WNV strains and support future investigations into (i) the nature of WNV emergence, (ii) neurological tropism, and (iii) host adaptation. PMID:29117195

  9. Examination of West Nile Virus Neuroinvasion and Neuropathogenesis in the Central Nervous System of a Murine Model.

    PubMed

    Sultana, Hameeda

    2016-01-01

    West Nile virus (WNV) is a neurotropic virus that causes inflammation and neuronal loss in the Central Nervous System leading to encephalitis and death. In this chapter, detailed methods to detect WNV in the murine brain tissue by quantitative real-time polymerase chain reaction and viral plaque assays are described. Determination of WNV neuropathogenesis by Hematoxylin and Eosin staining and immunohistochemical procedures are provided. In addition, TUNEL assays to determine neuronal loss during WNV neuropathogenesis are discussed in detail. Collectively, the methods mentioned in this chapter provide an overview to understand neuroinvasion and neuropathogenesis in a murine model of WNV infection.

  10. An outbreak of West Nile Virus infection in the region of Monastir, Tunisia, 2003

    PubMed Central

    Riabi, Samira; Gaaloul, Imed; Mastouri, Maha; Hassine, Mohsen; Aouni, Mahjoub

    2014-01-01

    Background A West Nile (WN) fever epidemic occurred in the region of Monastir, Tunisia, between August and October 2003. Aim of the study We attempt to describe the epidemiology, clinical presentation, and outcome of patients with confirmed West Nile virus (WNV) infection. Methods Three groups of specimens were prepared. One was made up of serum only (n  =  43), the other of cerebrospinal fluid (CSF) only (n  =  30), and the third group was made up of both (n  =  40). These specimens were obtained from 113 patients. A serological diagnosis and evidence of WNV genome by nested reverse-transcriptase polymerase chain reaction (nRT-PCR) and TaqMan reverse transcription-polymerase chain reaction (RT-PCR) were carried out. Results Thirty-eight cases (33.6%) were serologically positive. Results of nRT-PCR showed a total of 10 positive cases of WNV (8.8%) detected in group 1 (n  =  1/43), group 2 (n  =  5/30), and group 3 (n  =  4/40) whereas the PCR TaqMan showed 18 positive samples (15.9%) found in group 1 (n  =  3/43), group 2 (n  =  9/30), and group 3 (n  =  6/40). All TaqMan PCR positive cases were nRT-PCR positive. In addition, four serologically probable cases were confirmed by TaqMan PCR. The attempts to isolate WNV by cell culture were unsuccessful. Considering the results of TaqMan assay and the serological diagnosis, WNV infection was confirmed in a total of 42 patients. The main clinical presentations were meningoencephalitis (40%), febrile disease (95%), and meningitis (36%). Eight patients (19%) died. The highest case-fatality rates occurred among patients aged ≧55 years. The phylogenetic analysis revealed that isolates of WNV were closely related to the Tunisian strain 1997 (PAH001) and the Israeli one (Is-98). Conclusions West Nile virus is a reemerging global pathogen that remains an important public health challenge in the next decade. PMID:24766339

  11. Factors That Influence the Transmission of West Nile Virus in Florida.

    PubMed

    Day, Jonathan F; Tabachnick, Walter J; Smartt, Chelsea T

    2015-09-01

    West Nile virus (WNV) was first detected in North America in New York City during the late summer of 1999 and was first detected in Florida in 2001. Although WNV has been responsible for widespread and extensive epidemics in human populations and epizootics in domestic animals and wildlife throughout North America, comparable epidemics have never materialized in Florida. Here, we review some of the reasons why WNV has yet to cause an extensive outbreak in Florida. The primary vector of mosquito-borne encephalitis virus in Florida is Culex nigripalpus Theobald. Rainfall, drought, and temperature are the primary factors that regulate annual populations of this species. Cx. nigripalpus is a competent vector of WNV, St. Louis encephalitis virus, and eastern equine encephalitis virus in Florida, and populations of this species can support focal amplification and transmission of these arboviruses. We propose that a combination of environmental factors influencing Cx. nigripalpus oviposition, blood-feeding behavior, and vector competence have limited WNV transmission in Florida to relatively small focal outbreaks and kept the state free of a major epidemic. Florida must remain vigilant to the danger from WNV, because a change in these environmental factors could easily result in a substantial WNV epidemic rivaling those seen elsewhere in the United States. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Comparison of immune responses of brown-headed cowbird and related blackbirds to west Nile and other mosquito-borne encephalitis viruses.

    PubMed

    Reisen, William K; Hahn, D Caldwell

    2007-07-01

    The rapid geographic spread of West Nile virus (family Flaviviridae, genus Flavivirus, WNV) across the United States has stimulated interest in comparative host infection studies to delineate competent avian hosts critical for viral amplification. We compared the host competence of four taxonomically related blackbird species (Icteridae) after experimental infection with WNV and with two endemic, mosquito-borne encephalitis viruses, western equine encephalomyelitis virus (family Togaviridae, genus Alphavirus, WEEV), and St. Louis encephalitis virus (family Flaviviridae, genus Flavivirus, SLEV). We predicted differences in disease resistance among the blackbird species based on differences in life history, because they differ in geographic range and life history traits that include mating and breeding systems. Differences were observed among the response of these hosts to all three viruses. Red-winged Blackbirds were more susceptible to SLEV than Brewer's Blackbirds, whereas Brewer's Blackbirds were more susceptible to WEEV than Red-winged Blackbirds. In response to WNV infection, cowbirds showed the lowest mean viremias, cleared their infections faster, and showed lower antibody levels than concurrently infected species. Brown-headed Cowbirds also exhibited significantly lower viremia responses after infection with SLEV and WEEV as well as coinfection with WEEV and WNV than concurrently infected icterids. We concluded that cowbirds may be more resistant to infection to both native and introduced viruses because they experience heightened exposure to a variety of pathogens of parenting birds during the course of their parasitic life style.

  13. Comparison of immune responses of brown-headed cowbird and related blackbirds to West Nile and other mosquito-borne encephalitis viruses

    USGS Publications Warehouse

    Reisen, W.K.; Hahn, D.C.

    2007-01-01

    The rapid geographic spread of West Nile virus (family Flaviviridae, genus Flavivirus, WNV) across the United States has stimulated interest in comparative host infection studies to delineate competent avian hosts critical for viral amplification. We compared the host competence of four taxonomically related blackbird species (Icteridae) after experimental infection with WNV and with two endemic, mosquito-borne encephalitis viruses, western equine encephalomyelitis virus (family Togaviridae, genus Alphavirus, WEEV), and St, Louis encephalitis virus (family Flaviviridae, genus Flavivirus, SLEV). We predicted differences in disease resistance among the blackbird species based on differences in life history, because they differ in geographic range and life history traits that include mating and breeding systems. Differences were observed among the response of these hosts to all three viruses, Red-winged Blackbirds were more susceptible to SLEV than Brewer's Blackbirds, whereas Brewer's Blackbirds were more susceptible to WEEV than Red-winged Blackbirds. In response to WNV infection, cowbirds showed the lowest mean viremias, cleared their infections faster, and showed lower antibody levels than concurrently infected species. Brown-headed Cowbirds also exhibited significantly lower viremia responses after infection with SLEV and WEEV as well as coinfection with WEEV and WNV than concurrently infected icterids. We concluded that cowbirds may be more resistant to infection to both native and introduced viruses because they experience heightened exposure to a variety of pathogens of parenting birds during the course of their parasitic life style.

  14. Fluid Spatial Dynamics of West Nile Virus in the United States: Rapid Spread in a Permissive Host Environment.

    PubMed

    Di Giallonardo, Francesca; Geoghegan, Jemma L; Docherty, Douglas E; McLean, Robert G; Zody, Michael C; Qu, James; Yang, Xiao; Birren, Bruce W; Malboeuf, Christine M; Newman, Ruchi M; Ip, Hon S; Holmes, Edward C

    2016-01-15

    The introduction of West Nile virus (WNV) into North America in 1999 is a classic example of viral emergence in a new environment, with its subsequent dispersion across the continent having a major impact on local bird populations. Despite the importance of this epizootic, the pattern, dynamics, and determinants of WNV spread in its natural hosts remain uncertain. In particular, it is unclear whether the virus encountered major barriers to transmission, or spread in an unconstrained manner, and if specific viral lineages were favored over others indicative of intrinsic differences in fitness. To address these key questions in WNV evolution and ecology, we sequenced the complete genomes of approximately 300 avian isolates sampled across the United States between 2001 and 2012. Phylogenetic analysis revealed a relatively star-like tree structure, indicative of explosive viral spread in the United States, although with some replacement of viral genotypes through time. These data are striking in that viral sequences exhibit relatively limited clustering according to geographic region, particularly for those viruses sampled from birds, and no strong phylogenetic association with well-sampled avian species. The genome sequence data analyzed here also contain relatively little evidence for adaptive evolution, particularly of structural proteins, suggesting that most viral lineages are of similar fitness and that WNV is well adapted to the ecology of mosquito vectors and diverse avian hosts in the United States. In sum, the molecular evolution of WNV in North America depicts a largely unfettered expansion within a permissive host and geographic population with little evidence of major adaptive barriers. How viruses spread in new host and geographic environments is central to understanding the emergence and evolution of novel infectious diseases and for predicting their likely impact. The emergence of the vector-borne West Nile virus (WNV) in North America in 1999

  15. Field Methods and Sample Collection Techniques for the Surveillance of West Nile Virus in Avian Hosts.

    PubMed

    Wheeler, Sarah S; Boyce, Walter M; Reisen, William K

    2016-01-01

    Avian hosts play an important role in the spread, maintenance, and amplification of West Nile virus (WNV). Avian susceptibility to WNV varies from species to species thus surveillance efforts can focus both on birds that survive infection and those that succumb. Here we describe methods for the collection and sampling of live birds for WNV antibodies or viremia, and methods for the sampling of dead birds. Target species and study design considerations are discussed.

  16. Immunodominance and Functional Activities of Antibody Responses to Inactivated West Nile Virus and Recombinant Subunit Vaccines in Mice▿

    PubMed Central

    Zlatkovic, Juergen; Stiasny, Karin; Heinz, Franz X.

    2011-01-01

    Factors controlling the dominance of antibody responses to specific sites in viruses and/or protein antigens are ill defined but can be of great importance for the induction of potent immune responses to vaccines. West Nile virus and other related important human-pathogenic flaviviruses display the major target of neutralizing antibodies, the E protein, in an icosahedral shell at the virion surface. Potent neutralizing antibodies were shown to react with the upper surface of domain III (DIII) of this protein. Using the West Nile virus system, we conducted a study on the immunodominance and functional quality of E-specific antibody responses after immunization of mice with soluble protein E (sE) and isolated DIII in comparison to those after immunization with inactivated whole virions. With both virion and sE, the neutralizing response was dominated by DIII-specific antibodies, but the functionality of these antibodies was almost four times higher after virion immunization. Antibodies induced by the isolated DIII had an at least 15-fold lower specific neutralizing activity than those induced by the virion, and only 50% of these antibodies were able to bind to virus particles. Our results suggest that immunization with the tightly packed E in virions focuses the DIII antibody response to the externally exposed sites of this domain which are the primary targets for virus neutralization, different from sE and isolated DIII, which also display protein surfaces that are cryptic in the virion. Despite its low potency for priming, DIII was an excellent boosting antigen, suggesting novel vaccination strategies that strengthen and focus the antibody response to critical neutralizing sites in DIII. PMID:21147919

  17. Chimeric vaccine composed of viral peptide and mammalian heat-shock protein 60 peptide protects against West Nile virus challenge

    PubMed Central

    Gershoni-Yahalom, Orly; Landes, Shimon; Kleiman-Shoval, Smadar; Ben-Nathan, David; Kam, Michal; Lachmi, Bat-El; Khinich, Yevgeny; Simanov, Michael; Samina, Itzhak; Eitan, Anat; Cohen, Irun R; Rager-Zisman, Bracha; Porgador, Angel

    2010-01-01

    The protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public-health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B-cell epitope from domain III of the WNV envelope protein, termed Ep15. To test whether this epitope can protect against WNV infection, we synthesized a linear chimeric peptide composed of Ep15 and the heat-shock protein 60 peptide, p458. The p458 peptide is an effective carrier peptide for subunit vaccines against other infectious agents. We now report that mice immunized with the chimeric peptide, p458-Ep15, were resistant to lethal challenges with three different WNV strains. Moreover, their brains were free of viral genome and infectious virus. Mice immunized with Ep15 alone or with p431-Ep15, a control conjugate, were not protected. The chimeric p458-Ep15 peptide induced WNV-specific immunoglobulin G antibodies that neutralized the virus and induced the secretion of interferon-γin vitro. Challenge of chimeric peptide-immunized mice considerably enhanced WNV-specific neutralizing antibodies. We conclude that this chimeric peptide can be used for formulation of a human vaccine against WNV. PMID:20331473

  18. Chimeric vaccine composed of viral peptide and mammalian heat-shock protein 60 peptide protects against West Nile virus challenge.

    PubMed

    Gershoni-Yahalom, Orly; Landes, Shimon; Kleiman-Shoval, Smadar; Ben-Nathan, David; Kam, Michal; Lachmi, Bat-El; Khinich, Yevgeny; Simanov, Michael; Samina, Itzhak; Eitan, Anat; Cohen, Irun R; Rager-Zisman, Bracha; Porgador, Angel

    2010-08-01

    The protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public-health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B-cell epitope from domain III of the WNV envelope protein, termed Ep15. To test whether this epitope can protect against WNV infection, we synthesized a linear chimeric peptide composed of Ep15 and the heat-shock protein 60 peptide, p458. The p458 peptide is an effective carrier peptide for subunit vaccines against other infectious agents. We now report that mice immunized with the chimeric peptide, p458-Ep15, were resistant to lethal challenges with three different WNV strains. Moreover, their brains were free of viral genome and infectious virus. Mice immunized with Ep15 alone or with p431-Ep15, a control conjugate, were not protected. The chimeric p458-Ep15 peptide induced WNV-specific immunoglobulin G antibodies that neutralized the virus and induced the secretion of interferon-gammain vitro. Challenge of chimeric peptide-immunized mice considerably enhanced WNV-specific neutralizing antibodies. We conclude that this chimeric peptide can be used for formulation of a human vaccine against WNV.

  19. Noncoding Subgenomic Flavivirus RNA Is Processed by the Mosquito RNA Interference Machinery and Determines West Nile Virus Transmission by Culex pipiens Mosquitoes.

    PubMed

    Göertz, G P; Fros, J J; Miesen, P; Vogels, C B F; van der Bent, M L; Geertsema, C; Koenraadt, C J M; van Rij, R P; van Oers, M M; Pijlman, G P

    2016-11-15

    Flaviviruses, such as Zika virus, yellow fever virus, dengue virus, and West Nile virus (WNV), are a serious concern for human health. Flaviviruses produce an abundant noncoding subgenomic flavivirus RNA (sfRNA) in infected cells. sfRNA results from stalling of the host 5'-3' exoribonuclease XRN1/Pacman on conserved RNA structures in the 3' untranslated region (UTR) of the viral genomic RNA. sfRNA production is conserved in insect-specific, mosquito-borne, and tick-borne flaviviruses and flaviviruses with no known vector, suggesting a pivotal role for sfRNA in the flavivirus life cycle. Here, we investigated the function of sfRNA during WNV infection of Culex pipiens mosquitoes and evaluated its role in determining vector competence. An sfRNA1-deficient WNV was generated that displayed growth kinetics similar to those of wild-type WNV in both RNA interference (RNAi)-competent and -compromised mosquito cell lines. Small-RNA deep sequencing of WNV-infected mosquitoes indicated an active small interfering RNA (siRNA)-based antiviral response for both the wild-type and sfRNA1-deficient viruses. Additionally, we provide the first evidence that sfRNA is an RNAi substrate in vivo Two reproducible small-RNA hot spots within the 3' UTR/sfRNA of the wild-type virus mapped to RNA stem-loops SL-III and 3' SL, which stick out of the three-dimensional (3D) sfRNA structure model. Importantly, we demonstrate that sfRNA-deficient WNV displays significantly decreased infection and transmission rates in vivo when administered via the blood meal. Finally, we show that transmission and infection rates are not affected by sfRNA after intrathoracic injection, thereby identifying sfRNA as a key driver to overcome the mosquito midgut infection barrier. This is the first report to describe a key biological function of sfRNA for flavivirus infection of the arthropod vector, providing an explanation for the strict conservation of sfRNA production. Understanding the flavivirus transmission

  20. Noncoding Subgenomic Flavivirus RNA Is Processed by the Mosquito RNA Interference Machinery and Determines West Nile Virus Transmission by Culex pipiens Mosquitoes

    PubMed Central

    Göertz, G. P.; Fros, J. J.; Miesen, P.; Vogels, C. B. F.; van der Bent, M. L.; Geertsema, C.; Koenraadt, C. J. M.; van Oers, M. M.

    2016-01-01

    ABSTRACT Flaviviruses, such as Zika virus, yellow fever virus, dengue virus, and West Nile virus (WNV), are a serious concern for human health. Flaviviruses produce an abundant noncoding subgenomic flavivirus RNA (sfRNA) in infected cells. sfRNA results from stalling of the host 5′-3′ exoribonuclease XRN1/Pacman on conserved RNA structures in the 3′ untranslated region (UTR) of the viral genomic RNA. sfRNA production is conserved in insect-specific, mosquito-borne, and tick-borne flaviviruses and flaviviruses with no known vector, suggesting a pivotal role for sfRNA in the flavivirus life cycle. Here, we investigated the function of sfRNA during WNV infection of Culex pipiens mosquitoes and evaluated its role in determining vector competence. An sfRNA1-deficient WNV was generated that displayed growth kinetics similar to those of wild-type WNV in both RNA interference (RNAi)-competent and -compromised mosquito cell lines. Small-RNA deep sequencing of WNV-infected mosquitoes indicated an active small interfering RNA (siRNA)-based antiviral response for both the wild-type and sfRNA1-deficient viruses. Additionally, we provide the first evidence that sfRNA is an RNAi substrate in vivo. Two reproducible small-RNA hot spots within the 3′ UTR/sfRNA of the wild-type virus mapped to RNA stem-loops SL-III and 3′ SL, which stick out of the three-dimensional (3D) sfRNA structure model. Importantly, we demonstrate that sfRNA-deficient WNV displays significantly decreased infection and transmission rates in vivo when administered via the blood meal. Finally, we show that transmission and infection rates are not affected by sfRNA after intrathoracic injection, thereby identifying sfRNA as a key driver to overcome the mosquito midgut infection barrier. This is the first report to describe a key biological function of sfRNA for flavivirus infection of the arthropod vector, providing an explanation for the strict conservation of sfRNA production. IMPORTANCE Understanding

  1. West Nile Virus lineage-2 in Culex specimens from Iran.

    PubMed

    Shahhosseini, Nariman; Chinikar, Sadegh; Moosa-Kazemi, Seyed Hassan; Sedaghat, Mohammad Mehdi; Kayedi, Mohammad Hassan; Lühken, Renke; Schmidt-Chanasit, Jonas

    2017-10-01

    Screening of mosquitoes for viruses is an important forecasting tool for emerging and re-emerging arboviruses. Iran has been known to harbour medically important arboviruses such as West Nile virus (WNV) and dengue virus (DENV) based on seroepidemiological data. However, there are no data about the potential mosquito vectors for arboviruses in Iran. This study was performed to provide mosquito and arbovirus data from Iran. A total of 32 317 mosquitos were collected at 16 sites in five provinces of Iran in 2015 and 2016. RT-PCR for detection of flaviviruses was performed. The PCR amplicons were sequenced, and 109 WNV sequences, including one obtained in this study, were used for phylogenetic analyses. The 32 317 mosquito specimens belonging to 25 species were morphologically distinguished and distributed into 1222 pools. Culex pipiens s.l. comprised 56.429%. One mosquito pool (0.08%), containing 46 unfed Cx. pipiens pipiens form pipiens (Cpp) captured in August 2015, was positive for flavivirus RNA. Subsequent sequencing and phylogenetic analyses revealed that the detected Iranian WNV strain belongs to lineage 2 and clusters with a strain recently detected in humans. No flaviviruses other than WNV were detected in the mosquito pools. Cpp could be a vector for WNV in Iran. Our findings indicate recent circulation of WNV lineage-2 strain in Iran and provide a solid base for more targeted arbovirus surveillance programs. © 2017 John Wiley & Sons Ltd.

  2. Genetic Variability of West Nile Virus in U.S. Blood Donors from the 2012 Epidemic Season

    DOE PAGES

    Grinev, Andriyan; Chancey, Caren; Volkova, Evgeniya; ...

    2016-05-16

    West Nile virus (WNV) is an arbovirus maintained in nature in a bird-mosquito enzootic cycle which can also infect other vertebrates including humans. WNV is now endemic in the United States (U.S.), causing yearly outbreaks that have resulted in an estimated total of 4–5 million human infections. Over 41,700 cases of West Nile disease, including 18,810 neuroinvasive cases and 1,765 deaths, were reported to the CDC between 1999 and 2014. In 2012, the second largest West Nile outbreak in the U.S. was reported, which caused 5,674 cases and 286 deaths. WNV continues to evolve, and three major WNV lineage Imore » genotypes (NY99, WN02, and SW/WN03) have been described in the U.S. since introduction of the virus in 1999. We report here the WNV sequences obtained from 19 human samples acquired during the 2012 U.S. outbreak and our examination of the evolutionary dynamics in WNV isolates sequenced from 1999–2012. Maximum-likelihood and Bayesian methods were used to perform the phylogenetic analyses. Selection pressure analyses were performed with the HyPhy package using the Datamonkey web-server. Using different codon-based and branch-site selection models, we detected a number of codons subjected to positive pressure in WNV genes. Thirteen of the 19 completely sequenced isolates from 10 U.S. states were genetically similar, sharing up to 55 nucleotide mutations and 4 amino acid substitutions when compared with the prototype isolate WN-NY99. Altogether, these analyses showed that following a brief contraction in 2008–2009, WNV genetic divergence in the U.S. continued to increase in 2012, and that closely related variants were found across a broad geographic range of the U.S., coincident with the second-largest WNV outbreak in U.S. history.« less

  3. Genetic Variability of West Nile Virus in U.S. Blood Donors from the 2012 Epidemic Season

    PubMed Central

    Grinev, Andriyan; Chancey, Caren; Volkova, Evgeniya; Añez, Germán; Heisey, Daniel A. R.; Winkelman, Valerie; Foster, Gregory A.; Williamson, Phillip; Stramer, Susan L.; Rios, Maria

    2016-01-01

    West Nile virus (WNV) is an arbovirus maintained in nature in a bird-mosquito enzootic cycle which can also infect other vertebrates including humans. WNV is now endemic in the United States (U.S.), causing yearly outbreaks that have resulted in an estimated total of 4–5 million human infections. Over 41,700 cases of West Nile disease, including 18,810 neuroinvasive cases and 1,765 deaths, were reported to the CDC between 1999 and 2014. In 2012, the second largest West Nile outbreak in the U.S. was reported, which caused 5,674 cases and 286 deaths. WNV continues to evolve, and three major WNV lineage I genotypes (NY99, WN02, and SW/WN03) have been described in the U.S. since introduction of the virus in 1999. We report here the WNV sequences obtained from 19 human samples acquired during the 2012 U.S. outbreak and our examination of the evolutionary dynamics in WNV isolates sequenced from 1999–2012. Maximum-likelihood and Bayesian methods were used to perform the phylogenetic analyses. Selection pressure analyses were performed with the HyPhy package using the Datamonkey web-server. Using different codon-based and branch-site selection models, we detected a number of codons subjected to positive pressure in WNV genes. Thirteen of the 19 completely sequenced isolates from 10 U.S. states were genetically similar, sharing up to 55 nucleotide mutations and 4 amino acid substitutions when compared with the prototype isolate WN-NY99. Overall, these analyses showed that following a brief contraction in 2008–2009, WNV genetic divergence in the U.S. continued to increase in 2012, and that closely related variants were found across a broad geographic range of the U.S., coincident with the second-largest WNV outbreak in U.S. history. PMID:27182734

  4. West Nile virus in Spain: report of the first diagnosed case (in Spain) in a human with aseptic meningitis.

    PubMed

    Kaptoul, Diana; Viladrich, Pedro F; Domingo, Cristina; Niubó, Jordi; Martínez-Yélamos, Sergio; De Ory, Fernando; Tenorio, Antonio

    2007-01-01

    We report the first case of illness caused by West Nile virus (WNV) so far diagnosed in Spain. A 21-y-old male presented with clinical and biological signs compatible with viral meningitis. Acute and convalescent serum samples showed IgM and IgG positivity for WNV. These results were confirmed by microneutralization assays.

  5. The Interferon-Stimulated Gene Ifitm3 Restricts West Nile Virus Infection and Pathogenesis.

    PubMed

    Gorman, Matthew J; Poddar, Subhajit; Farzan, Michael; Diamond, Michael S

    2016-09-15

    The interferon-induced transmembrane protein (IFITM) family of proteins inhibit infection of several different enveloped viruses in cell culture by virtue of their ability to restrict entry and fusion from late endosomes. As few studies have evaluated the importance of Ifitm3 in vivo in restricting viral pathogenesis, we investigated its significance as an antiviral gene against West Nile virus (WNV), an encephalitic flavivirus, in cells and mice. Ifitm3(-/-) mice were more vulnerable to lethal WNV infection, and this was associated with greater virus accumulation in peripheral organs and central nervous system tissues. As no difference in viral burden in the brain or spinal cord was observed after direct intracranial inoculation, Ifitm3 likely functions as an antiviral protein in nonneuronal cells. Consistent with this, Ifitm3(-/-) fibroblasts but not dendritic cells resulted in higher yields of WNV in multistep growth analyses. Moreover, transcomplementation experiments showed that Ifitm3 inhibited WNV infection independently of Ifitm1, Ifitm2, Ifitm5, and Ifitm6. Beyond a direct effect on viral infection in cells, analysis of the immune response in WNV-infected Ifitm3(-/-) mice showed decreases in the total number of B cells, CD4(+) T cells, and antigen-specific CD8(+) T cells. Finally, bone marrow chimera experiments demonstrated that Ifitm3 functioned in both radioresistant and radiosensitive cells, as higher levels of WNV were observed in the brain only when Ifitm3 was absent from both compartments. Our analyses suggest that Ifitm3 restricts WNV pathogenesis likely through multiple mechanisms, including the direct control of infection in subsets of cells. As part of the mammalian host response to viral infections, hundreds of interferon-stimulated genes (ISGs) are induced. The inhibitory activity of individual ISGs varies depending on the specific cell type and viral pathogen. Among ISGs, the genes encoding interferon-induced transmembrane protein (IFITM

  6. An examination of the effect of aerosolized permanone insecticide on zebra finch susceptibility to West Nile virus

    USGS Publications Warehouse

    Jankowski, Mark D.; Murray, E. Moore; Hofmeister, Erik K.

    2017-01-01

    West Nile virus is primarily maintained cryptically primarily in avian (Passerine) populations where it is transmitted by Culex spp. mosquitoes. Mosquito control measures currently include physical activities to reduce mosquito breeding sites, the application of mosquito larvicides, or aerosolized insecticides to kill adults (adulticides) when arboviral diseases such as West Nile virus (WNV) or Zika virus are detected in mosquito populations. Organochlorine, organohosphorus, carbamate and pyrethroid insecticides are often used. Previous work suggests an effect of pyrethroids on the immune system in a variety of vertebrates. We examined the effects of exposure to aerosolized Permanone® 30:30 insecticide (permethrin and piperonyl butoxide in soy oil vehicle) at ∼103−106x potential environmental concentrations on the response of captive zebra finches (Taeniopygia guttata) to experimental challenge with WNV. Compared to vehicle control birds, WNV outcome was unchanged (65% of birds produced a viremia) in the ‘low’ exposure (9.52 mg/m3±3.13 SD permethrin) group, but reduced in the ‘high’ exposure (mean 376.5 mg/m3±27.9 SD permethrin) group (30% were viremic) (p < 0.05). After clearing WNV infection, birds treated with Permanone regained less body mass than vehicle treated birds (p < 0.001). Our study suggests that exposure to aerosolized Permanone insecticide at levels exceeding typical application rates has the potential to not change or mildly enhance a bird's resistance to WNV.

  7. Spatial and Temporal Distribution of West Nile Virus in Horses in Israel (1997–2013) - from Endemic to Epidemics

    PubMed Central

    Aharonson-Raz, Karin; Lichter-Peled, Anat; Tal, Shlomit; Gelman, Boris; Cohen, Daniel; Klement, Eyal; Steinman, Amir

    2014-01-01

    With the rapid global spread of West Nile virus (WNV) and the endemic state it has acquired in new geographical areas, we hereby bring a thorough serological investigation of WNV in horses in a longstanding endemic region, such as Israel. This study evaluates the environmental and demographic risk factors for WNV infection in horses and suggests possible factors associated with the transition from endemic to epidemic state. West Nile virus seroprevalence in horses in Israel was determined throughout a period of more than a decade, before (1997) and after (2002 and 2013) the massive West Nile fever outbreak in humans and horses in 2000. An increase in seroprevalence was observed, from 39% (113/290) in 1997 to 66.1% (547/827) in 2002 and 85.5% (153/179) in 2013, with persistent significantly higher seroprevalence in horses situated along the Great Rift Valley (GRV) area, the major birds' migration route in Israel. Demographic risk factors included age and breed of the horse. Significantly lower spring precipitation was observed during years with increased human incidence rate that occurred between 1997–2007. Hence, we suggest referring to Israel as two WNV distinct epidemiological regions; an endemic region along the birds' migration route (GRV) and the rest of the country which perhaps suffers from cyclic epidemics. In addition, weather conditions, such as periods of spring drought, might be associated with the transition from endemic state to epidemic state of WNV. PMID:25402217

  8. Transmission dynamics and changing epidemiology of West Nile virus.

    PubMed

    Blitvich, Bradley J

    2008-06-01

    West Nile virus (WNV) is a flavivirus that is maintained in a bird-mosquito transmission cycle. Humans, horses and other non-avian vertebrates are usually incidental hosts, but evidence is accumulating that this might not always be the case. Historically, WNV has been associated with asymptomatic infections and sporadic disease outbreaks in humans and horses in Africa, Europe, Asia and Australia. However, since 1994, the virus has caused frequent outbreaks of severe neuroinvasive disease in humans and horses in Europe and the Mediterranean Basin. In 1999, WNV underwent a dramatic expansion of its geographic range, and was reported for the first time in the Western Hemisphere during an outbreak of human and equine encephalitis in New York City. The outbreak was accompanied by extensive and unprecedented avian mortality. Since then, WNV has dispersed across the Western Hemisphere and is now found throughout the USA, Canada, Mexico and the Caribbean, and parts of Central and South America. WNV has been responsible for >27,000 human cases, >25,000 equine cases and hundreds of thousands of avian deaths in the USA but, surprisingly, there have been only sparse reports of WNV disease in vertebrates in the Caribbean and Latin America. This review summarizes our current understanding of WNV with particular emphasis on its transmission dynamics and changing epidemiology.

  9. Seroprevalence of West Nile Virus in feral horses on Sheldon National Wildlife Refuge, Nevada, United States

    USGS Publications Warehouse

    Franson, J. Christian; Hofmeister, Erik K.; Collins, Gail H.; Dusek, Robert J.

    2011-01-01

    We screened 1,397 feral horses (Equus caballus) on Sheldon National Wildlife Refuge, Nevada, United States, for IgM and IgG against flavivirus during 2004–2006, 2008, and 2009. Positive serum samples were tested for neutralizing antibodies to West Nile virus (WNV) and St. Louis encephalitis virus (SLEV). One animal was positive for antibody against WNV in 2004, but all others tested in 2004–2006 were negative. In 2008 and 2009, we found evidence of increasing seropositive horses with age, whereas seroprevalence of WNV decreased from 19% in 2008 to 7.2% in 2009. No horses were positive for antibody against SLEV. Being unvaccinated, feral horses can be useful for WNV surveillance.

  10. Culex pipiens, an Experimental Efficient Vector of West Nile and Rift Valley Fever Viruses in the Maghreb Region

    PubMed Central

    Amraoui, Fadila; Krida, Ghazi; Bouattour, Ali; Rhim, Adel; Daaboub, Jabeur; Harrat, Zoubir; Boubidi, Said-Chawki; Tijane, Mhamed; Sarih, Mhammed; Failloux, Anna-Bella

    2012-01-01

    West Nile fever (WNF) and Rift Valley fever (RVF) are emerging diseases causing epidemics outside their natural range of distribution. West Nile virus (WNV) circulates widely and harmlessly in the old world among birds as amplifying hosts, and horses and humans as accidental dead-end hosts. Rift Valley fever virus (RVFV) re-emerges periodically in Africa causing massive outbreaks. In the Maghreb, eco-climatic and entomologic conditions are favourable for WNV and RVFV emergence. Both viruses are transmitted by mosquitoes belonging to the Culex pipiens complex. We evaluated the ability of different populations of Cx. pipiens from North Africa to transmit WNV and the avirulent RVFV Clone 13 strain. Mosquitoes collected in Algeria, Morocco, and Tunisia during the summer 2010 were experimentally infected with WNV and RVFV Clone 13 strain at titers of 107.8 and 108.5 plaque forming units/mL, respectively. Disseminated infection and transmission rates were estimated 14–21 days following the exposure to the infectious blood-meal. We show that 14 days after exposure to WNV, all mosquito st developed a high disseminated infection and were able to excrete infectious saliva. However, only 69.2% of mosquito strains developed a disseminated infection with RVFV Clone 13 strain, and among them, 77.8% were able to deliver virus through saliva. Thus, Cx. pipiens from the Maghreb are efficient experimental vectors to transmit WNV and to a lesser extent, RVFV Clone 13 strain. The epidemiologic importance of our findings should be considered in the light of other parameters related to mosquito ecology and biology. PMID:22693557

  11. Serosurveillance for Japanese encephalitis and West Nile viruses in resident birds in Hawai'i.

    PubMed

    Nemeth, Nicole M; Bosco-Lauth, Angela M; Sciulli, Rebecca H; Gose, Remedios B; Nagata, Mark T; Bowen, Richard A

    2010-04-01

    Japanese encephalitis virus (JEV) and West Nile virus (WNV) are emerging zoonotic arboviruses that have recently undergone intercontinental expansion. Both JEV and WNV are naturally transmitted between mosquito vectors and vertebrate reservoir hosts, including birds. A potential route of JEV introduction from Asia to western North America is via the Hawaiian archipelago, while the spread of WNV from mainland North America to Hawai'i is also considered an impending threat. We surveyed resident, non-native bird sera for antibodies to JEV and WNV on two Hawaiian Islands from 2004-2005. Three of 1,835 birds (0.16%) had evidence of antiflavivirus antibodies, demonstrating neutralizing activity to JEV and St. Louis encephalitis virus (SLEV). These detections could represent a limited transmission focus of either, or both, JEV and SLEV, or cross-reactive antibodies due to primary infection with an alternate flavivirus. Frequent air traffic from both Asia and North America to Hawai'i, along with the presence of probable competent vectors and amplifying vertebrate hosts in Hawai'i, increases the likelihood of introduction and maintenance of novel flaviviruses. Therefore, it is important to monitor for the presence of these viruses.

  12. West Nile virus: the Italian national transplant network reaction to an alert in the north-eastern region, Italy 2011.

    PubMed

    Costa, A Nanni; Capobianchi, M R; Ippolito, G; Palù, G; Barzon, L; Piccolo, G; Andreetta, B; Filippetti, M; Fehily, D; Lombardini, L; Grossi, P

    2011-10-13

    We report four cases of West Nile virus (WNV) transmission following a single multiorgan donation in north-eastern Italy. The transmissions were promptly detected by local transplant centres. The donor had been tested for WNV by nucleic acid amplification test (NAT) prior to transplantation and was negative. There were no detected errors in the nationally implemented WNV safety protocols.

  13. Clinical evaluation and outcomes of naturally acquired West Nile virus infection in raptors.

    PubMed

    Nemeth, Nicole M; Kratz, Gail E; Bates, Rebecca; Scherpelz, Judy A; Bowen, Richard A; Komar, Nicholas

    2009-03-01

    West Nile virus (WNV) infection and associated disease and mortality have been documented in numerous North American raptor species. Information regarding clinical presentations and long-term outcomes of WNV-infected raptors is important in the clinic for the diagnosis, treatment, and assessment of prognosis, as well as for understanding potential population level effects on raptor species. Raptors of 22 species admitted to a rehabilitation clinic were tested, from 2002 to 2005, for previous and acute WNV infection, while comparing clinical syndromes, trauma, and rehabilitation outcomes. Forty-two percent of admitted raptors (132/314) had been infected with WNV, and these presented with a WNV-attributed clinical disease rate of 67.4% (89/132). West Nile virus-infected raptors were less likely to be released (79/132 [59.8%]) than negative raptors (138/182 [75.8%]) and more likely to die or be euthanized (47/132 [35.6%] for WNV-infected vs. 32/182 [17.6%] for WNV-negative). However, WNV-infected raptors with neurologic disease were no less likely to be released (29/53 [54.7%]) than those without neurologic disease (50/79 [63.3%]). Clinical WNV-associated syndromes varied among species. Great horned owls (Bubo virginianus) were more likely to have neurologic signs, whereas American kestrels (Falco sparverius) and Swainson's hawks (Buteo swainsonii) were less likely to have neurologic signs. These results suggest that free-ranging raptors are frequently infected with WNV and that clinical syndromes differ among species. WNV has potentially devastating effects on raptors; however, rehabilitation of WNV-infected raptors can lead to positive outcomes, even for those having had severe neurologic disease.

  14. Surface-enhanced Raman scattering detection of DNA derived from the West Nile virus genome using magnetic capture of Raman-active gold nanoparticles

    USDA-ARS?s Scientific Manuscript database

    A model paramagnetic nanoparticle (MNP) assay is demonstrated for surface-enhanced Raman scattering (SERS) detection of DNA oligonucleotides derived from the West Nile virus (WNV) genome. Detection is based on the capture of WNV target sequences by hybridization with complementary oligonucleotide pr...

  15. Equine Immunoglobulin and Equine Neutralizing F(ab')₂ Protect Mice from West Nile Virus Infection.

    PubMed

    Cui, Jiannan; Zhao, Yongkun; Wang, Hualei; Qiu, Boning; Cao, Zengguo; Li, Qian; Zhang, Yanbo; Yan, Feihu; Jin, Hongli; Wang, Tiecheng; Sun, Weiyang; Feng, Na; Gao, Yuwei; Sun, Jing; Wang, Yanqun; Perlman, Stanley; Zhao, Jincun; Yang, Songtao; Xia, Xianzhu

    2016-12-18

    West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab')₂ fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab')₂ fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab')₂ passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV.

  16. Cross-protection between West Nile and Japanese encephalitis viruses in red-winged blackbirds (Agelaius phoeniceus).

    PubMed

    Nemeth, Nicole M; Bosco-Lauth, Angela M; Bowen, Richard A

    2009-09-01

    Similar to West Nile virus (WNV), Japanese encephalitis virus (JEV) has a history of intercontinental spread, and birds are important for the maintenance and transmission of both of these closely related viruses. We examined viremic and serologic responses of blackbirds (Agelaius phoeniceus), with and without immunity to WNV, following experimental inoculation with two strains of JEV. Japanese encephalitis (JE) viremia was detected in only one of 16 (6.3%) WNV-immune birds, while all 16 nonimmune birds had detectable JE viremia. Two weeks after JEV inoculation, all birds without pre-existing WNV immunity had clearly distinguishable anti-JEV antibodies, while in all birds with pre-existing WNV immunity, antibodies to WNV and JEV were either indistinguishable or the anti-WNV antibody titers were significantly higher. As WNV is endemic throughout much of North America, WNV immunity among birds may dampen transmission while complicating the serologic diagnosis of JEV, should this pathogen be introduced to North America.

  17. West Nile encephalitis outbreak in Kerala, India, 2011.

    PubMed

    Anukumar, B; Sapkal, Gajanan N; Tandale, Babasheb V; Balasubramanian, R; Gangale, Daya

    2014-09-01

    An outbreak of acute encephalitis syndrome (AES) was reported in Kerala in India in May 2011. The outbreak features were unusual in terms of seasonality, geographical distribution, age group, and clinical manifestations in comparison to the epidemiological features of Japanese Encephalitis. To detect the etiology of the acute encephalitis syndrome outbreak. Investigation of outbreak was undertaken by collection of brief clinical history and epidemiological details along with the specimens for viral diagnosis. The serum/CSF samples (patients=208) received from the sentinel hospitals were subjected to IgM capture ELISA and RT-PCR specific for Japanese encephalitis (JE) virus and West Nile virus (WNV). The JE/WN IgM positive samples were further tested by serum neutralization assay for the presence of JE and WNV specific neutralizing antibody. Most of the affected patients were aged above 15 years. No spatial clustering of the disease was noticed. Cases were observed in premonsoon and early monsoon season and in JE non-endemic area of Kerala. A total of 47 patient samples were positive for in-house JE IgM capture ELISA and WNV IgM capture ELISA. Serum neutralization assay result revealed that 32 of 42 (76.19%) sera were positive for WNV neutralization antibodies. WNV was isolated from a clinical specimen. Phylogenetic analysis of WNV envelope gene revealed 99% homology with Russian Lineage 1 WNV. West Nile virus (WNV) etiology was confirmed by virus isolation and detection of virus specific antibody from clinical specimen. Phylogenetic analysis grouped the current strain in lineage I West Nile virus. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. West Nile Virus Lineage 2 Associated with Human Case in Republic of Serbia.

    PubMed

    Jovanović Galović, Aleksandra; Weyer, Jacqueline; Jansen van Vuren, Petrus; Paweska, Janusz T; Radovanov, Jelena; Kovačević, Gordana; Hrnjaković Cvjetković, Ivana; Petrović, Vladimir; Blumberg, Lucille H; Milošević, Vesna

    2017-11-01

    A suspicion on West Nile virus (WNV) in Serbia was first reported in 1972 by a seroprevalence study, after which no data were available for four decades. We report full sequence of the isolate obtained for the first time from a human sample in Serbia. The closest clustering was obtained with lineage 2 WNV identified in Greece in 2010. Since WNV lineage 2 emerged in Europe in 2004, a cocirculation of lineages 1 and 2-as observed in Hungary and Italy-cannot be excluded. The reinforcement of surveillance will be required to investigate the possible cocirculation of the two lineages and the burden of WNV in the local population.

  19. Fever of Unknown Origin in a Patient with Confirmed West Nile Virus Meningoencephalitis

    PubMed Central

    Sabre, Alexander; Farricielli, Laurie

    2014-01-01

    West Nile Virus (WNV), an RNA arbovirus and member of the Japanese encephalitis virus antigenic complex, causes a wide range of clinical symptoms, from asymptomatic to encephalitis and meningitis. Nearly all human infections of WNV are due to mosquito bites with birds being the primary amplifying hosts. Advanced age is the most important risk factor for neurological disease leading most often to poor prognosis in those afflicted. We report a case of WNV meningoencephalitis in a 93-year-old Caucasian male who presented with fever of unknown origin (FUO) and nuchal rigidity that rapidly decompensated within 24 h to a persistent altered mental state during inpatient stay. The patient's ELISA antibody titers confirmed pathogenesis of disease by WNV; he given supportive measures and advanced to an excellent recovery. In regard to the approach of FUO, it is important to remain impartial yet insightful to all elements when determining pathogenesis in atypical presentation. PMID:25580318

  20. Enhanced West Nile Virus Surveillance in a Dengue-Endemic Area—Puerto Rico, 2007

    PubMed Central

    Torres-Aponte, Jomil M.; Luce, Richard R.; Hunsperger, Elizabeth; Muñoz-Jordan, Jorge L.; Beltrán, Manuela; Vergne, Edgardo; Argüello, D. Fermín; García, Enid J.; Sun, Wellington; Tomashek, Kay M.

    2013-01-01

    In June of 2007, West Nile virus (WNV) was detected in sentinel chickens and blood donors in Puerto Rico, where dengue virus (DENV) is hyperendemic. Enhanced human surveillance for acute febrile illness (AFI) began in eastern Puerto Rico on July 1, 2007. Healthcare providers submitted specimens from AFI cases for WNV and DENV virology and serology testing. Over 6 months, 385 specimens were received from 282 cases; 115 (41%) specimens were DENV laboratory-positive, 86 (31%) specimens were laboratory-indeterminate, and 32 (11%) specimens were laboratory-negative for WNV and DENV. One WNV infection was detected by anti-WNV immunoglobulin M (IgM) antibody and confirmed by a plaque reduction neutralization test. DENV and WNV infections could not be differentiated in 27 cases (10%). During a period of active WNV transmission, enhanced human surveillance identified one case of symptomatic WNV infection. Improved diagnostic methods are needed to allow differentiation of WNV and DENV in dengue-endemic regions. PMID:23478583

  1. Detection of West Nile virus in wild birds in Tana River and Garissa Counties, Kenya.

    PubMed

    Nyamwaya, Doris; Wang'ondu, Virginia; Amimo, Joshua; Michuki, George; Ogugo, Moses; Ontiri, Enoch; Sang, Rosemary; Lindahl, Johanna; Grace, Delia; Bett, Bernard

    2016-11-23

    West Nile fever virus is a zoonotic arboviral infection maintained in a sylvatic cycle involving mosquito vectors and birds. It is one the arboviruses whose geographical range is expanding because of climate and land use changes that enhance the densities of mosquitoes and promote mosquito-bird-human interactions. We carried out a survey to determine the reservoirs of WNV among wild birds in Tana River and Garissa counties, Kenya. Blood samples were obtained from 361 randomly trapped wild birds. Using real-time polymerase chain reaction (PCR), all samples were screened for WNV using gene specific primer sets amplifying a portion of the E region of the genome encoding the envelope protein. Sixty five (65) out of 361 birds screened tested positive for WNV on real-time PCR assay. Sequencing of the selected positive samples reveals that the isolated WNV were most closely related to strains isolated from China (2011). A regression analysis indicated that sampling location influenced the occurrence of WNV while species, age, weight and sex of the birds did not have any effect. This study provides baseline information on the existing circulation of WNV in this region among wild bird reservoirs that could spill over to the human population and points to the need for implementation of surveillance programs to map the distribution of the virus among reservoirs. Awareness creation about West Nile fever in this region is important to improve its detection and management.

  2. Monitoring of West Nile virus, Usutu virus and Meaban virus in waterfowl used as decoys and wild raptors in southern Spain.

    PubMed

    Jurado-Tarifa, E; Napp, S; Lecollinet, S; Arenas, A; Beck, C; Cerdà-Cuéllar, M; Fernández-Morente, M; García-Bocanegra, I

    2016-12-01

    In the last decade, the number of emerging flaviviruses described worldwide has increased considerably, with wild birds acting as the main reservoir hosts of these viruses. We carried out an epidemiological survey to determine the seroprevalence of antigenically related flaviviruses, particularly West Nile virus (WNV), Usutu virus (USUV) and Meaban virus (MBV), in waterfowl used as decoys and wild raptors in Andalusia (southern Spain), the region considered to have the highest risk of flaviviruses circulation in Spain. The overall flaviviruses seroprevalence according to bELISA was 13.0% in both in decoys (n=1052) and wild raptors (n=123). Specific antibodies against WNV, USUV and MBV were confirmed by micro virus neutralization tests in 12, 38 and 4 of the seropositive decoys, respectively. This is the first study on WNV and USUV infections in decoys and the first report of MBV infections in waterfowl and raptors. Moreover we report the first description of WNV infections in short-toed snake eagle (Circaetus gallicus) and Montagu's harrier (Circus pygargus). The seropositivity obtained indicates widespread but not homogeneous distribution of WNV and USUV in Andalusia. The results also confirm endemic circulation of WNV, USUV and MBV in both decoys and wild raptors in southern Spain. Our results highlight the need to implement surveillance and control programs not only for WNV but also for other related flaviviruses. Further research is needed to determine the eco-epidemiological role that waterfowl and wild raptors play in the transmission of emerging flaviviruses, especially in decoys, given their close interactions with humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Role of Immune Aging in Susceptibility to West Nile Virus.

    PubMed

    Yao, Yi; Montgomery, Ruth R

    2016-01-01

    West Nile virus (WNV) can cause severe neuroinvasive disease in humans and currently no vaccine or specific treatments are available. As aging is the most prominent risk factor for WNV, age-related immune dysregulation likely plays an essential role in host susceptibility to infection with WNV. In this review, we summarize recent findings in effects of aging on immune responses to WNV infection. In particular, we focus on the age-dependent dysregulation of innate immune cell types-neutrophils, macrophages, and dendritic cells-in response to WNV infection, as well as age-related alterations in NK cells and γδ T cells that may associate with increased WNV susceptibility in older people. We also highlight two advanced technologies, i.e., mass cytometry and microRNA profiling, which significantly contribute to systems-level study of immune dysregulation in aging and should facilitate new discoveries for therapeutic intervention against WNV.

  4. Spreading and vanishing in a West Nile virus model with expanding fronts

    NASA Astrophysics Data System (ADS)

    Tarboush, Abdelrazig K.; Lin, ZhiGui; Zhang, MengYun

    2017-05-01

    In this paper, we study a simplified version of a West Nile virus model discussed by Lewis et al. [28], which was considered as a first approximation for the spatial spread of WNv. The basic reproduction number $R_0$ for the non-spatial epidemic model is defined and a threshold parameter $R_0 ^D$ for the corresponding problem with null Dirichlet boundary condition is introduced. We consider a free boundary problem with coupled system, which describes the diffusion of birds by a PDE and the movement of mosquitoes by a ODE. The risk index $R_0^F (t)$ associated with the disease in spatial setting is represented. Sufficient conditions for the WNv to eradicate or to spread are given. The asymptotic behavior of the solution to system when the spreading occurs are considered. It is shown that the initial number of infected populations, the diffusion rate of birds and the length of initial habitat exhibit important impacts on the vanishing or spreading of the virus. Numerical simulations are presented to illustrate the analytical results.

  5. Raptor mortality due to West Nile virus in the United States, 2002

    USGS Publications Warehouse

    Saito, E.K.; Sileo, L.; Green, D.E.; Meteyer, C.U.; McLaughlin, G.S.; Converse, K.A.; Docherty, D.E.

    2007-01-01

    West Nile virus (WNV) has affected many thousands of birds since it was first detected in North America in 1999, but the overall impact on wild bird populations is unknown. In mid-August 2002, wildlife rehabilitators and local wildlife officials from multiple states began reporting increasing numbers of sick and dying raptors, mostly red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus. Commonly reported clinical signs were nonspecific and included emaciation, lethargy, weakness, inability to perch, fly or stand, and nonresponse to danger. Raptor carcasses from 12 states were received, and diagnostic evaluation of 56 raptors implicated WNV infection in 40 (71%) of these cases. Histologically, nonsuppurative encephalitis and myocarditis were the salient lesions (79% and 61%, respectively). Other causes of death included lead poisoning, trauma, aspergillosis, and Salmonella spp. and Clostridium spp. infections. The reason(s) for the reported increase in raptor mortality due to WNV in 2002 compared with the previous WNV seasons is unclear, and a better understanding of the epizootiology and pathogenesis of the virus in raptor populations is needed. ?? Wildlife Disease Association 2007.

  6. A Snapshot Avian Surveillance Reveals West Nile Virus and Evidence of Wild Birds Participating in Toscana Virus Circulation.

    PubMed

    Hacioglu, Sabri; Dincer, Ender; Isler, Cafer Tayer; Karapinar, Zeynep; Ataseven, Veysel Soydal; Ozkul, Aykut; Ergunay, Koray

    2017-10-01

    Birds are involved in the epidemiology of several vector-borne viruses, as amplification hosts for viruses, dissemination vehicles for the vectors, and sources of emerging strains in cross-species transmission. Turkey provides diverse habitats for a variety of wild birds and is located along major bird migration routes. This study was undertaken to provide a cross-sectional screening of avian specimens for a spectrum of vector-borne viruses. The specimens were collected in Hatay province, in the Mediterranean coast of the Anatolian peninsula, located in the convergence zone of the known migration routes. Generic PCR assays were used for the detection of members of Nairovirus, Flavivirus, and Phlebovirus genera of Flaviviridae and Bunyaviridae families. The circulating viruses were characterized via sequencing and selected specimens were inoculated onto Vero cell lines for virus isolation. Specimens from 72 wild birds belonging in 8 orders and 14 species were collected. A total of 158 specimens that comprise 32 sera (20.3%) from 7 species and 126 tissues (79.7%) from 14 species were screened. Eight specimens (8/158, 5%), obtained from 4 individuals (4/72, 5.5%), were positive. West Nile virus (WNV) lineage 1 sequences were characterized in the spleen, heart, and kidney tissues from a lesser spotted eagle (Clanga pomarina), which distinctly clustered from sequences previously identified in Turkey. Toscana virus (TOSV) genotype A and B sequences were identified in brain and kidney tissues from a greater flamingo (Phoenicopterus roseus), a great white pelican (Pelecanus onocrotalus), and a black stork (Ciconia nigra), without successful virus isolation. Partial amino acid sequences of the viral nucleocapsid protein revealed previously unreported substitutions. This study documents the involvement of avians in WNV dispersion in Anatolia as well in TOSV life cycle.

  7. Seroprevalence of West Nile virus antibodies in equids in the North-East of Algeria and detection of virus circulation in 2014.

    PubMed

    Lafri, Ismail; Prat, Christine M; Bitam, Idir; Gravier, Patrick; Besbaci, Mohamed; Zeroual, Fayçal; Ben-Mahdi, Meriem Hind; Davoust, Bernard; Leparc-Goffart, Isabelle

    2017-02-01

    West Nile fever (WNF) is a viral disease of wild birds transmitted by mosquitoes. Humans and equids can also be affected and suffer from meningoencephalitis. In Algeria, since the 1994 epidemic, no data on WNV circulation was available until 2012. In September 2012, a fatal human case of WNV neuro-invasive infection occurred in Jijel province. This study describes the first seroprevalence study of West Nile virus (WNV) antibodies conducted in the equine population in Algeria. During 2014, serum samples were collected from 293 equids (222 donkeys and 71 horses) asymptomatic and unvaccinated for WNV in three localities in Northeastern wetlands of Algeria. Antibodies against WNV were found in 51 samples (seroprevalence 17.4%) of sampled equids, distributed as follows: 19 (seroprevalence 26.8%) horses and 32 (seroprevalence 14.4%) donkeys. Moreover 7 horses coming from Blida, in the center of Algeria, were tested before and after an 8-months stay in North-East Algeria. We observe a seroconversion in 2 horses, showing WNV circulation in 2014 in this specific region of Algeria. Copyright © 2016. Published by Elsevier Ltd.

  8. Spatiotemporal Co-occurrence of Flanders and West Nile Viruses Within Culex Populations in Shelby County, Tennessee.

    PubMed

    Lucero, D E; Carlson, T C; Delisle, J; Poindexter, S; Jones, T F; Moncayo, A C

    2016-05-01

    West Nile virus (WNV) and Flanders virus (FLAV) can cocirculate in Culex mosquitoes in parts of North America. A large dataset of mosquito pools tested for WNV and FLAV was queried to understand the spatiotemporal relationship between these two viruses in Shelby County, TN. We found strong evidence of global clustering (i.e., spatial autocorrelation) and overlapping of local clustering (i.e., Hot Spots based on Getis Ord Gi*) of maximum likelihood estimates (MLE) of infection rates (IR) during 2008-2013. Temporally, FLAV emerges and peaks on average 10.2 wk prior to WNV based on IR. Higher levels of WNV IR were detected within 3,000 m of FLAV-positive pool buffers than outside these buffers. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Passive West Nile virus antibody transfer from maternal Eastern Screech-Owls (Megascops asio) to progeny

    USGS Publications Warehouse

    Hahn, D.C.; Nemeth, N.M.; Edwards, E.; Bright, P.R.; Komar, N.

    2006-01-01

    Transovarial antibody transfer in owls has not been demonstrated for West Nile virus (WNV). We sampled chicks from captive adult WNV-antibody-positive Eastern Screech-Owls (Megascops asio) to evaluate the prevalence of transovarial maternal antibody transfer, as well as titers and duration of maternal antibodies. Twenty-four owlets aged 1 to 27 days old circulated detectable antibodies with neutralizing antibody titers ranging from 20 to 1600 (median 1:40). Demonstrating that WNV antibodies are passively transferred transovarially is important for accurate interpretation of serologic data from young birds.

  10. Integrating Environmental and Mosquito Data to Model Disease: Evaluating Alternative Modeling Approaches for Forecasting West Nile Virus in South Dakota, USA

    NASA Astrophysics Data System (ADS)

    Davis, J. K.; Vincent, G. P.; Hildreth, M.; Kightlinger, L.; Carlson, C.; Wimberly, M. C.

    2017-12-01

    South Dakota has the highest annual incidence of human cases of West Nile virus (WNV) in all US states, and human cases can vary wildly among years; predicting WNV risk in advance is a necessary exercise if public health officials are to respond efficiently and effectively to risk. Case counts are associated with environmental factors that affect mosquitoes, avian hosts, and the virus itself. They are also correlated with entomological risk indices obtained by trapping and testing mosquitoes. However, neither weather nor insect data alone provide a sufficient basis to make timely and accurate predictions, and combining them into models of human disease is not necessarily straightforward. Here we present lessons learned in three years of making real-time forecasts of this threat to public health. Various methods of integrating data from NASA's North American Land Data Assimilation System (NLDAS) with mosquito surveillance data were explored in a model comparison framework. We found that a model of human disease summarizing weather data (by polynomial distributed lags with seasonally-varying coefficients) and mosquito data (by a mixed-effects model that smooths out these sparse and highly-variable data) made accurate predictions of risk, and was generalizable enough to be recommended in similar applications. A model based on lagged effects of temperature and humidity provided the most accurate predictions. We also found that model accuracy was improved by allowing coefficients to vary smoothly throughout the season, giving different weights to different predictor variables during different parts of the season.

  11. Parasitic Cowbirds have increased immunity to West Nile and other mosquitoborne encephalitis viruses

    USGS Publications Warehouse

    Reisen, W.K.; Hahn, D.C.

    2006-01-01

    The rapid geographic spread of West Nile Virus [WNV, Flaviviridae, Flavivirus] across the United States has stimulated interest in comparative host infection studies of avian species to delineate competent reservoir hosts critical for viral amplification. Striking taxonomic differences in avian susceptibility have been noted, offering the opportunity to strategically select species on the basis of life history traits to examine aspects of pathogen virulence or host immunity. We hypothesized that avian brood parasites would show increased resistance to pathogens compared to related taxa, because they have been exposed in their evolutionary history to a wide array of infectious organisms from their different parenting species. The Brown-headed Cowbird (Molothrus ater) is a generalist brood parasite that parasitizes 200+ North American species. Elevated exposure to other species? parasites may have created an unusual degree of pathogen resistance. We compared the relative susceptibility of adult cowbirds to three closely-related non-parasitic species, Red-winged blackbirds, Tricolored blackbirds and Brewer?s blackbirds, to invading NY99 strain of WNV that is highly virulent for many passeriform birds. Previously we had experimentally infected these species with two North American mosquitoborne encephalitis viruses, western equine encephalomyelitis virus [WEEV, Togaviridae, Alphavirus] and St. Louis encephalitis virus [SLEV, Flaviviridae, Flavivirus]. Our results showed that cowbirds exhibited significantly lower viremia responses against all three viruses as well as after co-infection with both WEEV and WNV than did the three related, non-parasitic species. These data supported our hypothesis and indicated that cowbirds were more resistant to infection to both native and introduced viruses.

  12. Generation and characterization of West Nile pseudo-infectious reporter virus for antiviral screening.

    PubMed

    Zhang, Hong-Lei; Ye, Han-Qing; Deng, Cheng-Lin; Liu, Si-Qing; Shi, Pei-Yong; Qin, Cheng-Feng; Yuan, Zhi-Ming; Zhang, Bo

    2017-05-01

    West Nile virus (WNV), a mosquito-borne flavivirus, is an important neurotropic human pathogen. As a biosafety level-3 (BSL-3) agent, WNV is strictly to BSL-3 laboratories for experimentations, thus greatly hindering the development of vaccine and antiviral drug. Here, we developed a novel pseudo-infectious WNV reporter virus expressing the Gaussia luciferase (Gluc). A stable 293T NS1 cell line expressing NS1 was selected for trans-supplying NS1 protein to support the replication of WNV-ΔNS1 virus and WNV-ΔNS1-Gluc reporter virus with large-fragment deletion of NS1. WNV-ΔNS1 virus and WNV-Gluc-ΔNS1 reporter virus were confined to complete their replication cycle in this 293T NS1 cell line, displaying nearly identical growth kinetics to WT WNV although the viral titers were lower than those of WT WNV. The reporter gene was stably maintained in virus genome at least within three rounds of passage in 293T NS1 cell line. Using a known flaviviruses inhibitor, NITD008, we demonstrated that the pseudo-infectious WNV-Gluc-ΔNS1 could be used for antiviral screening. Furthermore, a high-throughput screening (HTS) assay in a 96-well format was optimized and validated using several known WNV inhibitors, indicating that the optimized HTS assay was suitable for high-throughput screening WNV inhibitors. Our work provides a stable and safe tool to handle WNV outside of a BSL-3 facility and facilitates high throughput screening for anti-WNV drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Detection of West Nile virus lineage 2 in the urine of acute human infections.

    PubMed

    Papa, Anna; Testa, Theodolinda; Papadopoulou, Elpida

    2014-12-01

    West Nile virus (WNV) lineage 2 emerged in Greece in 2010 and since then outbreaks in humans have been reported for four consecutive years. Laboratory diagnosis is based mainly on serology. A real-time RT-PCR was applied on urine samples obtained from 35 patients with acute WNV infection. WNV RNA was detected in 40% of the samples with cycle threshold (CT) values ranging from 26.95 to 39.89 (mean 33.11). WNV was isolated from two of four urine samples with low CT (<30). Viral load was not associated with patients' age, sex, day of illness, presence of WNV antibodies, and neurological symptoms. However, it seems that sample shipment and storage conditions are very important for virus detection and isolation. The usefulness of the WNV RNA detection in urine as a diagnostic tool of acute WNV infections is discussed. © 2014 Wiley Periodicals, Inc.

  14. Detection of West Nile virus genome and specific antibodies in Iranian encephalitis patients.

    PubMed

    Chinikar, S; Javadi, A; Ataei, B; Shakeri, H; Moradi, M; Mostafavi, E; Ghiasi, S M

    2012-08-01

    West Nile virus (WNV) is a mosquito-borne flavivirus which circulates in birds, horses and humans. An estimated 80% of WNV infections are asymptomatic. Fewer than 1% of infected persons develop neuroinvasive disease, which typically presents as encephalitis, meningitis, or acute flaccid paralysis. This study was conducted from January 2008 to June 2009 in Isfahan, Iran. Patients attending the emergency department with fever and loss of consciousness were consecutively included. Cerebrospinal fluids (CSF) were initially analysed through bacteriology and biochemistry examinations, resulting in those with evidence of meningitis being excluded. Patients' CSF and serum were diagnosed by serological and molecular assays. A total of 632 patients with fever and loss of consciousness were tested by CSF analyses. Samples of the remaining patients (39·4%) were referred for WNV investigation. Three (1·2%) of the patients were positive for both serum and CSF by RT-PCR, and six (2·4%) were positive only for IgG antibodies. History of insect bite, and blood transfusion and transplantation were risk factors for being positive by RT-PCR (P=0·048) and being IgG positive (P=0·024), respectively. The results of this study showed that the prevalence of West Nile fever is low in patients with encephalitis.

  15. The chicken 2'-5' oligoadenylate synthetase A inhibits the replication of West Nile virus.

    PubMed

    Tag-El-Din-Hassan, Hassan T; Sasaki, Nobuya; Moritoh, Kanako; Torigoe, Daisuke; Maeda, Akihiko; Agui, Takashi

    2012-08-01

    West Nile virus (WNV) is a pathogen to cause West Nile encephalitis when the infection occurs in the brain. Previous studies in mice identified the 2'-5' oligoadenylate synthetase 1b (Oas1b) gene as a determining factor for resistance to WNV infection. In addition, it has been suggested that human OAS1 and OASL are associated with the resistance to the WNV infection. WNV is maintained in nature through a complex life cycle involving wildbirds and mosquitoes. Birds are not only susceptible to the WNV, but also act as reservoir hosts, thus participating in the spread of the disease. It has previously been reported that chicken OASL possesses the oligoadenylate synthetase activity. However, until now the antiviral activity of chicken OASL has not been determined. In this study, we investigated the putative antiviral activity of chicken OASL by ectopic expression of this enzyme in mammalian cells and then infecting these cells with WNV replicon. We demonstrate that chicken OASL has an antiviral activity against the WNV. This is the first report to show that chicken OASL is associated with the resistance to the WNV infection.

  16. West Nile virus surveillance in Europe: moving towards an integrated animal-human-vector approach

    PubMed Central

    Gossner, Céline M; Marrama, Laurence; Carson, Marianne; Allerberger, Franz; Calistri, Paolo; Dilaveris, Dimitrios; Lecollinet, Sylvie; Morgan, Dilys; Nowotny, Norbert; Paty, Marie-Claire; Pervanidou, Danai; Rizzo, Caterina; Roberts, Helen; Schmoll, Friedrich; Van Bortel, Wim; Gervelmeyer, Andrea

    2017-01-01

    This article uses the experience of five European countries to review the integrated approaches (human, animal and vector) for surveillance and monitoring of West Nile virus (WNV) at national and European levels. The epidemiological situation of West Nile fever in Europe is heterogeneous. No model of surveillance and monitoring fits all, hence this article merely encourages countries to implement the integrated approach that meets their needs. Integration of surveillance and monitoring activities conducted by the public health authorities, the animal health authorities and the authorities in charge of vector surveillance and control should improve efficiency and save resources by implementing targeted measures. The creation of a formal interagency working group is identified as a crucial step towards integration. Blood safety is a key incentive for public health authorities to allocate sufficient resources for WNV surveillance, while the facts that an effective vaccine is available for horses and that most infected animals remain asymptomatic make the disease a lesser priority for animal health authorities. The examples described here can support other European countries wishing to strengthen their WNV surveillance or preparedness, and also serve as a model for surveillance and monitoring of other (vector-borne) zoonotic infections. PMID:28494844

  17. First detection of co-circulation of West Nile and Usutu viruses in equids in the south-west of Tunisia.

    PubMed

    Ben Hassine, T; De Massis, F; Calistri, P; Savini, G; BelHaj Mohamed, B; Ranen, A; Di Gennaro, A; Sghaier, S; Hammami, S

    2014-10-01

    In the last fifteen years, West Nile Virus (WNV) has dramatically expanded its geographic range and is now considered the most widespread arbovirus in the world. In Tunisia, West Nile Fever (WNF) outbreaks were reported in humans in 1997, 2003 and 2012. Usutu Virus (USUV), which is a 'new' emerging Flavivirus antigenically close to WNV, has never been reported in Tunisia. A serological investigation in 284 equids was conducted in 2012 in the southern west region of the country to assess the presence and prevalence of the WNV and USUV infection. Of the 284 samples tested by competitive enzyme-linked immunoassay, 129 were positive. Of these, 120 (42.3%) had WNV-specific neutralizing antibodies. The prevalence was significantly higher in areas closer to the oasis compared with that of the surrounding arid areas. Antibody titres against USUV were also reported in 10 equids. This was the first evidence of USUV circulation in Tunisia. Data recorded by this study indicate that WNV and USUV have circulated/are circulating in the region and that there is an urgent need to adapt the current surveillance programmes to this new scenario. © 2014 Blackwell Verlag GmbH.

  18. Experimental West Nile Virus Infection in Rabbits: An Alternative Model for Studying Induction of Disease and Virus Control

    PubMed Central

    Suen, Willy W.; Uddin, Muhammad J.; Wang, Wenqi; Brown, Vienna; Adney, Danielle R.; Broad, Nicole; Prow, Natalie A.; Bowen, Richard A.; Hall, Roy A.; Bielefeldt-Ohmann, Helle

    2015-01-01

    The economic impact of non-lethal human and equine West Nile virus (WNV) disease is substantial, since it is the most common presentation of the infection. Experimental infection with virulent WNV strains in the mouse and hamster models frequently results in severe neural infection and moderate to high mortality, both of which are not representative features of most human and equine infections. We have established a rabbit model for investigating pathogenesis and immune response of non-lethal WNV infection. Two species of rabbits, New Zealand White (Oryctolagus cuniculus) and North American cottontail (Sylvilagus sp.), were experimentally infected with virulent WNV and Murray Valley encephalitis virus strains. Infected rabbits exhibited a consistently resistant phenotype, with evidence of low viremia, minimal-absent neural infection, mild-moderate neuropathology, and the lack of mortality, even though productive virus replication occurred in the draining lymph node. The kinetics of anti-WNV neutralizing antibody response was comparable to that commonly seen in infected horses and humans. This may be explained by the early IFNα/β and/or γ response evident in the draining popliteal lymph node. Given this similarity to the human and equine disease, immunocompetent rabbits are, therefore, a valuable animal model for investigating various aspects of non-lethal WNV infections. PMID:26184326

  19. Identification and Characterization of Inhibitors of West Nile Virus

    PubMed Central

    Puig-Basagoiti, Francesc; Qing, Min; Dong, Hongping; Zhang, Bo; Zou, Gang; Yuan, Zhiming

    2011-01-01

    Although flaviviruses cause significant human diseases, no antiviral therapy is currently available for clinical treatment of these pathogens. To identify flavivirus inhibitors, we performed a high-throughput screening of compound libraries using cells containing luciferase-reporting replicon of West Nile viruses (WNV). Five novel small molecular inhibitors of WNV were identified from libraries containing 96,958 compounds. The inhibitors suppress epidemic strain of WNV in cell culture, with EC50 (50% effective concentration) values of <10 µM and TI (therapeutic index) values of >10. Viral titer reduction assays, using various flaviviruses and nonflaviviruses, showed that the compounds have distinct antiviral spectra. Mode-of-action analysis showed that the inhibitors block distinct steps of WNV replication: four compounds inhibit viral RNA syntheses, while the other compound suppresses both viral translation and RNA syntheses. Biochemical enzyme assays showed that two compounds selectively inhibit viral RNA-dependent RNA polymerase (RdRp), while another compound specifically inhibits both RdRp and methyltransferase. The identified compounds could potentially be developed for treatment of flavivirus infections. PMID:19501258

  20. Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses.

    PubMed

    Richard, Audrey Stéphanie; Zhang, Adam; Park, Sun-Jin; Farzan, Michael; Zong, Min; Choe, Hyeryun

    2015-11-24

    Phosphatidylserine (PS) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine (PE) is also a ligand for PS receptors and that this phospholipid mediates phagocytosis and viral entry. We show that a subset of PS receptors, including T-cell immunoglobulin (Ig) mucin domain protein 1 (TIM1), efficiently bind PE. We further show that PE is present in the virions of flaviviruses and filoviruses, and that the PE-specific cyclic peptide lantibiotic agent Duramycin efficiently inhibits the entry of West Nile, dengue, and Ebola viruses. The inhibitory effect of Duramycin is specific: it inhibits TIM1-mediated, but not L-SIGN-mediated, virus infection, and it does so by blocking virus attachment to TIM1. We further demonstrate that PE is exposed on the surface of apoptotic cells, and promotes their phagocytic uptake by TIM1-expressing cells. Together, our data show that PE plays a key role in TIM1-mediated virus entry, suggest that disrupting PE association with PS receptors is a promising broad-spectrum antiviral strategy, and deepen our understanding of the process by which apoptotic cells are cleared.

  1. West Nile virus outbreak in Phoenix, Arizona--2010: entomological observations and epidemiological correlations.

    PubMed

    Colborn, James M; Smith, Kirk A; Townsend, John; Damian, Dan; Nasci, Roger S; Mutebi, John-Paul

    2013-06-01

    In 2010, Arizona experienced an unusually early and severe outbreak of West Nile virus (WNV) centered in the southeast section of Maricopa County. Entomological data were collected before and during the outbreak, from May 25 through July 31, 2010, using the CO2-baited light trap monitoring system maintained by Maricopa County Vector Control. In the outbreak area, the most abundant species in the Town of Gilbert and in the area covered by the Roosevelt Water Conservation District was Culex quinquefasciatus, constituting 75.1% and 71.8% of the total number of mosquitoes collected, respectively. Vector index (VI) profiles showed that the abundance of infected Cx. quinquefasciatus peaked prior to human cases, suggesting that this species was involved in the initiation of the outbreak. In contrast, the VI profiles for Cx. tarsalis were consistently low, suggesting limited involvement in initiating and sustaining transmission. Taken together, the higher abundance and the VI profiles strongly suggest that Cx. quinquefasciatus was the primary vector for this outbreak. The VI profiles consistently showed that the abundance of infected mosquitoes peaked 1 to 2 wk before the peaks of human cases, suggesting that VI could have successfully been utilized to predict the WNV outbreak in Maricopa County, AZ, in 2010.

  2. Use of Testing for West Nile Virus and Other Arboviruses.

    PubMed

    Vanichanan, Jakapat; Salazar, Lucrecia; Wootton, Susan H; Aguilera, Elizabeth; Garcia, Melissa N; Murray, Kristy O; Hasbun, Rodrigo

    2016-09-01

    In the United States, the most commonly diagnosed arboviral disease is West Nile virus (WNV) infection. Diagnosis is made by detecting WNV IgG or viral genomic sequences in serum or cerebrospinal fluid. To determine frequency of this testing in WNV-endemic areas, we examined the proportion of tests ordered for patients with meningitis and encephalitis at 9 hospitals in Houston, Texas, USA. We identified 751 patients (567 adults, 184 children), among whom 390 (52%) experienced illness onset during WNV season (June-October). WNV testing was ordered for 281 (37%) of the 751; results indicated acute infection for 32 (11%). Characteristics associated with WNV testing were acute focal neurologic deficits; older age; magnetic resonance imaging; empirically prescribed antiviral therapy; worse clinical outcomes: and concomitant testing for mycobacterial, fungal, or other viral infections. Testing for WNV is underutilized, and testing of patients with more severe disease raises the possibility of diagnostic bias in epidemiologic studies.

  3. Identification and characterization of microRNAs and their target genes from Nile tilapia (Oreochromis niloticus).

    PubMed

    Huang, Yong; Ma, Xiu Ying; Yang, You Bing; Ren, Hong Tao; Sun, Xi Hong; Wang, Li Rui

    MicroRNAs (miRNAs) are a class of small single-stranded, endogenous 21-22 nt non-coding RNAs that regulate their target mRNA levels by causing either inactivation or degradation of the mRNAs. In recent years, miRNA genes have been identified from mammals, insects, worms, plants, and viruses. In this research, bioinformatics approaches were used to predict potential miRNAs and their targets in Nile tilapia from the expressed sequence tag (EST) and genomic survey sequence (GSS) database, respectively, based on the conservation of miRNAs in many animal species. A total of 19 potential miRNAs were detected following a range of strict filtering criteria. To test the validity of the bioinformatics method, seven predicted Nile tilapia miRNA genes were selected for further biological validation, and their mature miRNA transcripts were successfully detected by stem-loop RT-PCR experiments. Using these potential miRNAs, we found 56 potential targets in this species. Most of the target mRNAs appear to be involved in development, metabolism, signal transduction, transcription regulation and stress responses. Overall, our findings will provide an important foundation for further research on miRNAs function in the Nile tilapia.

  4. Characterization of Rabensburg Virus, a Flavivirus Closely Related to West Nile Virus of the Japanese Encephalitis Antigenic Group

    PubMed Central

    Aliota, Matthew T.; Jones, Susan A.; Dupuis, Alan P.; Ciota, Alexander T.; Hubalek, Zdenek; Kramer, Laura D.

    2012-01-01

    Rabensburg virus (RABV), a Flavivirus with ∼76% nucleotide and 90% amino acid identity with representative members of lineage one and two West Nile virus (WNV), previously was isolated from Culex pipiens and Aedes rossicus mosquitoes in the Czech Republic, and phylogenetic and serologic analyses demonstrated that it was likely a new lineage of WNV. However, no direct link between RABV and human disease has been definitively established and the extent to which RABV utilizes the typical WNV transmission cycle is unknown. Herein, we evaluated vector competence and capacity for vertical transmission (VT) in Cx. pipiens; in vitro growth on avian, mammalian, and mosquito cells; and infectivity and viremia production in birds. RABV infection and replication only were detected on mosquito cells. Experimentally inoculated birds did not become infected. Cx. pipiens had poor peroral vector competence and a higher VT rate as compared to US-WNV in Cx. pipiens. As a result, we postulate that RABV is an intermediate between the mosquito-specific and horizontally transmitted flaviviruses. PMID:22724010

  5. Inactivation of West Nile Virus in Serum with Heat, Ionic Detergent, and Reducing Agent for Proteomic Applications (Open Access Publisher’s Version)

    DTIC Science & Technology

    2017-05-19

    LightCycler® 96 desktop software. Positive and negative samples were identified using the “ Qualitative Detection” analysis function using the default...Institute of Infectious Diseases, Fort Detrick, MD 21702, United States A R T I C L E I N F O Keywords: West Nile virus Virus inactivation Sample buffer... samples using a commercially available SDS- PAGE sample buffer for proteomic studies. Using this method, we demonstrate its utility by identification

  6. [Detection of West Nile virus in human samples: follow-up studies during the 2015 seasonal period].

    PubMed

    Nagy, Anna; Nagy, Orsolya; Bán, Enikő; Molnár, Eszter; Müller, Zsófia; Orbán, Márton; Kecskés, Borbála; Harsányi, Emese Henriett; Kővágó, Levente; Jobbágy, Lajos; Németh, Zoltán; Várnai, Zsuzsanna; Takács, Mária

    2017-05-01

    West Nile virus, a mosquito-borne viral zoonosis is responsible for human infections in Hungary. Laboratory diagnosis is based on serological tests, however the application of molecular methods has been appreciated. The aim of the study was to investigate blood, cerebrospinal-fluid and urine samples of acutely ill patients and to follow-up PCR positive cases to ascertain the length of virus excretion. Clinical specimens were examined by indirect-immunofluorescent, haemagglutination-inhibition, two PCR tests and Sanger-sequencing. Virus isolation in case of two patients was successful. A follow-up study could be carried out in case of 5 patients. Viral nucleic acid was detectable in urine even for several weeks after symptom onset and viral RNA was present at higher concentration compared with other samples. PCR analysis of urine could provide useful epidemiological and diagnostic information. Therefore, it is recommended to collect urine samples in order to supplement the serological diagnosis. Orv Hetil. 2017; 158(20): 791-796.

  7. Environmental and biological factors influencing Culex pipiens quinquefasciatus (Diptera: Culicidae) vector competence for West Nile Virus.

    PubMed

    Richards, Stephanie L; Lord, Cynthia C; Pesko, Kendra N; Tabachnick, Walter J

    2010-07-01

    Interactions between environmental and biological factors affect the vector competence of Culex pipiens quinquefasciatus for West Nile virus. Three age cohorts from two Cx. p. quinquefasciatus colonies were fed blood containing a low- or high-virus dose, and each group was held at two different extrinsic incubation temperatures (EIT) for 13 days. The colonies differed in the way that they responded to the effects of the environment on vector competence. The effects of mosquito age on aspects of vector competence were dependent on the EIT and dose, and they changed depending on the colony. Complex interactions must be considered in laboratory studies of vector competence, because the extent of the genetic and environmental variation controlling vector competence in nature is largely unknown. Differences in the environmental (EIT and dose) and biological (mosquito age and colony) effects from previous studies of Cx. p. quinquefasciatus vector competence for St. Louis encephalitis virus are discussed.

  8. Variation in interferon sensitivity and induction between Usutu and West Nile (lineages 1 and 2) viruses.

    PubMed

    Cacciotti, Giulia; Caputo, Beniamino; Selvaggi, Carla; la Sala, Andrea; Vitiello, Laura; Diallo, Diawo; Ceianu, Cornelia; Antonelli, Guido; Nowotny, Norbert; Scagnolari, Carolina

    2015-11-01

    Given the pivotal role of monocyte-derived dendritic cells (DCs) in determining the magnitude of the antiviral innate immune response, we sought to determine whether Usutu virus (USUV) and West Nile virus (WNV) lineages (L)1 and L2 can infect DCs and affect the rate of type I interferon (IFN) activation. The sensitivity of these viruses to types I and III IFNs was also compared. We found that USUV can infect DCs, induce higher antiviral activities, IFN alpha subtypes and the IFN stimulated gene (ISG)15 pathway, and is more sensitive to types I and III IFNs than WNVs. In contrast, we confirmed that IFN alpha/beta subtypes were more effective against WNV L2 than WNV L1. However, the replication kinetics, induction of IFN alpha subtypes and ISGs in DCs and the sensitivity to IFN lambda 1-3 did not differ between WNV L1 and L2. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The composition of West Nile virus lipid envelope unveils a role of sphingolipid metabolism in flavivirus biogenesis.

    PubMed

    Martín-Acebes, Miguel A; Merino-Ramos, Teresa; Blázquez, Ana-Belén; Casas, Josefina; Escribano-Romero, Estela; Sobrino, Francisco; Saiz, Juan-Carlos

    2014-10-01

    West Nile virus (WNV) is an emerging zoonotic mosquito-borne flavivirus responsible for outbreaks of febrile illness and meningoencephalitis. The replication of WNV takes place on virus-modified membranes from the endoplasmic reticulum of the host cell, and virions acquire their envelope by budding into this organelle. Consistent with this view, the cellular biology of this pathogen is intimately linked to modifications of the intracellular membranes, and the requirement for specific lipids, such as cholesterol and fatty acids, has been documented. In this study, we evaluated the impact of WNV infection on two important components of cellular membranes, glycerophospholipids and sphingolipids, by mass spectrometry of infected cells. A significant increase in the content of several glycerophospholipids (phosphatidylcholine, plasmalogens, and lysophospholipids) and sphingolipids (ceramide, dihydroceramide, and sphingomyelin) was noticed in WNV-infected cells, suggesting that these lipids have functional roles during WNV infection. Furthermore, the analysis of the lipid envelope of WNV virions and recombinant virus-like particles revealed that their envelopes had a unique composition. The envelopes were enriched in sphingolipids (sphingomyelin) and showed reduced levels of phosphatidylcholine, similar to sphingolipid-enriched lipid microdomains. Inhibition of neutral sphingomyelinase (which catalyzes the hydrolysis of sphingomyelin into ceramide) by either pharmacological approaches or small interfering RNA-mediated silencing reduced the release of flavivirus virions as well as virus-like particles, suggesting a role of sphingomyelin-to-ceramide conversion in flavivirus budding and confirming the importance of sphingolipids in the biogenesis of WNV. Importance: West Nile virus (WNV) is a neurotropic flavivirus spread by mosquitoes that can infect multiple vertebrate hosts, including humans. There is no specific vaccine or therapy against this pathogen licensed for

  10. The Composition of West Nile Virus Lipid Envelope Unveils a Role of Sphingolipid Metabolism in Flavivirus Biogenesis

    PubMed Central

    Martín-Acebes, Miguel A.; Merino-Ramos, Teresa; Blázquez, Ana-Belén; Casas, Josefina; Escribano-Romero, Estela

    2014-01-01

    ABSTRACT West Nile virus (WNV) is an emerging zoonotic mosquito-borne flavivirus responsible for outbreaks of febrile illness and meningoencephalitis. The replication of WNV takes place on virus-modified membranes from the endoplasmic reticulum of the host cell, and virions acquire their envelope by budding into this organelle. Consistent with this view, the cellular biology of this pathogen is intimately linked to modifications of the intracellular membranes, and the requirement for specific lipids, such as cholesterol and fatty acids, has been documented. In this study, we evaluated the impact of WNV infection on two important components of cellular membranes, glycerophospholipids and sphingolipids, by mass spectrometry of infected cells. A significant increase in the content of several glycerophospholipids (phosphatidylcholine, plasmalogens, and lysophospholipids) and sphingolipids (ceramide, dihydroceramide, and sphingomyelin) was noticed in WNV-infected cells, suggesting that these lipids have functional roles during WNV infection. Furthermore, the analysis of the lipid envelope of WNV virions and recombinant virus-like particles revealed that their envelopes had a unique composition. The envelopes were enriched in sphingolipids (sphingomyelin) and showed reduced levels of phosphatidylcholine, similar to sphingolipid-enriched lipid microdomains. Inhibition of neutral sphingomyelinase (which catalyzes the hydrolysis of sphingomyelin into ceramide) by either pharmacological approaches or small interfering RNA-mediated silencing reduced the release of flavivirus virions as well as virus-like particles, suggesting a role of sphingomyelin-to-ceramide conversion in flavivirus budding and confirming the importance of sphingolipids in the biogenesis of WNV. IMPORTANCE West Nile virus (WNV) is a neurotropic flavivirus spread by mosquitoes that can infect multiple vertebrate hosts, including humans. There is no specific vaccine or therapy against this pathogen licensed

  11. Noncoding Subgenomic Flavivirus RNA: Multiple Functions in West Nile Virus Pathogenesis and Modulation of Host Responses

    PubMed Central

    Roby, Justin A.; Pijlman, Gorben P.; Wilusz, Jeffrey; Khromykh, Alexander A.

    2014-01-01

    Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA) derived from the 3' untranslated region (UTR). sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'–3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-α/β by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated. PMID:24473339

  12. Terminal structures of West Nile virus genomic RNA and their interactions with viral NS5 protein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dong Hongping; Zhang Bo; Shi Peiyong

    2008-11-10

    Genome cyclization is essential for flavivirus replication. We used RNases to probe the structures formed by the 5'-terminal 190 nucleotides and the 3'-terminal 111 nucleotides of the West Nile virus (WNV) genomic RNA. When analyzed individually, the two RNAs adopt stem-loop structures as predicted by the thermodynamic-folding program. However, when mixed together, the two RNAs form a duplex that is mediated through base-pairings of two sets of RNA elements (5'CS/3'CSI and 5'UAR/3'UAR). Formation of the RNA duplex facilitates a conformational change that leaves the 3'-terminal nucleotides of the genome (position - 8 to - 16) to be single-stranded. Viral NS5more » binds specifically to the 5'-terminal stem-loop (SL1) of the genomic RNA. The 5'SL1 RNA structure is essential for WNV replication. The study has provided further evidence to suggest that flavivirus genome cyclization and NS5/5'SL1 RNA interaction facilitate NS5 binding to the 3' end of the genome for the initiation of viral minus-strand RNA synthesis.« less

  13. Geographic variations of the bird-borne structural risk of West Nile virus circulation in Europe

    PubMed Central

    Durand, Benoit; Tran, Annelise; Balança, Gilles

    2017-01-01

    The structural risk of West Nile Disease results from the usual functioning of the socio-ecological system, which may favour the introduction of the pathogen, its circulation and the occurrence of disease cases. Its geographic variations result from the local interactions between three components: (i) reservoir hosts, (ii) vectors, both characterized by their diversity, abundance and competence, (iii) and the socio-economic context that impacts the exposure of human to infectious bites. We developed a model of bird-borne structural risk of West Nile Virus (WNV) circulation in Europe, and analysed the association between the geographic variations of this risk and the occurrence of WND human cases between 2002 and 2014. A meta-analysis of WNV serosurveys conducted in wild bird populations was performed to elaborate a model of WNV seropositivity in European bird species, considered a proxy for bird exposure to WNV. Several eco-ethological traits of bird species were linked to seropositivity and the statistical model adequately fitted species-specific seropositivity data (area under the ROC curve: 0.85). Combined with species distribution maps, this model allowed deriving geographic variations of the bird-borne structural risk of WNV circulation. The association between this risk, and the occurrence of WND human cases across the European Union was assessed. Geographic risk variations of bird-borne structural risk allowed predicting WND case occurrence in administrative districts of the EU with a sensitivity of 86% (95% CI: 0.79–0.92), and a specificity of 68% (95% CI: 0.66–0.71). Disentangling structural and conjectural health risks is important for public health managers as risk mitigation procedures differ according to risk type. The results obtained show promise for the prevention of WND in Europe. Combined with analyses of vector-borne structural risk, they should allow designing efficient and targeted prevention measures. PMID:29023472

  14. Experimental North American West Nile Virus Infection in the Red-legged Partridge (Alectoris rufa).

    PubMed

    Gamino, V; Escribano-Romero, E; Blázquez, A-B; Gutiérrez-Guzmán, A-V; Martín-Acebes, M-Á; Saiz, J-C; Höfle, U

    2016-05-01

    After the introduction of West Nile virus (WNV) into North America, bird mortalities associated with West Nile disease have dramatically increased in this continent and, to a lesser extent, in Europe. The different West Nile disease incidence in birds in these 2 continents demands an explanation, and experimental studies can provide important information. The authors inoculated thirteen 9-week-old red-legged partridges (Alectoris rufa) with 10(7)plaque-forming units of a WNV strain isolated in New York in 1999. The objective was to study the pathogenesis of the infection in a native Euro-Mediterranean bird species with a WNV strain known to be highly pathogenic for numerous native American bird species. Additionally, the authors evaluated the dynamics of inflammatory cell activation and recruitment into the brain. WNV was detected in tissues 3 days postinoculation (dpi), and the birds developed macroscopic and microscopic lesions. Two partridges succumbed to the disease. The most affected tissues were the heart, brain, and spinal cord. The main microscopic findings were the presence of mononuclear infiltrates in the heart and brain, gliosis, and degeneration and necrosis of cardiomyocytes and neurons. These lesions were aggravated in the birds that died or were euthanized 7 dpi or later. In the brain, there was an upregulation of microglial cells and astrocytes and an increase in the number of T cells, especially after 7 dpi. These results show that this WNV strain is of moderate virulence for the red-legged partridge and that WNV-infected red-legged partridges develop an immune cell response in the brain similar to that of mammals. © The Author(s) 2015.

  15. Predicting solvatochromic shifts and colours of a solvated organic dye: The example of nile red

    NASA Astrophysics Data System (ADS)

    Zuehlsdorff, T. J.; Haynes, P. D.; Payne, M. C.; Hine, N. D. M.

    2017-03-01

    The solvatochromic shift, as well as the change in colour of the simple organic dye nile red, is studied in two polar and two non-polar solvents in the context of large-scale time-dependent density-functional theory (TDDFT) calculations treating large parts of the solvent environment from first principles. We show that an explicit solvent representation is vital to resolve absorption peak shifts between nile red in n-hexane and toluene, as well as acetone and ethanol. The origin of the failure of implicit solvent models for these solvents is identified as being due to the strong solute-solvent interactions in form of π-stacking and hydrogen bonding in the case of toluene and ethanol. We furthermore demonstrate that the failures of the computationally inexpensive Perdew-Burke-Ernzerhof (PBE) functional in describing some features of the excited state potential energy surface of the S1 state of nile red can be corrected for in a straightforward fashion, relying only on a small number of calculations making use of more sophisticated range-separated hybrid functionals. The resulting solvatochromic shifts and predicted colours are in excellent agreement with experiment, showing the computational approach outlined in this work to yield very robust predictions of optical properties of dyes in solution.

  16. Generation of a recombinant West Nile virus stably expressing the Gaussia luciferase for neutralization assay.

    PubMed

    Zhang, Pan-Tao; Shan, Chao; Li, Xiao-Dan; Liu, Si-Qing; Deng, Cheng-Lin; Ye, Han-Qing; Shang, Bao-Di; Shi, Pei-Yong; Lv, Ming; Shen, Bei-Fen; Qin, Cheng-Feng; Zhang, Bo

    2016-01-04

    West Nile virus (WNV) is a neurotropic human pathogen that has caused increasing infected cases over recent years. There is currently no licensed vaccine or effective drug for prevention and treatment of WNV infection in humans. To facilitate antiviral drug discovery and neutralizing antibody detection, a WNV cDNA clone containing a luciferase reporter gene was constructed through incorporating Gaussia luciferase (Gluc) gene within the capsid-coding region of WNV genome. Transfection of BHK-21 cells with the cDNA clone-derived RNA generated luciferase reporter WNV (WNV-Gluc) and the stable WNV-Gluc with high titers (>10(7)PFU/ml) was obtained through plaque purification. Luciferase activity was used to effectively quantify the viral production of WNV-Gluc. Using the reporter virus WNV-Gluc, we developed a luciferase based assay in a 12-well format for evaluating neutralizing antibodies. The reporter virus could be a powerful tool for epidemiological investigation of WNV, vaccine evaluation, antiviral drug screening, and the study of WNV replication and pathogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Inhibition of West Nile Virus replication by retrovirus-delivered small interfering RNA in human neuroblastoma cells.

    PubMed

    Yang, Yongbo; Wu, Chengxiang; Wu, Jianguo; Nerurkar, Vivek R; Yanagihara, Richard; Lu, Yuanan

    2008-05-01

    West Nile virus (WNV) has been responsible for the largest outbreaks of arboviral encephalitis in U.S. history. No specific drug is currently available for the effective treatment of WNV infection. To exploit RNA interference as a potential therapeutic approach, a Moloney murine leukemia virus-based retrovirus vector was used to effectively deliver WNV-specific small interfering RNA (siRNA) into human neuroblastoma HTB-11 cells. Viral plaque assays demonstrated that transduced cells were significantly refractory to WNV replication, as compared to untransduced control cells (P < 0.05), which correlated with the reduced expression of target viral genes and respective viral proteins. Therefore, retrovirus-mediated delivery of siRNA for gene silencing can be used to study the specific functions of viral genes associated with replication and may have potential therapeutic applications.

  18. The insect-specific Palm Creek virus modulates West Nile virus infection in and transmission by Australian mosquitoes.

    PubMed

    Hall-Mendelin, Sonja; McLean, Breeanna J; Bielefeldt-Ohmann, Helle; Hobson-Peters, Jody; Hall, Roy A; van den Hurk, Andrew F

    2016-07-25

    Insect-specific viruses do not replicate in vertebrate cells, but persist in mosquito populations and are highly prevalent in nature. These viruses may naturally regulate the transmission of pathogenic vertebrate-infecting arboviruses in co-infected mosquitoes. Following the isolation of the first Australian insect-specific flavivirus (ISF), Palm Creek virus (PCV), we investigated routes of infection and transmission of this virus in key Australian arbovirus vectors and its impact on replication and transmission of West Nile virus (WNV). Culex annulirostris, Aedes aegypti and Aedes vigilax were exposed to PCV, and infection, replication and transmission rates in individual mosquitoes determined. To test whether the virus could be transmitted vertically, progeny reared from eggs oviposited by PCV-inoculated Cx. annulirostris were analysed for the presence of PCV. To assess whether prior infection of mosquitoes with PCV could also suppress the transmission of pathogenic flaviviruses, PCV positive or negative Cx. annulirostris were subsequently exposed to WNV. No PCV-infected Cx. annulirostris were detected 16 days after feeding on an infectious blood meal. However, when intrathoracically inoculated with PCV, Cx. annulirostris infection rates were 100 %. Similar rates of infection were observed in Ae. aegypti (100 %) and Ae. vigilax (95 %). Notably, PCV was not detected in any saliva expectorates collected from any of these species. PCV was not detected in 1038 progeny reared from 59 PCV-infected Cx. annulirostris. After feeding on a blood meal containing 10(7) infectious units of WNV, significantly fewer PCV-infected Cx. annulirostris were infected or transmitted WNV compared to PCV negative mosquitoes. Immunohistochemistry revealed that PCV localized in the midgut epithelial cells, which are the first site of infection with WNV. Our results indicate that PCV cannot infect Cx. annulirostris via the oral route, nor be transmitted in saliva or vertically to progeny

  19. Plant-made vaccines against West Nile virus are potent, safe, and economically feasible

    PubMed Central

    Chen, Qiang

    2015-01-01

    The threat of West Nile virus (WNV) epidemics with increasingly severe neuroinvasive infections demands the development and licensing of effective vaccines. To date, vaccine candidates based on inactivated, live-attenuated, or chimeric virus, and viral DNA and WNV protein subunits have been developed. Some have been approved for veterinary use or are under clinical investigation, yet no vaccine has been licensed for human use. Reaching the milestone of a commercialized human vaccine, however, may largely depend on the economics of vaccine production. Analysis suggests that currently only novel low-cost production technologies would allow vaccination to outcompete the cost of surveillance and clinical treatment. Here, we review progress using plants to address the economic challenges of WNV vaccine production. The advantages of plants as hosts for vaccine production in cost, speed and scalability, especially those of viral vector-based transient expression systems, are discussed. The progress in developing WNV subunit vaccines in plants is reviewed within the context of their expression, characterization, downstream processing, and immunogenicity in animal models. The development of vaccines based on enveloped and non-enveloped virus-like particles is also discussed. These advancements suggest that plants may provide a production platform that offers potent, safe and affordable human vaccines against WNV. PMID:25676782

  20. Surveillance potential of non-native Hawaiian birds for detection of West Nile Virus

    USGS Publications Warehouse

    Hofmeister, Erik K.; Dusek, Robert J.; Brand, Christopher J.

    2015-01-01

    West Nile virus (WNV) was first detected in North America in 1999. Alaska and Hawaii (HI) remain the only U.S. states in which transmission of WNV has not been detected. Dead bird surveillance has played an important role in the detection of the virus geographically, as well as temporally. In North America, corvids have played a major role in WNV surveillance; however, the only corvid in HI is the endangered Hawaiian crow that exists only in captivity, thus precluding the use of this species for WNV surveillance in HI. To evaluate the suitability of alternate avian species for WNV surveillance, we experimentally challenged seven abundant non-native bird species present in HI with WNV and compared mortality, viremia, oral shedding of virus, and seroconversion. For detection of WNV in oral swabs, we compared viral culture, reverse-transcriptase polymerase chain reaction, and the RAMP® test. For detection of antibodies to WNV, we compared an indirect and a competitive enzyme-linked immunoassay. We found four species (house sparrow, house finch, Japanese white-eye, and Java sparrow) that may be useful in dead bird surveillance for WNV; while common myna, zebra dove, and spotted dove survived infection and may be useful in serosurveillance.

  1. Supramolecular peptide hydrogel adjuvanted subunit vaccine elicits protective antibody responses against West Nile virus.

    PubMed

    Friedrich, Brian M; Beasley, David W C; Rudra, Jai S

    2016-11-04

    A crucial issue in vaccine development is to balance safety with immunogenicity. The low immunogenicity of most subunit antigens warrants a search for adjuvants able to stimulate both cell-mediated and humoral immunity. In recent years, successful applications of nanotechnology and bioengineering in the field of vaccine development have enabled the production of novel adjuvant technologies. In this work, we investigated totally synthetic and supramolecular peptide hydrogels as novel vaccine adjuvants in conjunction with the immunoprotective envelope protein domain III (EIII) of West Nile virus as an immunogen in a mouse model. Our results indicate that, compared to the clinically approved adjuvant alum, peptide hydrogel adjuvanted antigen elicited stronger antibody responses and conferred significant protection against mortality after virus challenge. The high chemical definition and biocompatibility of self-assembling peptide hydrogels makes them attractive as immune adjuvants for the production of subunit vaccines against viral and bacterial infections where antibody-mediated protection is desirable. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Evidence for West Nile virus spillover into the squirrel population in Atlanta, Georgia.

    PubMed

    Bisanzio, Donal; McMillan, Joseph R; Barreto, Josafá Gonçalves; Blitvich, Bradley J; Mead, Daniel G; O'Connor, Josh; Kitron, Uriel

    2015-05-01

    In the United States, spillover of West Nile virus (WNV) into wild mammal populations has been reported since the introduction of the virus into the New World in 1999. Eastern gray squirrels (Sciurus carolinensis) exhibit a high seroprevalence for WNV in urban settings where high virus circulation and human spillover have been reported. In Atlanta, Georgia, human cases of WNV are uncommon despite high infection rates in birds and mosquitoes. In this study, we evaluated WNV exposure of eastern gray squirrels in a WNV hot spot in Atlanta. Gray squirrels were live-trapped in Grant Park, Atlanta, during July-October, 2012, and a census was conducted to estimate squirrel density in the study site. Sera from trapped animals were tested for circulating virus-by-virus isolation in cell culture and for WNV-specific antibodies by enzyme-linked immunosorbent assay and plaque reduction neutralization test. Mosquitoes were collected at the same location and tested for virus isolation. Among the 69 collected squirrels, 25 (36.2%) tested positive for WNV antibodies, although none were viremic. Seroprevalence was lower in juveniles (18.8%) than in adults (37.5%), but this difference was not statistically significant. Gender and squirrel density had no effect on seroprevalence. Seasonality of squirrel seroprevalence and of mosquito infection were significantly associated, both peaking in August. No difference in squirrel exposure was detected across the collection sites. We report a high degree of WNV exposure in squirrels in Grant Park that was correlated with seasonality of mosquito infection. The detection of antibodies in juveniles suggests that circulation of WNV in the surveyed population is ongoing. Eastern gray squirrels may be suitable indicators for virus amplification and for risk of human spillover on a local scale in urban settings.

  3. Experimental West Nile virus infection in Eastern Screech Owls (Megascops asio)

    USGS Publications Warehouse

    Nemeth, N.M.; Hahn, D.C.; Gould, D.H.; Bowen, R.A.

    2006-01-01

    Eastern Screech Owls (EASOs) were experimentally infected with the pathogenic New York 1999 strain of West Nile virus (WNV) by subcutaneous injection or per os. Two of nine subcutaneously inoculated birds died or were euthanatized on 8 or 9 days postinfection (DPI) after <24 hr of lethargy and recumbency. All subcutaneously inoculated birds developed levels of viremia that are likely infectious to mosquitoes, with peak viremia levels ranging from 105.0 to 109.6 plaque-forming units/ml. Despite the viremia, the remaining seven birds did not display signs of illness. All birds alive beyond 5 DPI seroconverted, although the morbid birds demonstrated significantly lower antibody titers than the clinically normal birds. Cagemates of infected birds did not become infected. One of five orally exposed EASOs became viremic and seroconverted, whereas WNV infection in the remaining four birds was not evident. All infected birds shed virus via the oral and cloacal route. Early during infection, WNV targeted skin, spleen, esophagus, and skeletal muscle. The two morbid owls had myocardial and skeletal muscle necrosis and mild encephalitis and nephritis, whereas some of the clinically healthy birds that were sacrificed on 14 DPI had myocardial arteritis and renal phlebitis. WNV is a significant pathogen of EASOs, causing pathologic lesions with varying clinical outcomes.

  4. Ecology of West Nile virus across four European countries: empirical modelling of the Culex pipiens abundance dynamics as a function of weather.

    PubMed

    Groen, Thomas A; L'Ambert, Gregory; Bellini, Romeo; Chaskopoulou, Alexandra; Petric, Dusan; Zgomba, Marija; Marrama, Laurence; Bicout, Dominique J

    2017-10-26

    Culex pipiens is the major vector of West Nile virus in Europe, and is causing frequent outbreaks throughout the southern part of the continent. Proper empirical modelling of the population dynamics of this species can help in understanding West Nile virus epidemiology, optimizing vector surveillance and mosquito control efforts. But modelling results may differ from place to place. In this study we look at which type of models and weather variables can be consistently used across different locations. Weekly mosquito trap collections from eight functional units located in France, Greece, Italy and Serbia for several years were combined. Additionally, rainfall, relative humidity and temperature were recorded. Correlations between lagged weather conditions and Cx. pipiens dynamics were analysed. Also seasonal autoregressive integrated moving-average (SARIMA) models were fitted to describe the temporal dynamics of Cx. pipiens and to check whether the weather variables could improve these models. Correlations were strongest between mean temperatures at short time lags, followed by relative humidity, most likely due to collinearity. Precipitation alone had weak correlations and inconsistent patterns across sites. SARIMA models could also make reasonable predictions, especially when longer time series of Cx. pipiens observations are available. Average temperature was a consistently good predictor across sites. When only short time series (~ < 4 years) of observations are available, average temperature can therefore be used to model Cx. pipiens dynamics. When longer time series (~ > 4 years) are available, SARIMAs can provide better statistical descriptions of Cx. pipiens dynamics, without the need for further weather variables. This suggests that density dependence is also an important determinant of Cx. pipiens dynamics.

  5. Prediction of future climate change for the Blue Nile, using RCM nested in GCM

    NASA Astrophysics Data System (ADS)

    Sayed, E.; Jeuland, M.; Aty, M.

    2009-04-01

    Although the Nile River Basin is rich in natural resources, it faces many challenges. Rainfall is highly variable across the region, on both seasonal and inter-annual scales. This variability makes the region vulnerable to droughts and floods. Many development projects involving Nile waters are currently underway, or being studied. These projects will lead to land-use patterns changes and water distribution and availability. It is thus important to assess the effects of a) these projects and b) evolving water resource management and policies, on regional hydrological processes. This paper seeks to establish a basis for evaluation of such impacts within the Blue Nile River sub-basin, using the RegCM3 Regional Climate Model to simulate interactions between the land surface and climatic processes. We first present results from application of this RCM model nested with downscaled outputs obtained from the ECHAM5/MPI-OM1 transient simulations for the 20th Century. We then investigate changes associated with mid-21st century emissions forcing of the SRES A1B scenario. The results obtained from the climate model are then fed as inputs to the Nile Forecast System (NFS), a hydrologic distributed rainfall runoff model of the Nile Basin, The interaction between climatic and hydrological processes on the land surface has been fully coupled. Rainfall patterns and evaporation rates have been generated using RegCM3, and the resulting runoff and Blue Nile streamflow patterns have been simulated using the NFS. This paper compares the results obtained from the RegCM3 climate model with observational datasets for precipitation and temperature from the Climate Research Unit (UK) and the NASA Goddard Space Flight Center GPCP (USA) for 1985-2000. The validity of the streamflow predictions from the NFS is assessed using historical gauge records. Finally, we present results from modeling of the A1B emissions scenario of the IPCC for the years 2034-2055. Our results indicate that future

  6. A novel reverse genetics system for production of infectious West Nile virus using homologous recombination in mammalian cells.

    PubMed

    Kobayashi, Shintaro; Yoshii, Kentaro; Hirano, Minato; Muto, Memi; Kariwa, Hiroaki

    2017-02-01

    Reverse genetics systems facilitate investigation of many aspects of the life cycle and pathogenesis of viruses. However, genetic instability in Escherichia coli has hampered development of a reverse genetics system for West Nile virus (WNV). In this study, we developed a novel reverse genetics system for WNV based on homologous recombination in mammalian cells. Introduction of the DNA fragment coding for the WNV structural protein together with a DNA-based replicon resulted in the release of infectious WNV. The growth rate and plaque size of the recombinant virus were almost identical to those of the parent WNV. Furthermore, chimeric WNV was produced by introducing the DNA fragment coding for the structural protein and replicon plasmid derived from various strains. Here, we report development of a novel system that will facilitate research into WNV infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Antiviral Activity of Nordihydroguaiaretic Acid and Its Derivative Tetra-O-Methyl Nordihydroguaiaretic Acid against West Nile Virus and Zika Virus.

    PubMed

    Merino-Ramos, Teresa; Jiménez de Oya, Nereida; Saiz, Juan-Carlos; Martín-Acebes, Miguel A

    2017-08-01

    Flaviviruses are positive-strand RNA viruses distributed all over the world that infect millions of people every year and for which no specific antiviral agents have been approved. These viruses include the mosquito-borne West Nile virus (WNV), which is responsible for outbreaks of meningitis and encephalitis. Considering that nordihydroguaiaretic acid (NDGA) has been previously shown to inhibit the multiplication of the related dengue virus and hepatitis C virus, we have evaluated the effect of NDGA, and its methylated derivative tetra- O -methyl nordihydroguaiaretic acid (M 4 N), on the infection of WNV. Both compounds inhibited the infection of WNV, likely by impairing viral replication. Since flavivirus multiplication is highly dependent on host cell lipid metabolism, the antiviral effect of NDGA has been previously related to its ability to disturb the lipid metabolism, probably by interfering with the sterol regulatory element-binding proteins (SREBP) pathway. Remarkably, we observed that other structurally unrelated inhibitors of the SREBP pathway, such as PF-429242 and fatostatin, also reduced WNV multiplication, supporting that the SREBP pathway may constitute a druggable target suitable for antiviral intervention against flavivirus infection. Moreover, treatment with NDGA, M 4 N, PF-429242, and fatostatin also inhibited the multiplication of the mosquito-borne flavivirus Zika virus (ZIKV), which has been recently associated with birth defects (microcephaly) and neurological disorders. Our results point to SREBP inhibitors, such as NDGA and M 4 N, as potential candidates for further antiviral development against medically relevant flaviviruses. Copyright © 2017 American Society for Microbiology.

  8. The evolution of virulence of West Nile virus in a mosquito vector: implications for arbovirus adaptation and evolution.

    PubMed

    Ciota, Alexander T; Ehrbar, Dylan J; Matacchiero, Amy C; Van Slyke, Greta A; Kramer, Laura D

    2013-03-20

    Virulence is often coupled with replicative fitness of viruses in vertebrate systems, yet the relationship between virulence and fitness of arthropod-borne viruses (arboviruses) in invertebrates has not been evaluated. Although the interactions between vector-borne pathogens and their invertebrate hosts have been characterized as being largely benign, some costs of arbovirus exposure have been identified for mosquitoes. The extent to which these costs may be strain-specific and the subsequent consequences of these interactions on vector and virus evolution has not been adequately explored. Using West Nile virus (WNV) and Culex pipiens mosquitoes, we tested the hypothesis that intrahost fitness is correlated with virulence in mosquitoes by evaluating life history traits following exposure to either non-infectious bloodmeals or bloodmeals containing wildtype (WNV WT) or the high fitness, mosquito-adapted strain, WNV MP20 derived from WNV WT. Our results demonstrate strain-specific effects on mosquito survival, fecundity, and blood feeding behavior. Specifically, both resistance to and infection with WNV MP20, but not WNV WT, decreased survival of Cx. pipiens and altered fecundity and bloodfeeding such that early egg output was enhanced at a later cost. As predicted by the trade-off hypothesis of virulence, costs of infection with WNV MP20 in terms of survival were directly correlated to viral load, yet resistance to infection with this virulent strain was equally costly. Taken together, these results demonstrate that WNV MP20 infection decreases the transmission potential of Cx. pipiens populations despite the increased intrahost fitness of this strain, indicating that a virulence-transmission trade-off in invertebrates could contribute significantly to the adaptive and evolutionary constraint of arboviruses.

  9. Conservation and variability of West Nile virus proteins.

    PubMed

    Koo, Qi Ying; Khan, Asif M; Jung, Keun-Ok; Ramdas, Shweta; Miotto, Olivo; Tan, Tin Wee; Brusic, Vladimir; Salmon, Jerome; August, J Thomas

    2009-01-01

    West Nile virus (WNV) has emerged globally as an increasingly important pathogen for humans and domestic animals. Studies of the evolutionary diversity of the virus over its known history will help to elucidate conserved sites, and characterize their correspondence to other pathogens and their relevance to the immune system. We describe a large-scale analysis of the entire WNV proteome, aimed at identifying and characterizing evolutionarily conserved amino acid sequences. This study, which used 2,746 WNV protein sequences collected from the NCBI GenPept database, focused on analysis of peptides of length 9 amino acids or more, which are immunologically relevant as potential T-cell epitopes. Entropy-based analysis of the diversity of WNV sequences, revealed the presence of numerous evolutionarily stable nonamer positions across the proteome (entropy value of < or = 1). The representation (frequency) of nonamers variant to the predominant peptide at these stable positions was, generally, low (< or = 10% of the WNV sequences analyzed). Eighty-eight fragments of length 9-29 amino acids, representing approximately 34% of the WNV polyprotein length, were identified to be identical and evolutionarily stable in all analyzed WNV sequences. Of the 88 completely conserved sequences, 67 are also present in other flaviviruses, and several have been associated with the functional and structural properties of viral proteins. Immunoinformatic analysis revealed that the majority (78/88) of conserved sequences are potentially immunogenic, while 44 contained experimentally confirmed human T-cell epitopes. This study identified a comprehensive catalogue of completely conserved WNV sequences, many of which are shared by other flaviviruses, and majority are potential epitopes. The complete conservation of these immunologically relevant sequences through the entire recorded WNV history suggests they will be valuable as components of peptide-specific vaccines or other therapeutic

  10. West Nile virus surveillance in Europe: moving towards an integrated animal-human-vector approach.

    PubMed

    Gossner, Céline M; Marrama, Laurence; Carson, Marianne; Allerberger, Franz; Calistri, Paolo; Dilaveris, Dimitrios; Lecollinet, Sylvie; Morgan, Dilys; Nowotny, Norbert; Paty, Marie-Claire; Pervanidou, Danai; Rizzo, Caterina; Roberts, Helen; Schmoll, Friedrich; Van Bortel, Wim; Gervelmeyer, Andrea

    2017-05-04

    This article uses the experience of five European countries to review the integrated approaches (human, animal and vector) for surveillance and monitoring of West Nile virus (WNV) at national and European levels. The epidemiological situation of West Nile fever in Europe is heterogeneous. No model of surveillance and monitoring fits all, hence this article merely encourages countries to implement the integrated approach that meets their needs. Integration of surveillance and monitoring activities conducted by the public health authorities, the animal health authorities and the authorities in charge of vector surveillance and control should improve efficiency and save resources by implementing targeted measures. The creation of a formal interagency working group is identified as a crucial step towards integration. Blood safety is a key incentive for public health authorities to allocate sufficient resources for WNV surveillance, while the facts that an effective vaccine is available for horses and that most infected animals remain asymptomatic make the disease a lesser priority for animal health authorities. The examples described here can support other European countries wishing to strengthen their WNV surveillance or preparedness, and also serve as a model for surveillance and monitoring of other (vector-borne) zoonotic infections. This article is copyright of The Authors, 2017.

  11. Spatial spreading model and dynamics of West Nile virus in birds and mosquitoes with free boundary.

    PubMed

    Lin, Zhigui; Zhu, Huaiping

    2017-12-01

    In this paper, a reaction-diffusion system is proposed to model the spatial spreading of West Nile virus in vector mosquitoes and host birds in North America. Transmission dynamics are based on a simplified model involving mosquitoes and birds, and the free boundary is introduced to model and explore the expanding front of the infected region. The spatial-temporal risk index [Formula: see text], which involves regional characteristic and time, is defined for the simplified reaction-diffusion model with the free boundary to compare with other related threshold values, including the usual basic reproduction number [Formula: see text]. Sufficient conditions for the virus to vanish or to spread are given. Our results suggest that the virus will be in a scenario of vanishing if [Formula: see text], and will spread to the whole region if [Formula: see text] for some [Formula: see text], while if [Formula: see text], the spreading or vanishing of the virus depends on the initial number of infected individuals, the area of the infected region, the diffusion rate and other factors. Moreover, some remarks on the basic reproduction numbers and the spreading speeds are presented and compared.

  12. Seroprevalence of West Nile and Usutu viruses in military working horses and dogs, Morocco, 2012: dog as an alternative WNV sentinel species?

    PubMed

    Durand, B; Haskouri, H; Lowenski, S; Vachiery, N; Beck, C; Lecollinet, S

    2016-07-01

    A serosurvey of 349 military working horses and 231 military working dogs was conducted in ten sites in Morocco in 2012. This survey revealed a high level of exposure of these animals to flaviviruses: seroprevalence rates of 60% in horses and of 62% in dogs were observed using a competitive West Nile virus (WNV) enzyme-linked immunosorbent assay (cELISA). Seroneutralization test results showed that the majority of cELISA-positive results were due to exposure to WNV. Further assays conducted in vaccinated horses with a DIVA (Differentiating Infected from Vaccinated Animals) test indicated that anti-WNV antibodies had been stimulated through WNV natural infection. Moreover, in both species, seroneutralization tests suggested an exposure to Usutu virus (USUV). Data analysis did not show any significant difference of cELISA seropositivity risk between horses and dogs. Dogs may thus represent an interesting alternative to equines for the serological surveillance of WNV or USUV circulation, especially in areas where equine vaccination precludes passive surveillance (based on the detection of West Nile fever cases) in horses.

  13. Creating a disease risk map for West Nile virus for surveillance in Central Texas using a Geographic Information System and Remote Sensing technologies

    USDA-ARS?s Scientific Manuscript database

    Following the discovery of the West Nile virus (WNv) in Brazos County, TX in 2002, mosquito research personnel at Texas A&M University established a routine WNv mosquito vector surveillance program in the county. In 2004, a map of Brazos County was created depicting areas that had a heightened leve...

  14. The Zika Virus | NIH MedlinePlus the Magazine

    MedlinePlus

    ... member of the flavivirus family. Other flaviviruses include dengue, yellow fever, and West Nile virus. Like its ... grantees have long studied Zika relatives, such as dengue and West Nile virus. Those studies provide a ...

  15. Meteorological conditions associated with increased incidence of West Nile virus disease in the United States, 2004-2012.

    PubMed

    Hahn, Micah B; Monaghan, Andrew J; Hayden, Mary H; Eisen, Rebecca J; Delorey, Mark J; Lindsey, Nicole P; Nasci, Roger S; Fischer, Marc

    2015-05-01

    West Nile virus (WNV) is a leading cause of mosquito-borne disease in the United States. Annual seasonal outbreaks vary in size and location. Predicting where and when higher than normal WNV transmission will occur can help direct limited public health resources. We developed models for the contiguous United States to identify meteorological anomalies associated with above average incidence of WNV neuroinvasive disease from 2004 to 2012. We used county-level WNV data reported to ArboNET and meteorological data from the North American Land Data Assimilation System. As a result of geographic differences in WNV transmission, we divided the United States into East and West, and 10 climate regions. Above average annual temperature was associated with increased likelihood of higher than normal WNV disease incidence, nationally and in most regions. Lower than average annual total precipitation was associated with higher disease incidence in the eastern United States, but the opposite was true in most western regions. Although multiple factors influence WNV transmission, these findings show that anomalies in temperature and precipitation are associated with above average WNV disease incidence. Readily accessible meteorological data may be used to develop predictive models to forecast geographic areas with elevated WNV disease risk before the coming season. © The American Society of Tropical Medicine and Hygiene.

  16. Microarray hybridization for assessment of the genetic stability of chimeric West Nile/dengue 4 virus.

    PubMed

    Laassri, Majid; Bidzhieva, Bella; Speicher, James; Pletnev, Alexander G; Chumakov, Konstantin

    2011-05-01

    Genetic stability is an important characteristic of live viral vaccines because an accumulation of mutants can cause reversion to a virulent phenotype as well as a loss of immunogenic properties. This study was aimed at evaluating the genetic stability of a live attenuated West Nile (WN) virus vaccine candidate that was generated by replacing the pre-membrane and envelope protein genes of dengue 4 virus with those from WN. Chimeric virus was serially propagated in Vero, SH-SY5Y human neuroblastoma and HeLa cells and screened for point mutations using hybridization with microarrays of overlapping oligonucleotide probes covering the entire genome. The analysis revealed several spontaneous mutations that led to amino acid changes, most of which were located in the envelope (E) and non-structural NS4A, NS4B, and NS5 proteins. Viruses passaged in Vero and SH-SY5Y cells shared two common mutations: G(2337) C (Met(457) Ile) in the E gene and A(6751) G (Lys(125) Arg) in the NS4A gene. Quantitative assessment of the contents of these mutants in viral stocks indicated that they accumulated independently with different kinetics during propagation in cell cultures. Mutant viruses grew better in Vero cells compared to the parental virus, suggesting that they have a higher fitness. When tested in newborn mice, the cell culture-passaged viruses did not exhibit increased neurovirulence. The approach described in this article could be useful for monitoring the molecular consistency and quality control of vaccine strains. Copyright © 2011 Wiley-Liss, Inc.

  17. Microarray Hybridization for Assessment of the Genetic Stability of Chimeric West Nile/Dengue 4 Virus

    PubMed Central

    Laassri, Majid; Bidzhieva, Bella; Speicher, James; Pletnev, Alexander G.; Chumakov, Konstantin

    2012-01-01

    Genetic stability is an important characteristic of live viral vaccines because an accumulation of mutants can cause reversion to a virulent phenotype as well as a loss of immunogenic properties. This study was aimed at evaluating the genetic stability of a live attenuated West Nile (WN) virus vaccine candidate that was generated by replacing the pre-membrane and envelope protein genes of dengue 4 virus with those from WN. Chimeric virus was serially propagated in Vero, SH-SY5Y human neuroblastoma and HeLa cells and screened for point mutations using hybridization with microarrays of overlapping oligonucleotide probes covering the entire genome. The analysis revealed several spontaneous mutations that led to amino acid changes, most of which were located in the envelope (E) and non-structural NS4A, NS4B, and NS5 proteins. Viruses passaged in Vero and SH-SY5Y cells shared two common mutations: G2337C (Met457Ile) in the E gene and A6751G (Lys125Arg) in the NS4A gene. Quantitative assessment of the contents of these mutants in viral stocks indicated that they accumulated independently with different kinetics during propagation in cell cultures. Mutant viruses grew better in Vero cells compared to the parental virus, suggesting that they have a higher fitness. When tested in newborn mice, the cell culture-passaged viruses did not exhibit increased neurovirulence. The approach described in this paper could be useful for monitoring the molecular consistency and quality control of vaccine strains. PMID:21360544

  18. Correlation of West Nile Virus Incidence in Donated Blood with West Nile Neuroinvasive Disease Rates, United States, 2010-2012.

    PubMed

    Betsem, Edouard; Kaidarova, Zhanna; Stramer, Susan L; Shaz, Beth; Sayers, Merlyn; LeParc, German; Custer, Brian; Busch, Michael P; Murphy, Edward L

    2017-02-01

    Over the past decade, West Nile virus (WNV) has spread across the United States. We aggregated blood donor data from 2010-2012 and then calculated the incidence of WNV RNA-positive donations and compared the incidence with neuroinvasive disease (NID) case data from the ArboNET surveillance system. Of 10,107,853 donations, 640 were confirmed positive. The seasonal WNV incidence rate per 100,000 persons was 33.4 (95% CI 22-45) in 2010, 25.7 (95% CI 15-34) in 2011, and 119.9 (95% CI 98-141) in 2012. NID to blood donor ratios were 1 in 164 (95% CI 152-178) in 2010, 1 in 158 (95% CI 145-174) in 2011, and 1 in 131 (95% CI 127-136) in 2012. We updated estimates of the ratio of NID to WNV infection rates, demonstrating stable disease penetrance over the study period. Blood donor WNV RNA screening is a valuable public health tool for WNV surveillance.

  19. A Live Attenuated Chimeric West Nile Virus Vaccine, rWN/DEN4Δ30, Is Well Tolerated and Immunogenic in Flavivirus-Naive Older Adult Volunteers.

    PubMed

    Pierce, Kristen K; Whitehead, Stephen S; Kirkpatrick, Beth D; Grier, Palmtama L; Jarvis, Adrienne; Kenney, Heather; Carmolli, Marya P; Reynolds, Cynthia; Tibery, Cecilia M; Lovchik, Janece; Janiak, Anna; Luke, Catherine J; Durbin, Anna P; Pletnev, Alexander G

    2017-01-01

    West Nile virus (WNV) is a major cause of mosquito-borne illness in the United States. Human disease ranges from mild febrile illness to severe fatal neurologic infection. Adults aged >60 years are more susceptible to neuroinvasive disease accompanied by a high mortality rate or long-lasting neurologic sequelae. A chimeric live attenuated West Nile virus vaccine, rWN/DEN4Δ30, was shown to be safe and immunogenic in healthy adults aged 18-50 years. This study evaluated rWN/DEN4Δ30 in flavivirus-naive adults aged 50-65 years and found it to be safe and immunogenic. Outbreaks of WNV infection tend to be unpredictable, and a safe and effective vaccine will be an important public health tool. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  20. Asymmetric Weakness and West Nile Virus Infection.

    PubMed

    Kuo, Dick C; Bilal, Saadiyah; Koller, Paul

    2015-09-01

    Weakness is a common presentation in the emergency department (ED). Asymmetric weakness or weakness that appears not to follow an anatomical pattern is a less common occurrence. Acute flaccid paralysis with no signs of meningoencephalitis is one of the more uncommon presentations of West Nile virus (WNV). Patient may complain of an acute onset of severe weakness, or even paralysis, in one or multiple limbs with no sensory deficits. This weakness is caused by injury to the anterior horn cells of the spinal cord. We present a case of acute asymmetric flaccid paralysis with preserved sensory responses that was eventually diagnosed as neuroinvasive WNV infection. A 31-year-old male with no medical history presented with complaints of left lower and right upper extremity weakness. Computed tomography scan was negative and multiple other studies were performed in the ED. Eventually, he was admitted to the hospital and was found to have decreased motor amplitudes, severely reduced motor neuron recruitment, and denervation on electrodiagnostic study. Cerebrospinal fluid specimen tested positive for WNV immunoglobulin (Ig) G and IgM antibodies. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Acute asymmetric flaccid paralysis with no signs of viremia or meningoencephalitis is an unusual presentation of WNV infection. WNV should be included in the differential for patients with asymmetric weakness, especially in the summer months in areas with large mosquito populations. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Serological Survey of West Nile Virus in Domestic Animals from Northwest Senegal.

    PubMed

    Davoust, Bernard; Maquart, Marianne; Roqueplo, Cédric; Gravier, Patrick; Sambou, Masse; Mediannikov, Oleg; Leparc-Goffart, Isabelle

    2016-05-01

    In Africa, infection with West Nile virus (WNV) is frequent but almost always asymptomatic in humans and equids. The aim of this study was to identify whether any other domestic animal living in the same enzootic locality may be the sentinel of WNV circulation. In northwest Senegal, blood samples were collected from 283 adult domestic animals (136 sheep, 64 horses, 29 donkeys, 29 goats, 14 cattle, and 11 dogs), in three localities near Keur Momar Sarr. Each serum was tested for WNV immunoglobulin G using enzyme-linked immunosorbent assay. The prevalence among donkeys, horses, dogs, goats, cattle, and sheep was 86.2%, 68.7%, 27.3%, 6.9%, 0%, and 0%, respectively. This survey confirms that equids and dogs could be the best sentinel animals for surveillance of WNV. The ruminants do not play a role in WNV epidemiology.

  2. West Nile virus epizootics in the Camargue (France) in 2015 and reinforcement of surveillance and control networks.

    PubMed

    Bahuon, C; Marcillaud-Pitel, C; Bournez, L; Leblond, A; Beck, C; Hars, J; Leparc-Goffart, I; L'Ambert, G; Paty, M-C; Cavalerie, L; Daix, C; Tritz, P; Durand, B; Zientara, S; Lecollinet, S

    2016-12-01

    West Nile virus (WNV) infection is a non-contagious disease mainly transmitted by the bites of infected mosquitoes from the genus Culex. The virus is maintained in a mosquito-bird-mosquito cycle, and can accidentally be transmitted to mammalian hosts. Among mammalian hosts, equines and humans are the most sensitive to WNV infection and can develop severe meningoencephalitis. As WNV infections are zoonotic and can be severe in humans and equines, West Nile fever is considered to be a public and animal health concern. After a silent period of almost ten years, WNV re-emerged in France at the periphery of the Camargue area during the summer of 2015, underlining the fact that the Camargue area creates favourable conditions for WNV emergence and amplification in France. The French Network for Epidemiological Surveillance of Equine Diseases (Réseau d'Épidémio-Surveillance en Pathologie Équine [RESPE]) facilitated the early detection of WNV cases in horses. In total, 49 horses were found to be infected; among them, 44 presented clinical signs, 41 with meningoencephalitis and three with hyperthermia only. Six horses among the 41 with nervous symptoms died from the disease or were euthanised (a case fatality rate of 14.6%). The authors describe the characteristics of the 2015 WNV epizootics, the early detection of the first WNV equine cases via the RESPE network and the coordination of WNV surveillance in France. © OIE (World Organisation for Animal Health), 2016.

  3. Plasticity of a critical antigenic determinant in the West Nile virus NY99 envelope protein domain III.

    PubMed

    Plante, Jessica A; Torres, Maricela; Huang, Claire Y-H; Beasley, David W C

    2016-09-01

    West Nile virus (WNV) is a mosquito-borne flavivirus that causes febrile illness, encephalitis, and occasionally death in humans. The envelope protein is the main component of the WNV virion surface, and domain III of the envelope protein (EIII) is both a putative receptor binding domain and a target of highly specific, potently neutralizing antibodies. Envelope E-332 (E-332) is known to have naturally occurring variation and to be a key determinant of neutralization for anti-EIII antibodies. A panel of viruses containing all possible amino acid substitutions at E-332 was constructed. E-332 was found to be highly tolerant of mutation, and almost all of these changes had large impacts on antigenicity of EIII but only limited effects on growth or virulence phenotypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. West Nile virus lineage 2 infection in a blood donor from Vienna, Austria, August 2014.

    PubMed

    Jungbauer, C; Hourfar, M K; Stiasny, K; Aberle, S W; Cadar, D; Schmidt-Chanasit, J; Mayr, W R

    2015-03-01

    Eastern Austria is neighbouring regions with ongoing West Nile virus (WNV) transmissions. Three human WNV infections had been diagnosed during the past decade in Austria. The Austrian Red Cross Blood Service (ARC-BS) started a first voluntary screening for WNV in blood donors from Eastern Austria by Nucleic Acid Testing (NAT) in June 2014. This is also the most extensive WNV surveillance programme in humans in Austria so far. In August 2014, one autochthonous WNV infection was detected in a blood donor from Vienna. By now, one in 67,800 whole blood donations was found to be positive for WNV RNA. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. DNA-immunisation with dengue virus E protein domains I/II, but not domain III, enhances Zika, West Nile and Yellow Fever virus infection.

    PubMed

    Slon Campos, Jose L; Poggianella, Monica; Marchese, Sara; Mossenta, Monica; Rana, Jyoti; Arnoldi, Francesca; Bestagno, Marco; Burrone, Oscar R

    2017-01-01

    Dengue virus (DENV), the causative agent of dengue disease, is among the most important mosquito-borne pathogens worldwide. DENV is composed of four closely related serotypes and belongs to the Flaviviridae family alongside other important arthropod-borne viral pathogens such as Zika virus (ZIKV), West Nile virus (WNV) and Yellow Fever virus (YFV). After infection, the antibody response is mostly directed to the viral E glycoprotein which is composed of three structural domains named DI, DII and DIII that share variable degrees of homology among different viruses. Recent evidence supports a close serological interaction between ZIKV and DENV. The possibility of worse clinical outcomes as a consequence of antibody-dependent enhancement of infection (ADE) due to cross-reactive antibodies with poor neutralisation activity is a matter of concern. We tested polyclonal sera from groups of female Balb/C mice vaccinated with DNA constructs expressing DI/DII, DIII or the whole sE from different DENV serotypes and compared their activity in terms of cross-reactivity, neutralisation of virus infection and ADE. Our results indicate that the polyclonal antibody responses against the whole sE protein are highly cross-reactive with strong ADE and poor neutralisation activities due to DI/DII immunodominance. Conversely, anti-DIII polyclonal antibodies are type-specific, with no ADE towards ZIKV, WNV and YFV, and strong neutralisation activity restricted only to DENV.

  6. West Nile Virus Outbreak in North American Owls, Ontario, 2002

    PubMed Central

    Barker, Ian K.; Lindsay, Robbin; Dibernardo, Antonia; McKeever, Katherine; Hunter, Bruce

    2004-01-01

    From July to September 2002, an outbreak of West Nile virus (WNV) caused a high number of deaths in captive owls at the Owl Foundation, Vineland, Ontario, Canada. Peak death rates occurred in mid-August, and the epidemiologic curve resembled that of corvids in the surrounding Niagara region. The outbreak occurred in the midst of a louse fly (Icosta americana, family Hippoboscidae) infestation. Of the flies tested, 16 (88.9 %) of 18 contained WNV RNA. Species with northern native breeding range and birds >1 year of age were at significantly higher risk for WNV-related deaths. Species with northern native breeding range and of medium-to-large body size were at significantly higher risk for exposure to WNV. Taxonomic relations (at the subfamily level) did not significantly affect exposure to WNV or WNV-related deaths. Northern native breeding range and medium-to-large body size were associated with earlier death within the outbreak period. Of the survivors, 69 (75.8 %) of 91 were seropositive for WNV. PMID:15663850

  7. Ecologic Factors Associated with West Nile Virus Transmission, Northeastern United States

    PubMed Central

    Brown, Heidi E.; Childs, James E.; Diuk-Wasser, Maria A.

    2008-01-01

    Since 1999, West Nile virus (WNV) disease has affected the northeastern United States. To describe the spatial epidemiology and identify risk factors for disease incidence, we analyzed 8 years (1999–2006) of county-based human WNV disease surveillance data. Among the 56.6 million residents in 8 northeastern states sharing primary enzootic vectors, we found 977 cases. We controlled for population density and potential bias from surveillance and spatial proximity. Analyses demonstrated significant spatial spreading from 1999 through 2004 (p<0.01, r2 = 0.16). A significant trend was apparent among increasingly urban counties; county quartiles with the least (<38%) forest cover had 4.4-fold greater odds (95% confidence interval [CI] 1.4–13.2, p = 0.01) of having above-median disease incidence (>0.75 cases/100,000 residents) than counties with the most (>70%) forest cover. These results quantify urbanization as a risk factor for WNV disease incidence and are consistent with knowledge of vector species in this area. PMID:18826816

  8. Plant-made vaccines against West Nile virus are potent, safe, and economically feasible.

    PubMed

    Chen, Qiang

    2015-05-01

    The threat of West Nile virus (WNV) epidemics with increasingly severe neuroinvasive infections demands the development and licensing of effective vaccines. To date, vaccine candidates based on inactivated, live-attenuated, or chimeric virus, and viral DNA and WNV protein subunits have been developed. Some have been approved for veterinary use or are under clinical investigation, yet no vaccine has been licensed for human use. Reaching the milestone of a commercialized human vaccine, however, may largely depend on the economics of vaccine production. Analysis suggests that currently only novel low-cost production technologies would allow vaccination to outcompete the cost of surveillance and clinical treatment. Here, we review progress using plants to address the economic challenges of WNV vaccine production. The advantages of plants as hosts for vaccine production in cost, speed and scalability, especially those of viral vector-based transient expression systems, are discussed. The progress in developing WNV subunit vaccines in plants is reviewed within the context of their expression, characterization, downstream processing, and immunogenicity in animal models. The development of vaccines based on enveloped and non-enveloped virus-like particles is also discussed. These advancements suggest that plants may provide a production platform that offers potent, safe and affordable human vaccines against WNV. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Lineage 2 west nile virus as cause of fatal neurologic disease in horses, South Africa.

    PubMed

    Venter, Marietjie; Human, Stacey; Zaayman, Dewald; Gerdes, Gertruida H; Williams, June; Steyl, Johan; Leman, Patricia A; Paweska, Janusz Tadeusz; Setzkorn, Hildegard; Rous, Gavin; Murray, Sue; Parker, Rissa; Donnellan, Cynthia; Swanepoel, Robert

    2009-06-01

    Serologic evidence suggests that West Nile virus (WNV) is widely distributed in horses in southern Africa. However, because few neurologic cases have been reported, endemic lineage 2 strains were postulated to be nonpathogenic in horses. Recent evidence suggests that highly neuroinvasive lineage 2 strains exist in humans and mice. To determine whether neurologic cases are being missed in South Africa, we tested 80 serum or brain specimens from horses with unexplained fever (n = 48) and/or neurologic signs (n = 32) for WNV. From March 2007 through June 2008, using reverse transcription-PCR (RT-PCR) and immunoglobulin (Ig) M ELISA, we found WNV RNA or IgM in 7/32 horses with acute neurologic disease; 5 horses died or were euthanized. In 5/7 horses, no other pathogen was detected. DNA sequencing for all 5 RT-PCR-positive cases showed the virus belonged to lineage 2. WNV lineage 2 may cause neurologic disease in horses in South Africa.

  10. Susceptibility of Carrion Crows to Experimental Infection with Lineage 1 and 2 West Nile Viruses.

    PubMed

    Lim, Stephanie M; Brault, Aaron C; van Amerongen, Geert; Bosco-Lauth, Angela M; Romo, Hannah; Sewbalaksing, Varsha D; Bowen, Richard A; Osterhaus, Albert D M E; Koraka, Penelope; Martina, Byron E E

    2015-08-01

    West Nile virus (WNV) outbreaks in North America have been characterized by substantial die-offs of American crows (Corvus brachyrhynchos). In contrast, a low incidence of bird deaths has been observed during WNV epidemic activity in Europe. To examine the susceptibility of the western European counterpart of American crows, we inoculated carrion crows (Corvus corone) with WNV strains isolated in Greece (Gr-10), Italy (FIN and Ita09), and Hungary (578/10) and with the highly virulent North American genotype strain (NY99). We also inoculated American crows with a selection of these strains to examine the strains' virulence in a highly susceptible bird species. Infection with all strains, except WNV FIN, resulted in high rates of death and high-level viremia in both bird species and virus dissemination to several organs. These results suggest that carrion crows are highly susceptible to WNV and may potentially be useful as part of dead bird surveillance for early warning of WNV activity in Europe.

  11. Susceptibility of Carrion Crows to Experimental Infection with Lineage 1 and 2 West Nile Viruses

    PubMed Central

    Lim, Stephanie M.; Brault, Aaron C.; van Amerongen, Geert; Bosco-Lauth, Angela M.; Romo, Hannah; Sewbalaksing, Varsha D.; Bowen, Richard A.; Osterhaus, Albert D.M.E.; Koraka, Penelope

    2015-01-01

    West Nile virus (WNV) outbreaks in North America have been characterized by substantial die-offs of American crows (Corvus brachyrhynchos). In contrast, a low incidence of bird deaths has been observed during WNV epidemic activity in Europe. To examine the susceptibility of the western European counterpart of American crows, we inoculated carrion crows (Corvus corone) with WNV strains isolated in Greece (Gr-10), Italy (FIN and Ita09), and Hungary (578/10) and with the highly virulent North American genotype strain (NY99). We also inoculated American crows with a selection of these strains to examine the strains’ virulence in a highly susceptible bird species. Infection with all strains, except WNV FIN, resulted in high rates of death and high-level viremia in both bird species and virus dissemination to several organs. These results suggest that carrion crows are highly susceptible to WNV and may potentially be useful as part of dead bird surveillance for early warning of WNV activity in Europe. PMID:26197093

  12. Thermal preference predicts animal personality in Nile tilapia Oreochromis niloticus.

    PubMed

    Cerqueira, Marco; Rey, Sonia; Silva, Tome; Featherstone, Zoe; Crumlish, Margaret; MacKenzie, Simon

    2016-09-01

    Environmental temperature gradients provide habitat structure in which fish orientate and individual thermal choice may reflect an essential integrated response to the environment. The use of subtle thermal gradients likely impacts upon specific physiological and behavioural processes reflected as a suite of traits described by animal personality. In this study, we examine the relationship between thermal choice, animal personality and the impact of infection upon this interaction. We predicted that thermal choice in Nile tilapia Oreochromis niloticus reflects distinct personality traits and that under a challenge individuals exhibit differential thermal distribution. Nile tilapia were screened following two different protocols: 1) a suite of individual behavioural tests to screen for personality and 2) thermal choice in a custom-built tank with a thermal gradient (TCH tank) ranging from 21 to 33 °C. A first set of fish were screened for behaviour and then thermal preference, and a second set were tested in the opposite fashion: thermal then behaviour. The final thermal distribution of the fish after 48 h was assessed reflecting final thermal preferendum. Additionally, fish were then challenged using a bacterial Streptococcus iniae model infection to assess the behavioural fever response of proactive and reactive fish. Results showed that individuals with preference for higher temperatures were also classified as proactive with behavioural tests and reactive contemporaries chose significantly lower water temperatures. All groups exhibited behavioural fever recovering personality-specific thermal preferences after 5 days. Our results show that thermal preference can be used as a proxy to assess personality traits in Nile tilapia and it is a central factor to understand the adaptive meaning of animal personality within a population. Importantly, response to infection by expressing behavioural fever overrides personality-related thermal choice. © 2016 The Authors

  13. West Nile virus transmission: results from the integrated surveillance system in Italy, 2008 to 2015.

    PubMed

    Rizzo, Caterina; Napoli, Christian; Venturi, Giulietta; Pupella, Simonetta; Lombardini, Letizia; Calistri, Paolo; Monaco, Federica; Cagarelli, Roberto; Angelini, Paola; Bellini, Romeo; Tamba, Marco; Piatti, Alessandra; Russo, Francesca; Palù, Giorgio; Chiari, Mario; Lavazza, Antonio; Bella, Antonino

    2016-09-15

    In Italy a national Plan for the surveillance of imported and autochthonous human vector-borne diseases (chikungunya, dengue, Zika virus disease and West Nile virus (WNV) disease) that integrates human and veterinary (animals and vectors) surveillance, is issued and revised annually according with the observed epidemiological changes. Here we describe results of the WNV integrated veterinary and human surveillance systems in Italy from 2008 to 2015. A real time data exchange protocol is in place between the surveillance systems to rapidly identify occurrence of human and animal cases and to define and update the map of affected areas i.e. provinces during the vector activity period from June to October. WNV continues to cause severe illnesses in Italy during every transmission season, albeit cases are sporadic and the epidemiology varies by virus lineage and geographic area. The integration of surveillance activities and a multidisciplinary approach made it possible and have been fundamental in supporting implementation of and/or strengthening preventive measures aimed at reducing the risk of transmission of WNV trough blood, tissues and organ donation and to implementing further measures for vector control. This article is copyright of The Authors, 2016.

  14. Naturally induced humoral immunity to West Nile virus infection in raptors.

    PubMed

    Nemeth, Nicole M; Kratz, Gail E; Bates, Rebecca; Scherpelz, Judy A; Bowen, Richard A; Komar, Nicholas

    2008-09-01

    West Nile virus (WNV) infection can be fatal to many bird species, including numerous raptors, though population- and ecosystem-level impacts following introduction of the virus to North America have been difficult to document. Raptors occupy a diverse array of habitats worldwide and are important to ecosystems for their role as opportunistic predators. We documented initial (primary) WNV infection and then regularly measured WNV-specific neutralizing antibody titers in 16 resident raptors of seven species, plus one turkey vulture. Most individuals were initially infected and seroconverted between July and September of 2003, though three birds remained seronegative until summer 2006. Many of these birds became clinically ill upon primary infection, with clinical signs ranging from loss of appetite to moderate neurological disease. Naturally induced WNV neutralizing antibody titers remained essentially unchanged in some birds, while eight individuals experienced secondary rises in titer presumably due to additional exposures at 1, 2, or 3 years following primary infection. No birds experienced clinical signs surrounding or following the time of secondary exposure, and therefore antibodies were considered protective. Results of this study have implications for transmission dynamics of WNV and health of raptor populations, as well as the interpretation of serologic data from free-ranging and captive birds. Antibodies in raptors surviving WNV may persist for multiple years and protect against potential adverse effects of subsequent exposures.

  15. The virology, epidemiology, and clinical impact of West Nile virus: a decade of advancements in research since its introduction into the Western Hemisphere.

    PubMed

    Murray, K O; Walker, C; Gould, E

    2011-06-01

    West Nile virus (WNV) is now endemic in the USA. After the widespread surge of virus activity across the USA, research has flourished, and our knowledge base has significantly expanded over the past 10 years since WNV was first recognized in New York City. This article provides a review of the virology of WNV, history, epidemiology, clinical features, pathology of infection, the innate and adaptive immune response, host risk factors for developing severe disease, clinical sequelae following severe disease, chronic infection, and the future of prevention.

  16. Predicting outbreaks: a spatial risk assessment of West Nile virus in British Columbia

    PubMed Central

    Tachiiri, Kaoru; Klinkenberg, Brian; Mak, Sunny; Kazmi, Jamil

    2006-01-01

    Background West Nile virus (WNv) has recently emerged as a health threat to the North American population. After the initial disease outbreak in New York City in 1999, WNv has spread widely and quickly across North America to every contiguous American state and Canadian province, with the exceptions of British Columbia (BC), Prince Edward Island and Newfoundland. In this study we develop models of mosquito population dynamics for Culex tarsalis and C. pipiens, and create a spatial risk assessment of WNv prior to its arrival in BC by creating a raster-based mosquito abundance model using basic geographic and temperature data. Among the parameters included in the model are spatial factors determined from the locations of BC Centre for Disease Control mosquito traps (e.g., distance of the trap from the closest wetland or lake), while other parameters were obtained from the literature. Factors not considered in the current assessment but which could influence the results are also discussed. Results Since the model performs much better for C. tarsalis than for C. pipiens, the risk assessment is carried out using the output of C. tarsalis model. The result of the spatially-explicit mosquito abundance model indicates that the Okanagan Valley, the Thompson Region, Greater Vancouver, the Fraser Valley and southeastern Vancouver Island have the highest potential abundance of the mosquitoes. After including human population data, Greater Vancouver, due to its high population density, increases in significance relative to the other areas. Conclusion Creating a raster-based mosquito abundance map enabled us to quantitatively evaluate WNv risk throughout BC and to identify the areas of greatest potential risk, prior to WNv introduction. In producing the map important gaps in our knowledge related to mosquito ecology in BC were identified, as well, it became evident that increased efforts in bird and mosquito surveillance are required if more accurate models and maps are to be

  17. Detection of West Nile Virus and other common equine viruses in three locations from the Leeward Islands, West Indies.

    PubMed

    Bolfa, Pompei; Jeon, Isaac; Loftis, Amanda; Leslie, Teresa; Marchi, Silvia; Sithole, Fortune; Beck, Cecile; Lecollinet, Sylvie; Zientara, Stephan; Hans, Aymeric; Issel, Charles J

    2017-10-01

    Equines in the West Indies are used for recreational purposes, tourism industry, racing and agriculture or can be found in feral populations. Little is known in the Caribbean basin about the prevalence of some major equine infectious diseases, some with zoonotic potential, listed as reportable by the OIE. Our objective was to study the prevalence of antibodies for West Nile Virus (WNV), Equine Herpes Virus-1 and 4 (EHV-1 and EHV-4), Equine Influenza (EI), Equine Viral Arteritis (EVA) and Equine Infectious Anemia Virus (EIAV) using a retrospective serological convenience study. We used 180 equine serum samples, 140 from horses and 40 from donkeys in St. Kitts, Nevis, and Sint Eustatius, collected between 2006 and 2015 that were tested with ELISA kits and virus neutralization (for WNV and EVA). Combining ELISA with virus neutralization testing, 25 (13.8%) equine sera were WNV positive (a mixture of indigenous and imported equines) and 3 sera (1.6%) showed doubtful results. For EHV-1, 41 equines (23.7%), mean age 6.7 years, were seropositive. For EHV-4, 138 equines were found seropositive (82.8%), mean age 6.3 years. For EI, 49 equines (27.2%), mean age 7.5 years, were seropositive on ELISA, some previously vaccinated horses. No antibodies against EAV were found on virus neutralization testing, although one animal (0.6%), was EAV positive on ELISA. All samples were EIAV negative. The seroprevalence for EHV-1 and EHV-4 is similar to other parts of the world. For the first time in the study location serologic evidence of antibodies against WNV and EI is reported. This was found in both indigenous and imported animals, highlighting the need for developing proper surveillance plans based on complementary methods of virus detection. Further studies will be needed to define the prevalence, rates of transmission, characterize local virus strains, and study their impact on these populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Potential Reservoir and Associated Factors for West Nile Virus in Three Distinct Climatological Zones.

    PubMed

    DeCarlo, Christine; Omar, Anwar H; Haroun, Mohammod I; Bigler, Laura; Bin Rais, Mohamad N; Abu, Jalila; Omar, Abdul Rahman; Mohammed, Hussni O

    2017-10-01

    West Nile virus (WNV) is a zoonotic single-strand RNA arbovirus (family Flaviviridae: Flavivirus), transmitted among avian hosts in enzootic cycles by a mosquito vector. The virus has a significant disease effect on humans and equines when it bridges into a cycle with various sequelae with epidemic potential. This study was carried out to identify the potential spectrum of WNV hosts in three geographic areas with climatologically distinct features: Malaysia, Qatar, and the United States of America (U.S.). Serum samples were collected from avian and mammal species suspected to be reservoirs for the virus at these areas in a cross-sectional epidemiologic study. The samples were tested for the presence of antibodies against the virus using an enzyme-linked immunosorbent assay. Data on putative risk factors were also collected and analyzed for significance of association with seropositivity using the logistic regression analysis. Among the tested avian and mammalian species, raccoons had the highest seroconversion rate (54%) followed by crows (30%), horses (27%), camels (10%), other avian species (7%), and canine species (3%). It was almost twice as likely to detect seroconversion among these mammalian and avian species in the fall in comparison to other seasons of the year. Only mammalian and avian species and seasons of the year were significantly associated with the likelihood of seroconversion to WNV when we controlled for other factors in the multivariate analysis. Our data from the U.S. showed that raccoons and camels are susceptible to infection by the virus and may play a role in the perpetuation of endemic foci for the disease.

  19. Prediction of future climate change for the Blue Nile, using a nested Regional Climate Model

    NASA Astrophysics Data System (ADS)

    Soliman, E.; Jeuland, M.

    2009-04-01

    Although the Nile River Basin is rich in natural resources, it faces many challenges. Rainfall is highly variable across the region, on both seasonal and inter-annual scales. This variability makes the region vulnerable to droughts and floods. Many development projects involving Nile waters are currently underway, or being studied. These projects will lead to land-use patterns changes and water distribution and availability. It is thus important to assess the effects of a) these projects and b) evolving water resource management and policies, on regional hydrological processes. This paper seeks to establish a basis for evaluation of such impacts within the Blue Nile River sub-basin, using the RegCM3 Regional Climate Model to simulate interactions between the land surface and climatic processes. We first present results from application of this RCM model nested with downscaled outputs obtained from the ECHAM5/MPI-OM1 transient simulations for the 20th Century. We then investigate changes associated with mid-21st century emissions forcing of the SRES A1B scenario. The results obtained from the climate model are then fed as inputs to the Nile Forecast System (NFS), a hydrologic distributed rainfall runoff model of the Nile Basin, The interaction between climatic and hydrological processes on the land surface has been fully coupled. Rainfall patterns and evaporation rates have been generated using RegCM3, and the resulting runoff and Blue Nile streamflow patterns have been simulated using the NFS. This paper compares the results obtained from the RegCM3 climate model with observational datasets for precipitation and temperature from the Climate Research Unit (UK) and the NASA Goddard Space Flight Center GPCP (USA) for 1985-2000. The validity of the streamflow predictions from the NFS is assessed using historical gauge records. Finally, we present results from modeling of the A1B emissions scenario of the IPCC for the years 2034-2055. Our results indicate that future

  20. Emergency department management of mosquito-borne illness: malaria, dengue, and West Nile virus.

    PubMed

    Caraballo, Hector; King, Kevin

    2014-05-01

    Up to 700 million people are infected and more than a million die each year from mosquito-borne illness. While the vast majority of cases occur in endemic tropical and subtropical regions, international travel and migration patterns have increased their prevalence in North America. This review discusses the diagnosis and treatment of the 3 most common mosquito-borne illnesses seen in the United States: Plasmodium falciparum malaria, dengue, and West Nile virus. With no pathognomonic findings, it is critical that emergency clinicians in nonendemic areas maintain a high index of suspicion, conduct a thorough history/travel history, and interpret indirect findings to initiate prompt and appropriate treatment. This review gathers the best evidence from international public health resources, surveillance studies, guidelines, and academic research to give emergency clinicians tools to combat these potentially lethal infections.

  1. Serologic evidence of West Nile Virus infection in birds, Tamaulipas State, México.

    PubMed

    Fernández-Salas, Ildefonso; Contreras-Cordero, Juan F; Blitvich, Bradley J; González-Rojas, José I; Cavazos-Alvarez, Amanda; Marlenee, Nicole L; Elizondo-Quiroga, Armando; Loroño-Pino, María A; Gubler, Duane J; Cropp, Bruce C; Calisher, Charles H; Beaty, Barry J

    2003-01-01

    Following the introduction of West Nile virus (WNV) into North America in 1999, surveillance for WNV in migratory and resident birds was established in Tamaulipas State, northern México in December 2001. Overall, 796 birds representing 70 species and 10 orders were captured and assayed for antibodies to WNV. Nine birds had flavivirus-specific antibodies by epitope-blocking enzyme-linked immunosorbent assay; four were confirmed to have antibody to WNV by plaque reduction neutralization test. The WNV-infected birds were a house wren, mourning dove, verdin and Bewick's wren. The house wren is a migratory species; the other WNV-infected birds are presumably residents. The WNV-infected birds were all captured in March 2003. These data provide the first indirect evidence of WNV transmission among birds in northern México.

  2. A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death.

    PubMed

    Ma, Hongming; Dang, Ying; Wu, Yonggan; Jia, Gengxiang; Anaya, Edgar; Zhang, Junli; Abraham, Sojan; Choi, Jang-Gi; Shi, Guojun; Qi, Ling; Manjunath, N; Wu, Haoquan

    2015-07-28

    West Nile virus (WNV) causes an acute neurological infection attended by massive neuronal cell death. However, the mechanism(s) behind the virus-induced cell death is poorly understood. Using a library containing 77,406 sgRNAs targeting 20,121 genes, we performed a genome-wide screen followed by a second screen with a sub-library. Among the genes identified, seven genes, EMC2, EMC3, SEL1L, DERL2, UBE2G2, UBE2J1, and HRD1, stood out as having the strongest phenotype, whose knockout conferred strong protection against WNV-induced cell death with two different WNV strains and in three cell lines. Interestingly, knockout of these genes did not block WNV replication. Thus, these appear to be essential genes that link WNV replication to downstream cell death pathway(s). In addition, the fact that all of these genes belong to the ER-associated protein degradation (ERAD) pathway suggests that this might be the primary driver of WNV-induced cell death. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Enhanced production and immunological characterization of recombinant West Nile virus envelope domain III protein.

    PubMed

    Tripathi, Nagesh K; Karothia, Divyanshi; Shrivastava, Ambuj; Banger, Swati; Kumar, Jyoti S

    2018-05-13

    West Nile virus (WNV) is an emerging mosquito-borne virus which is responsible for severe and fatal encephalitis in humans and for which there is no licensed vaccine or therapeutic available to prevent infection. The envelope domain III protein (EDIII) of WNV was over-expressed in Escherichia coli and purified using a two-step chromatography process which included immobilized metal affinity chromatography and ion exchange chromatography. E. coli cells were grown in a bioreactor to high density using batch and fed-batch cultivation. Wet biomass obtained after batch and fed-batch cultivation processes was 11.2 g and 84 g/L of culture respectively. Protein yield after affinity purification was 5.76 mg and 5.81 mg/g wet cell weight after batch and fed-batch processes respectively. The purified WNV EDIII elicited specific antibodies in rabbits, confirming its immunogenicity. Moreover, the antibodies were able to neutralize WNV in vitro. These results established that the refolded and purified WNV EDIII could be a potential vaccine candidate. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Tripeptide inhibitors of dengue and West Nile virus NS2B-NS3 protease.

    PubMed

    Schüller, Andreas; Yin, Zheng; Brian Chia, C S; Doan, Danny N P; Kim, Hyeong-Kyu; Shang, Luqing; Loh, Teck Peng; Hill, Jeffery; Vasudevan, Subhash G

    2011-10-01

    A series of tripeptide aldehyde inhibitors were synthesized and their inhibitory effect against dengue virus type 2 (DENV2) and West Nile virus (WNV) NS3 protease was evaluated side by side with the aim to discover potent flaviviral protease inhibitors and to examine differences in specificity of the two proteases. The synthesized inhibitors feature a varied N-terminal cap group and side chain modifications of a P2-lysine residue. In general a much stronger inhibitory effect of the tripeptide inhibitors was observed toward WNV protease. The inhibitory concentrations against DENV2 protease were in the micromolar range while they were submicromolar against WNV. The data suggest that a P2-arginine shifts the specificity toward DENV2 protease while WNV protease favors a lysine in the P2 position. Peptides with an extended P2-lysine failed to inhibit DENV2 protease suggesting a size-constrained S2 pocket. Our results generally encourage the investigation of di- and tripeptide aldehydes as inhibitors of DENV and WNV protease. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. NMR study of complexes between low molecular mass inhibitors and the West Nile virus NS2B-NS3 protease.

    PubMed

    Su, Xun-Cheng; Ozawa, Kiyoshi; Yagi, Hiromasa; Lim, Siew P; Wen, Daying; Ekonomiuk, Dariusz; Huang, Danzhi; Keller, Thomas H; Sonntag, Sebastian; Caflisch, Amedeo; Vasudevan, Subhash G; Otting, Gottfried

    2009-08-01

    The two-component NS2B-NS3 protease of West Nile virus is essential for its replication and presents an attractive target for drug development. Here, we describe protocols for the high-yield expression of stable isotope-labelled samples in vivo and in vitro. We also describe the use of NMR spectroscopy to determine the binding mode of new low molecular mass inhibitors of the West Nile virus NS2B-NS3 protease which were discovered using high-throughput in vitro screening. Binding to the substrate-binding sites S1 and S3 is confirmed by intermolecular NOEs and comparison with the binding mode of a previously identified low molecular mass inhibitor. Our results show that all these inhibitors act by occupying the substrate-binding site of the protease rather than by an allosteric mechanism. In addition, the NS2B polypeptide chain was found to be positioned near the substrate-binding site, as observed previously in crystal structures of the protease in complex with peptide inhibitors or bovine pancreatic trypsin inhibitor. This indicates that the new low molecular mass compounds, although inhibiting the protease, also promote the proteolytically active conformation of NS2B, which is very different from the crystal structure of the protein without inhibitor.

  6. New evidence for the potential role of Culex pipiens mosquitoes in the transmission cycle of West Nile virus in Tunisia.

    PubMed

    Krida, G; Rhim, A; Daaboub, J; Failloux, A-B; Bouattour, A

    2015-06-01

    Physiological and molecular characteristics of natural populations of Culex pipiens Linnaeus, 1758 (Diptera: Culicidae) were investigated to elucidate how this species is potentially involved in the transmission of West Nile virus in Tunisia. A total of 215 Cx. pipiens females from 11 breeding habitats were analysed in the laboratory to estimate autogeny and stenogamy rates. They were tested individually for the locus CQ11 to distinguish between the two Cx. pipiens forms, pipiens and molestus. All tested Cx. pipiens populations were stenogamous. Females from underground breeding sites were all autogeneous, whereas females from above-ground habitats were mostly anautogeneous. Of all the females tested, 59.7% were identified as pipiens, 22.4% as molestus, and 17.9% as hybrid pipiens/molestus. Furthermore, both Cx. pipiens forms and their hybrids were found to co-occur in sympatry in all sites. The results of this study represent the first evidence that both Cx. pipiens forms and their hybrids are present in Tunisia. Because hybrids able to act as bridge vectors are present in all studied habitats, Tunisia can be considered to have a high degree of receptivity for the establishment of West Nile virus zoonotic cycles. © 2015 The Royal Entomological Society.

  7. Regional and seasonal response of a West Nile virus vector to climate change.

    PubMed

    Morin, Cory W; Comrie, Andrew C

    2013-09-24

    Climate change will affect the abundance and seasonality of West Nile virus (WNV) vectors, altering the risk of virus transmission to humans. Using downscaled general circulation model output, we calculate a WNV vector's response to climate change across the southern United States using process-based modeling. In the eastern United States, Culex quinquefasciatus response to projected climate change displays a latitudinal and elevational gradient. Projected summer population depressions as a result of increased immature mortality and habitat drying are most severe in the south and almost absent further north; extended spring and fall survival is ubiquitous. Much of California also exhibits a bimodal pattern. Projected onset of mosquito season is delayed in the southwestern United States because of extremely dry and hot spring and summers; however, increased temperature and late summer and fall rains extend the mosquito season. These results are unique in being a broad-scale calculation of the projected impacts of climate change on a WNV vector. The results show that, despite projected widespread future warming, the future seasonal response of C. quinquefasciatus populations across the southern United States will not be homogeneous, and will depend on specific combinations of local and regional conditions.

  8. On the potential roles of ticks and migrating birds in the ecology of West Nile virus.

    PubMed

    Hagman, Karl; Barboutis, Christos; Ehrenborg, Christian; Fransson, Thord; Jaenson, Thomas G T; Lindgren, Per-Eric; Lundkvist, Ake; Nyström, Fredrik; Waldenström, Jonas; Salaneck, Erik

    2014-01-15

    Mosquitoes are the primary vectors of West Nile virus (WNV). Ticks have, however, been suggested to be potential reservoirs of WNV. In order to investigate their role in the spread of the virus, ticks, which had been collected from birds migrating northwards from Africa to Europe, were analyzed for the potential presence of WNV-RNA. On the Mediterranean islands Capri and Antikythira a total of 14,824 birds were captured and investigated from which 747 ticks were collected. Most of the identified ticks (93%) were nymphs and larvae of Hyalomma marginatum sensu lato, most of which were or appear to be Hyalomma rufipes. Of these ticks 729 were individually screened for WNV-RNA. None of the ticks was found to be WNV positive. Thus, there was no evidence that Hyalomma marginatum s.l. ticks play a role in the spread of WNV from Africa to Europe.

  9. Flaviviruses, an expanding threat in public health: focus on Dengue, West Nile, and Japanese encephalitis virus

    PubMed Central

    Daep, Carlo Amorin; Muñoz-Jordán, Jorge L.; Eugenin, Eliseo Alberto

    2014-01-01

    The flaviviruses Dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors (Aedes and Culex sp), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses. PMID:25287260

  10. Flaviviruses, an expanding threat in public health: focus on dengue, West Nile, and Japanese encephalitis virus.

    PubMed

    Daep, Carlo Amorin; Muñoz-Jordán, Jorge L; Eugenin, Eliseo Alberto

    2014-12-01

    The flaviviruses dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors (Aedes and Culex spp.), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses.

  11. West Nile virus in horses during the summer and autumn seasons of 2015 and 2016, Portugal.

    PubMed

    Barros, Sílvia C; Ramos, Fernanda; Fagulha, Teresa; Duarte, Margarida; Henriques, Ana Margarida; Waap, Helga; Luís, Tiago; Costa, Teresa; Amador, Rita; Quintans, Sofia; Fevereiro, Miguel

    2017-12-01

    West Nile fever (WNF) is an emergent disease in Europe, under surveillance in the European Union. Following a 5-year period of apparent silence (autumn 2010 to summer 2015), West Nile virus (WNV) reemerged in the South of Portugal, in July 2015. Here we present data from the onset, geographic location within mainland Portugal, and outcome of clinical cases of WNV infection in horses in 2015 and 2016. During the transmission seasons of 2015 and 2016, twenty-seven horses, most symptomatic (n=20) were found positive to IgM, pr-E immunoglobulins and VNT, leading to the subsequent report to Animal Disease Notification System of the European Commission (ADNS) by the Portuguese National Authority for Animal Health. Outbreaks occurred in the middle summer (August) and early/mid autumn (October/November) of 2015 and 2016, in the southern regions of the country (Alentejo and Algarve). Compared with the previous WNV transmission seasons of 2004 and 2010, a higher number of cases were reported in 2015 and 2016. The results of our study contribute to increase information concerning the geographic areas affected and time period for WNV transmission risk in Portugal. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. A review of West Nile and Usutu virus co-circulation in Europe: how much do transmission cycles overlap?

    PubMed

    Nikolay, Birgit

    2015-10-01

    Due to the increasing global spread of arboviruses, the geographic extent of virus co-circulation is expanding. This complicates the diagnosis of febrile conditions and can have direct effects on the epidemiology. As previously demonstrated, subsequent infections by two closely related viruses, such as those belonging to the Japanese encephalitis virus (JEV) serocomplex, can lead to partial or complete cross-immunity, altering the risk of infections or the outcome of disease. Two flaviviruses that may interact at population level are West Nile virus (WNV) and Usutu virus (USUV). These pathogens have antigenic cross-reactivity and affect human and animal populations throughout Europe. This systematic review investigates the overlap of WNV and USUV transmission cycles, not only geographically but also in terms of host and vector ranges. Co-circulation of WNV and USUV was reported in 10 countries and the viruses were found to infect 34 common bird species belonging to 11 orders. Moreover, four mosquito species are potential vectors for both viruses. Taken together, these data suggest that WNV and USUV transmission overlaps substantially in Europe and highlight the importance of further studies investigating the interactions between the two viruses within host and vector populations. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. West Nile Virus in Mosquitoes of Iranian Wetlands.

    PubMed

    Bagheri, Masoomeh; Terenius, Olle; Oshaghi, Mohammad Ali; Motazakker, Morteza; Asgari, Sassan; Dabiri, Farrokh; Vatandoost, Hassan; Mohammadi Bavani, Mulood; Chavshin, Ali Reza

    2015-12-01

    The West Nile virus (WNV) transmission cycle includes a wide range of migratory wetland birds as reservoirs, mosquitoes as biological vectors, and equines and humans as dead-end hosts. Despite the presence of potential vector species, there is no information about the existence of WNV in mosquito vectors in Iran. The Iranian West Azerbaijan Province is located in the northwestern part of Iran and has borders with Turkey, Iraq, Armenia, and the Republic of Azerbaijan. The current study was conducted to identify the wetland mosquitoes of the West Azerbaijan Province and their infection with WNV. In this study, 2143 specimens were collected, comprising 1541 adults and 602 larvae. Six species belonging to four genera were collected and identified: Anopheles maculipennis sensu lato (s.l.), Culex (Cx.) hortensis, Cx. pipiens s.l., Cx. theileri, Culiseta longiareolata, and Aedes (Ae.) (Ochlerotatus) caspius. In total, 45 pools of mosquitoes were examined. Two of the adult pools collected from the same location showed the presence of WNV in Ae. (Och.) caspius, from Sangar, Makoo County, as confirmed by PCR and sequencing. Due to the discovery of WNV in the mosquito population of the region, and the presence of wetlands and significant populations of migratory birds, the health sector should carefully monitor the factors involved in the cycle of this disease.

  14. Structural gene (prME) chimeras of St Louis encephalitis virus and West Nile virus exhibit altered in vitro cytopathic and growth phenotypes

    PubMed Central

    Maharaj, Payal D.; Anishchenko, Michael; Langevin, Stanley A.; Fang, Ying; Reisen, William K.

    2012-01-01

    Despite utilizing the same avian hosts and mosquito vectors, St Louis encephalitis virus (SLEV) and West Nile virus (WNV) display dissimilar vector-infectivity and vertebrate-pathogenic phenotypes. SLEV exhibits a low oral infection threshold for Culex mosquito vectors and is avirulent in avian hosts, producing low-magnitude viraemias. In contrast, WNV is less orally infective to mosquitoes and elicits high-magnitude viraemias in a wide range of avian species. In order to identify the genetic determinants of these different phenotypes and to assess the utility of mosquito and vertebrate cell lines for recapitulating in vivo differences observed between these viruses, reciprocal WNV and SLEV pre-membrane and envelope protein (prME) chimeric viruses were generated and growth of these mutant viruses was characterized in mammalian (Vero), avian (duck) and mosquito [Aedes (C6/36) and Culex (CT)] cells. In both vertebrate lines, WNV grew to 100-fold higher titres than SLEV, and growth and cytopathogenicity phenotypes, determined by chimeric phenotypes, were modulated by genetic elements outside the prME gene region. Both chimeras exhibited distinctive growth patterns from those of SLEV in C6/36 cells, indicating the role of both structural and non-structural gene regions for growth in this cell line. In contrast, growth of chimeric viruses was indistinguishable from that of virus containing homologous prME genes in CT cells, indicating that structural genetic elements could specifically dictate growth differences of these viruses in relevant vectors. These data provide genetic insight into divergent enzootic maintenance strategies that could also be useful for the assessment of emergence mechanisms of closely related flaviviruses. PMID:21940408

  15. MOLECULAR EVOLUTION OF WEST NILE VIRUS IN A NORTHERN TEMPERATE REGION: CONNECTICUT, USA 1999–2008

    PubMed Central

    Armstrong, Philip M.; Vossbrinck, Charles R.; Andreadis, Theodore G.; Anderson, John F.; Pesko, Kendra N.; Newman, Ruchi M.; Lennon, Niall J.; Birren, Bruce W.; Ebel, Gregory D.; Henn, Mathew R.

    2011-01-01

    West Nile virus (WNV) has become firmly established in northeastern U.S., reemerging every summer since its introduction into North America in 1999. To determine whether WNV overwinters locally or is reseeded annually, we examined the patterns of viral lineage persistence and replacement in Connecticut over 10 consecutive transmission seasons by phylogenetic analysis. In addition, we compared the full protein coding sequence among WNV isolates to search for evidence of convergent and adaptive evolution. Viruses sampled from Connecticut segregated into a number of well-supported subclades by year of isolation with few clades persisting ≥2 years. Similar viral strains were dispersed in different locations across the state and divergent strains appeared within a single location during a single transmission season, implying widespread movement and rapid colonization of virus. Numerous amino acid substitutions arose in the population but only one change, V→A at position 159 of the envelope protein, became permanently fixed. Several instances of parallel evolution were identified in independent lineages, including one amino acid change in the NS4A protein that appears to bepositively selected. Our results suggest that annual reemergence of WNV is driven by both reintroduction and local-overwintering of virus. Despite ongoing evolution of WNV, most amino acid variants occurred at low frequencies and were transient in the virus population. PMID:21723580

  16. West nile virus infections suppress early viral RNA synthesis and avoid inducing the cell stress granule response.

    PubMed

    Courtney, S C; Scherbik, S V; Stockman, B M; Brinton, M A

    2012-04-01

    West Nile virus (WNV) recently became endemic in the United States and is a significant cause of human morbidity and mortality. Natural WNV strain infections do not induce stress granules (SGs), while W956IC (a lineage 2/1 chimeric WNV infectious clone) virus infections produce high levels of early viral RNA and efficiently induce SGs through protein kinase R (PKR) activation. Additional WNV chimeric viruses made by replacing one or more W956IC genes with the lineage 1 Eg101 equivalent in the W956IC backbone were analyzed. The Eg-NS4b+5, Eg-NS1+3+4a, and Eg-NS1+4b+5 chimeras produced low levels of viral RNA at early times of infection and inefficiently induced SGs, suggesting the possibility that interactions between viral nonstructural proteins and/or between viral nonstructural proteins and cell proteins are involved in suppressing early viral RNA synthesis and membrane remodeling during natural WNV strain infections. Detection of exposed viral double-stranded RNA (dsRNA) in W956IC-infected cells suggested that the enhanced early viral RNA synthesis surpassed the available virus-induced membrane protection and allowed viral dsRNA to activate PKR.

  17. West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection.

    PubMed

    Davis, Carl W; Nguyen, Hai-Yen; Hanna, Sheri L; Sánchez, Melissa D; Doms, Robert W; Pierson, Theodore C

    2006-02-01

    The C-type lectins DC-SIGN and DC-SIGNR bind mannose-rich glycans with high affinity. In vitro, cells expressing these attachment factors efficiently capture, and are infected by, a diverse array of appropriately glycosylated pathogens, including dengue virus. In this study, we investigated whether these lectins could enhance cellular infection by West Nile virus (WNV), a mosquito-borne flavivirus related to dengue virus. We discovered that DC-SIGNR promoted WNV infection much more efficiently than did DC-SIGN, particularly when the virus was grown in human cell types. The presence of a single N-linked glycosylation site on either the prM or E glycoprotein of WNV was sufficient to allow DC-SIGNR-mediated infection, demonstrating that uncleaved prM protein present on a flavivirus virion can influence viral tropism under certain circumstances. Preferential utilization of DC-SIGNR was a specific property conferred by the WNV envelope glycoproteins. Chimeras between DC-SIGN and DC-SIGNR demonstrated that the ability of DC-SIGNR to promote WNV infection maps to its carbohydrate recognition domain. WNV virions and subviral particles bound to DC-SIGNR with much greater affinity than DC-SIGN. We believe this is the first report of a pathogen interacting more efficiently with DC-SIGNR than with DC-SIGN. Our results should lead to the discovery of new mechanisms by which these well-studied lectins discriminate among ligands.

  18. Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I.

    PubMed

    Wang, Penghua; Arjona, Alvaro; Zhang, Yue; Sultana, Hameeda; Dai, Jianfeng; Yang, Long; LeBlanc, Philippe M; Doiron, Karine; Saleh, Maya; Fikrig, Erol

    2010-10-01

    Caspase-12 has been shown to negatively modulate inflammasome signaling during bacterial infection. Its function in viral immunity, however, has not been characterized. We now report an important role for caspase-12 in controlling viral infection via the pattern-recognition receptor RIG-I. After challenge with West Nile virus (WNV), caspase-12-deficient mice had greater mortality, higher viral burden and defective type I interferon response compared with those of challenged wild-type mice. In vitro studies of primary neurons and mouse embryonic fibroblasts showed that caspase-12 positively modulated the production of type I interferon by regulating E3 ubiquitin ligase TRIM25-mediated ubiquitination of RIG-I, a critical signaling event for the type I interferon response to WNV and other important viral pathogens.

  19. Sentinel Chicken Seroconversions Track Tangential Transmission of West Nile Virus to Humans in the Greater Los Angeles Area of California

    PubMed Central

    Kwan, Jennifer L.; Kluh, Susanne; Madon, Minoo B.; Nguyen, Danh V.; Barker, Christopher M.; Reisen, William K.

    2010-01-01

    In Los Angeles, California, West Nile virus (WNV) has followed a pattern of emergence, amplification, subsidence, and resurgence. A time series cross-correlation analysis of human case counts and sentinel chicken seroconversions revealed temporal concordance indicating that chicken seroconversions tracked tangential transmission of WNV from the basic passeriform-Culex amplification cycle to humans rather than antecedent enzootic amplification. Sentinel seroconversions provided the location and time of transmission as opposed to human cases, which frequently were reported late and were assumed to be acquired 2–14 days before disease onset at their residence. Cox models revealed that warming degree-days were associated with the increased risk of seroconversion, whereas elevated herd immunity in peridomestic birds dampened seroconversion risk. Spatially, surveillance data collected within a 5 km radius of flock locations 15–28 days before the bleed date were most predictive of a seroconversion. In urban Los Angeles, sentinel chicken seroconversions could be used as an outcome measure in decision support for emergency intervention. PMID:21036853

  20. Application of a degree-day model of West Nile virus transmission risk to the East Coast of the United States of America.

    PubMed

    Konrad, Sarah K; Miller, Scott N

    2012-11-01

    A geographical information systems model that identifies regions of the United States of America (USA) susceptible to West Nile virus (WNV) transmission risk is presented. This system has previously been calibrated and tested in the western USA; in this paper we use datasets of WNV-killed birds from South Carolina and Connecticut to test the model in the eastern USA. Because their response to WNV infection is highly predictable, American crows were chosen as the primary source for model calibration and testing. Where crow data are absent, other birds are shown to be an effective substitute. Model results show that the same calibrated model demonstrated to work in the western USA has the same predictive ability in the eastern USA, allowing for a continental-scale evaluation of the transmission risk of WNV at a daily time step. The calibrated model is independent of mosquito species and requires inputs of only local maximum and minimum temperatures. Of benefit to the general public and vector control districts, the model predicts the onset of seasonal transmission risk, although it is less effective at identifying the end of the transmission risk season.

  1. Ophthalmologic and oculopathologic findings in red-tailed hawks and Cooper's hawks with naturally acquired West Nile virus infection.

    PubMed

    Pauli, Amy M; Cruz-Martinez, Luis A; Ponder, Julia B; Redig, Patrick T; Glaser, Amy L; Klauss, Gia; Schoster, James V; Wünschmann, Arno

    2007-10-15

    To assess ophthalmologic features and ocular lesions in red-tailed hawks and Cooper's hawks naturally infected with West Nile virus (WNV). Original study. 13 hawks. All hawks underwent complete ophthalmic examinations including slit lamp biomicroscopy and binocular indirect ophthalmoscopy. Eleven hawks were euthanized because of a grave prognosis; complete necropsies were performed. Eyes, brain, heart, and kidneys were processed for histologic and immunohistochemical examinations. Pooled tissue homogenates and aqueous humor samples were assessed for WNV nucleic acid via PCR assay, and anti-WNV antibody titers in aqueous humor and plasma were determined. All birds had similar funduscopic abnormalities including exudative chorioretinal lesions and chorioretinal scarring in a geographic or linear pattern. Eleven birds were euthanized, and 2 birds were released. Plasma from both released hawks and plasma and aqueous humor of all euthanized hawks that were evaluated contained anti-WNV antibodies. Except for 1 hawk, all euthanized hawks had WNV-associated disease (determined via detection of WNV antigen or nucleic acid in at least 1 organ). Histopathologic ocular abnormalities, most commonly pectenitis, were detected in all euthanized birds; several birds had segmental choroiditis, often with corresponding segmental retinal atrophy. West Nile virus antigen was detected in the retinas of 9 of the euthanized birds. In 2 hawks, WNV antigen was detected in the retina only. Results indicated that funduscopically detectable chorioretinal lesions appear to be associated with WNV disease in hawks. Detection of ocular lesions may aid in antemortem or postmortem diagnosis of this condition.

  2. Estimating the economic impact of a possible equine and human epidemic of West Nile virus infection in Belgium

    PubMed Central

    Humblet, Marie-France; Vandeputte, Sébastien; Fecher-Bourgeois, Fabienne; Léonard, Philippe; Gosset, Christiane; Balenghien, Thomas; Durand, Benoît; Saegerman, Claude

    2016-01-01

    This study aimed at estimating, in a prospective scenario, the potential economic impact of a possible epidemic of WNV infection in Belgium, based on 2012 values for the equine and human health sectors, in order to increase preparedness and help decision-makers. Modelling of risk areas, based on the habitat suitable for Culex pipiens, the main vector of the virus, allowed us to determine equine and human populations at risk. Characteristics of the different clinical forms of the disease based on past epidemics in Europe allowed morbidity among horses and humans to be estimated. The main costs for the equine sector were vaccination and replacement value of dead or euthanised horses. The choice of the vaccination strategy would have important consequences in terms of cost. Vaccination of the country’s whole population of horses, based on a worst-case scenario, would cost more than EUR 30 million; for areas at risk, the cost would be around EUR 16–17 million. Regarding the impact on human health, short-term costs and socio-economic losses were estimated for patients who developed the neuroinvasive form of the disease, as no vaccine is available yet for humans. Hospital charges of around EUR 3,600 for a case of West Nile neuroinvasive disease and EUR 4,500 for a case of acute flaccid paralysis would be the major financial consequence of an epidemic of West Nile virus infection in humans in Belgium. PMID:27526394

  3. Estimating the economic impact of a possible equine and human epidemic of West Nile virus infection in Belgium.

    PubMed

    Humblet, Marie-France; Vandeputte, Sébastien; Fecher-Bourgeois, Fabienne; Léonard, Philippe; Gosset, Christiane; Balenghien, Thomas; Durand, Benoît; Saegerman, Claude

    2016-08-04

    This study aimed at estimating, in a prospective scenario, the potential economic impact of a possible epidemic of WNV infection in Belgium, based on 2012 values for the equine and human health sectors, in order to increase preparedness and help decision-makers. Modelling of risk areas, based on the habitat suitable for Culex pipiens, the main vector of the virus, allowed us to determine equine and human populations at risk. Characteristics of the different clinical forms of the disease based on past epidemics in Europe allowed morbidity among horses and humans to be estimated. The main costs for the equine sector were vaccination and replacement value of dead or euthanised horses. The choice of the vaccination strategy would have important consequences in terms of cost. Vaccination of the country's whole population of horses, based on a worst-case scenario, would cost more than EUR 30 million; for areas at risk, the cost would be around EUR 16-17 million. Regarding the impact on human health, short-term costs and socio-economic losses were estimated for patients who developed the neuroinvasive form of the disease, as no vaccine is available yet for humans. Hospital charges of around EUR 3,600 for a case of West Nile neuroinvasive disease and EUR 4,500 for a case of acute flaccid paralysis would be the major financial consequence of an epidemic of West Nile virus infection in humans in Belgium. This article is copyright of The Authors, 2016.

  4. Evidence of enzootic circulation of West Nile virus (Nea Santa-Greece-2010, lineage 2), Greece, May to July 2011.

    PubMed

    Chaskopoulou, A; Dovas, Ci; Chaintoutis, Sc; Bouzalas, I; Ara, G; Papanastassopoulou, M

    2011-08-04

    A West Nile virus (WNV) surveillance network including sentinel chickens was deployed in Thessaloniki county, Greece, from May to July 2011. For the first time in summer 2011, a chicken WNV isolate from 6 July was molecularly identified. The partial NS3 sequence was identical to that of the Nea Santa-Greece-2010 WNV lineage 2, detected in central Macedonia in 2010. This suggests that WNV is actively circulating in central Macedonia and that it may have overwintered in northern Greece.

  5. The mosquito borne West Nile virus infection: is it threating to Egypt or a neglected endemic disease?

    PubMed

    El-Bahnasawy, Mamdouh M; Khater, Mai Khater M; Morsy, Tosson A

    2013-04-01

    West Nile virus (WNV) is a mosquito-borne zoonotic arbovirus belonging to the genus Flavivirus in the family Flaviviridae. The virus is found in temperate and tropical regions worldwide, but first identified in the West Nile sub-region in the East African nation of Uganda in 1937. Prior to the mid-1990s WNV infection was sporadically and considered a minor risk for humans, until an outbreak in Algeria in 1994, with cases of WNV-caused encephalitis, and the first large outbreak in Romania in 1996; with a high number of cases with neuroinvasive disease. WNV has now spread globally to Europe beyond the Mediterranean Basin and the United States, is now considered to be an endemic pathogen in worldwide especially in Africa The WNV transmission is mainly b y v a rious mosquitoes species, also tickswere incriminated The birds especially passerines are the most commonly infected animal and serving as the prime reservoir host In Egypt more than 110 mosquito species and subspecies and more than 32 genera of ticks were identified. Besides, not less than 150 species of migratory birds visit Egypt annually in addition to 350 resident ones. This review provided an overview of the current understanding flaviviruses mainly WNFV. Primary care physician and senior nurse should be able to include the disaster diseases in differential diagnosis of various clinical conditions. They should take a thorough history to request specific dependable laboratory test(s) as soon as possible, and positive patient should be transferred to the fever hospital.

  6. Ecological niche modelling of potential West Nile virus vector mosquito species and their geographical association with equine epizootics in Italy.

    PubMed

    Mughini-Gras, Lapo; Mulatti, Paolo; Severini, Francesco; Boccolini, Daniela; Romi, Roberto; Bongiorno, Gioia; Khoury, Cristina; Bianchi, Riccardo; Montarsi, Fabrizio; Patregnani, Tommaso; Bonfanti, Lebana; Rezza, Giovanni; Capelli, Gioia; Busani, Luca

    2014-01-01

    In Italy, West Nile virus (WNV) equine outbreaks have occurred annually since 2008. Characterizing WNV vector habitat requirements allows for the identification of areas at risk of viral amplification and transmission. Maxent-based ecological niche models were developed using literature records of 13 potential WNV Italian vector mosquito species to predict their habitat suitability range and to investigate possible geographical associations with WNV equine outbreak occurrence in Italy from 2008 to 2010. The contribution of different environmental variables to the niche models was also assessed. Suitable habitats for Culex pipiens, Aedes albopictus, and Anopheles maculipennis were widely distributed; Culex modestus, Ochlerotatus geniculatus, Ochlerotatus caspius, Coquillettidia richiardii, Aedes vexans, and Anopheles plumbeus were concentrated in north-central Italy; Aedes cinereus, Culex theileri, Ochlerotatus dorsalis, and Culiseta longiareolata were restricted to coastal/southern areas. Elevation, temperature, and precipitation variables showed the highest predictive power. Host population and landscape variables provided minor contributions. WNV equine outbreaks had a significantly higher probability to occur in habitats suitable for Cx. modestus and Cx. pipiens, providing circumstantial evidence that the potential distribution of these two species coincides geographically with the observed distribution of the disease in equines.

  7. West Nile Virus: Seroprevalence in Animals in Palestine and Israel.

    PubMed

    Azmi, Kifaya; Tirosh-Levy, Sharon; Manasrah, Mu'taz; Mizrahi, Rotem; Nasereddin, Abed; Al-Jawabreh, Amer; Ereqat, Suheir; Abdeen, Ziad; Lustig, Yaniv; Gelman, Boris; Schvartz, Gili; Steinman, Amir

    2017-08-01

    West Nile virus (WNV) epidemiological situation in Israel and Palestine, due to their unique location, draws attention following to the global spread of West Nile fever (WNF). Although much information is available from Israel on clinical cases and prevalence of WNV, clinical cases are rarely reported in Palestine, and prevalence is not known. The objectives of this study were to determine WNV seroprevalence in various domestic animals in Palestine and to reevaluate current seroprevalence, force of infection, and risk factors for WNV exposure in horses in Israel. Sera samples were collected from 717 animals from Palestine and Israel (460 horses, 124 donkeys, 3 mules, 50 goats, 45 sheep, and 35 camels). Two hundred and ten horses were sampled twice. The level of WNV antibodies was determined using commercial Enzyme-linked Immunosorbent Assay (ELISA) Kit. Seroprevalence in equids was 73%. Seroprevalence in Israel (84.6%) was significantly higher than in Palestine (48.6%). Seroprevalence in horses (82.6%) was significantly higher than in donkeys and mules (39.3%). Multivariable statistical analysis showed that geographical area, landscape features (altitude), environmental factors (land surface temperature during the day [LSTD]), species, and age significantly influenced WNV seroprevalence. Fourteen of 95 (14.7%) sheep and goats and 14/35 camels (40%) sampled in Palestine were seropositive for WNV. Of the horses that were sampled twice, 82.8% were seropositive for WNV at the first sampling, and all remained seropositive. Three of the seronegative horses, all from Palestine, converted to positive when resampled (8.5%). The results indicate that domestic animals in Palestine were infected with WNV in the past, and the seroconversion indicates that WNV was circulating in Palestine in the summer of 2014. Control measures to prevent human infection should be implemented in Palestine. Anti WNV antibodies in domestic animals suggest that those species can be used as

  8. West Nile Disease Epidemiology in North-West Africa: Bibliographical Review.

    PubMed

    Benjelloun, A; El Harrak, M; Belkadi, B

    2016-12-01

    West Nile fever (WNF) or West Nile disease (WND) is a mosquito-borne viral disease that can affect birds, humans and horses. West Nile virus (WNV) is a member of the genus Flavivirus in the family Flaviviridae. WNV is maintained in a mosquito-bird-mosquito transmission cycle, whereas humans and horses are considered dead-end hosts. In human and horses, symptoms range from unapparent infection to mild febrile illness, meningitis, encephalitis or death. WNV has a wide geographical range that includes portions of Europe, Asia, Africa, Australia (Kunjin virus), and in North, Central and South America. Migratory birds are thought to be primarily responsible for virus dispersal, including reintroduction of WNV from endemic areas into regions that experience sporadic outbreaks (Fields Virology, 2001, Lippincott Williams and Wilkins, Philadelphia, Pennsylvania, USA, 1043-1125). The occurrence of disease in humans and animals along with birds and mosquitoes surveillance for WNV activity demonstrates that the virus range has dramatically expanded including North, Central and South America as well as Europe and countries facing the Mediterranean Basin. WND infection in humans has been reported in Morocco in 1996 (Virologie, 1, 1997, 248), in Tunisia in 2007 (Ann. N. Y. Acad., 951, 2001, 117) (Med. Trop., 61, 2001, 487) and 2003 (Epidémiologie de la fièvre West Nile, 2012, Thèse de doctorat, Université Montpellier II, Sciences et techniques du Langueduc, Montpellier, France), and in Algeria in 1994 (Rev. Sci. Tech., 31, 2012, 829). Outbreaks of equine encephalitis have been also reported in Morocco in 1996 (Bull. OIE, 11, 1996, 867), in 2003 (Emerg. Infect. Dis., 11, 2005, 306) and in 2010 (World Animal Health Information Database. WAHID, 2010). Serological evidence of WNV has been demonstrated in the three countries in many species. The aim of this review was to assess the epidemiological situation of WND in north-west Africa comprising Morocco, Algeria and Tunisia, with

  9. A Risk Factor Analysis of West Nile Virus: Extraction of Relationships from a Neural-Network Model

    NASA Astrophysics Data System (ADS)

    Ghosh, Debarchana; Guha, Rajarshi

    The West Nile Virus (WNV) is an infectious disease spreading rapidly throughout the United States, causing illness among thousands of birds, animals, and humans. The broad categories of risk factors underlying WNV incidences are: environmental, socioeconomic, built-environment, and existing mosquito abatement policies. Computational neural network (CNN) model was developed to understand the occurrence of WNV infected dead birds because of their ability to capture complex relationships with higher accuracy than linear models. In this paper, we describe a method to interpret a CNN model by considering the final optimized weights. The research was conducted in the Metropolitan area of Minnesota, which had experienced significant outbreaks from 2002 till present.

  10. Persistent West Nile Virus Transmission and the Apparent Displacement St. Louis Encephalitis Virus in Southeastern California, 2003−2006

    PubMed Central

    REISEN, WILLIAM K.; LOTHROP, HUGH D.; WHEELER, SARAH S.; KENNSINGTON, MARC; GUTIERREZ, ARTURO; FANG, YING; GARCIA, SANDRA; LOTHROP, BRANKA

    2008-01-01

    West Nile virus (family Flaviviridae, genus Flavivirus, WNV) invaded the Colorado Desert biome of southern California during summer 2003 and seemed to displace previously endemic St. Louis encephalitis virus (family Flaviviridae, genus Flavivirus, SLEV, an antigenically similar Flavivirus in the Japanese encephalitis virus serocomplex). Western equine encephalomyelitis virus (family Togaviridae, genus Alphavirus, WEEV), an antigenically distinct Alphavirus, was detected during 2005 and 2006, indicating that conditions were suitable for encephalitis virus introduction and detection. Cross-protective “avian herd immunity” due to WNV infection possibly may have prevented SLEV reintroduction and/or amplification to detectable levels. During 2003−2006, WNV was consistently active at wetlands and agricultural habitats surrounding the Salton Sea where Culex tarsalis Coquillett served as the primary enzootic maintenance and amplification vector. Based on published laboratory infection studies and the current seroprevalence estimates, house sparrows, house finches, and several Ardeidae may have been important avian amplifying hosts in this region. Transmission efficiency may have been dampened by high infection rates in incompetent avian hosts, including Gamble's quail, mourning doves, common ground doves, and domestic pigeons. Early season WNV amplification and dispersal from North Shore in the southeastern portion of the Coachella Valley resulted in sporadic WNV incursions into the urbanized Upper Valley near Palm Springs, where Culex pipiens quinquefasciatus Say was the primary enzootic and bridge vector. Although relatively few human cases were detected during the 2003−2006 period, all were concentrated in the Upper Valley and were associated with high human population density and WNV infection in peridomestic populations of Cx. p. quinquefasciatus. Intensive early mosquito control during 2006 seemed to interrupt and delay transmission, perhaps setting the stage

  11. Mosquito politics: local vector control policies and the spread of West Nile Virus in the Chicago region.

    PubMed

    Tedesco, Carmen; Ruiz, Marilyn; McLafferty, Sara

    2010-11-01

    Differences in mosquito control practices at the local level involve the interplay of place, scale and politics. During the Chicago West Nile Virus (WNV) outbreak of 2002, mosquito abatement districts represent distinct suburban clusters of human WNV cases, independent of characteristics of the local population, housing and physical environment. We examine how the contrasting actions of four districts reveal a distinct local politics of mosquito control that may have contributed to local-scale geographic differences in WNV incidence. This politics is rooted in political, economic and philosophical differences within and between administrative boundaries. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Evidence for a vast peptide overlap between West Nile virus and human proteomes.

    PubMed

    Capone, Giovanni; Pagoni, Maria; Delfino, Antonella Pesce; Kanduc, Darja

    2013-10-01

    The primary amino acid sequence of West Nile virus (WNV) polyprotein, GenBank accession number M12294, was analyzed by computional biology. WNV is a mosquito-borne neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans. Using pentapeptides as scanning units and the perfect peptide match program from PIR International Protein Sequence Database, we compared the WNV polyprotein and the human proteome. WNV polyprotein showed significant sequence similarities to a number of human proteins. Several of these proteins are involved in embryogenesis, neurite outgrowth, cortical neuron branching, formation of mature synapses, semaphorin interactions, and voltage dependent L-type calcium channel subunits. The biocomputional study suggest that common amino acid segments might represent a potential platform for further studies on the neurological pathophysiology of WNV infections. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Demographic and Clinical Factors Associated with Persistent Symptoms after West Nile Virus Infection

    PubMed Central

    Cook, Robert L.; Xu, Xiaohui; Yablonsky, Eric J.; Sakata, Nikole; Tripp, Jennifer H.; Hess, Rachel; Piazza, Paolo; Rinaldo, Charles R.

    2010-01-01

    Prognosis varies among persons with West Nile virus (WNV) infection, but the most important factors associated with persistent symptoms are not clear. In this cross-sectional study, 265 persons with symptomatic WNV infection during 2006–2008 completed a survey a mean of 7.7 months after diagnosis. We determined the association of demographic and clinical characteristics to the most common symptoms. Of 214 persons infected ≥ 6 months, 53% reported one or more persistent symptoms, including fatigue, muscle aches, decreased activity, difficulty with memory, and difficulty concentrating. Persons with neuroinvasive disease, hypertension, or diabetes were significantly more likely to report persistent symptoms, whereas age, sex, and time since infection were not associated with persistent symptoms. In conclusion, persistent symptoms persisted in most persons for more than six months after symptomatic WNV infection. Improved strategies for prevention and treatment are needed. PMID:21036852

  14. West Nile virus transmission via organ transplantation and blood transfusion - Louisiana, 2008.

    PubMed

    2009-11-20

    Three years after the introduction and spread of West Nile virus (WNV) in the United States, transmission through blood transfusion and solid organ transplantation was documented in 2002. Within a year, these findings led to nationwide screening of blood donors for WNV. Although screening is extremely sensitive, current methods still do not detect all WNV-infected blood donations, and organ donors are not screened routinely. In October 2008, the Louisiana Department of Health (LDH) was notified of a heart transplant recipient with suspected West Nile neuroinvasive disease (WNND). LDH launched an investigation to confirm the diagnosis and determine whether the organ recipient's infection was derived from the organ donor or blood products the donor received before organ donation. The investigation concluded that two cases of probable transfusion-transmitted WNV resulted from a common blood donor; one infection resulted in WNND via an organ donor, and the other resulted in asymptomatic WNV infection via blood transfusion directly. This investigation also found that criteria used by the blood-screening laboratory to screen the implicated blood donation for WNV were less stringent than criteria used by other blood collection centers in the area. Use of the more stringent screening criteria might have detected the WNV and prevented the blood donation from being used. To increase the likelihood of detecting WNV-positive donations, blood centers should use the most sensitive screening criteria feasible and communicate frequently with nearby blood centers on screening results during times of high WNV activity in their geographic area. In addition, health-care providers should consider WNND as a possible cause of neurologic complications in patients after blood transfusion or organ transplantation.

  15. Long term impacts of combined sewer overflow remediation on water quality and population dynamics of Culex quinquefasciatus, the main urban West Nile virus vector in Atlanta, GA.

    PubMed

    Lund, Andrea; McMillan, Joseph; Kelly, Rosmarie; Jabbarzadeh, Shirin; Mead, Daniel G; Burkot, Thomas R; Kitron, Uriel; Vazquez-Prokopec, Gonzalo M

    2014-02-01

    Combined sewers are a significant source of urban water pollution due to periodic discharges into natural streams. Such events (called combined sewer overflows, or CSOs) contribute to the impairment of natural waterways and are associated with increased mosquito productivity and elevated risk of West Nile virus transmission. We investigated the impact of CSOs on water quality and immature mosquito productivity in the city of Atlanta, Georgia, one year before and four years after CSO facility remediation. Water quality (ammonia, phosphate, nitrate and dissolved oxygen concentrations), immature mosquitoes (larvae and pupae), water temperature and rainfall were quantified biweekly between June-October at two urban creeks during 2008-2012. A before-after control-intervention design tested the impact of remediation on mosquito productivity and water quality, whereas generalized linear mixed-effect models quantified the factors explaining the long term impacts of remediation on mosquito productivity. Ammonia and phosphate concentrations and late immature (fourth-instar and pupae) mosquito populations were significantly higher in CSO than in non-CSO creeks, while dissolved oxygen concentrations were lower. Remediation significantly improved water quality estimates (particularly ammonia and dissolved oxygen) and reduced the number of overflows, mosquito productivity and the overall contribution of CSO-affected streams as sources of vectors of West Nile virus. The quality of water in CSOs provided a suitable habitat for immature mosquitoes. Remediation of the CSO facility through the construction of a deep storage tunnel improved water quality indices and reduced the productivity of mosquito species that can serve as vectors of West Nile virus. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Current developments in understanding of West Nile virus central nervous system disease.

    PubMed

    Tyler, Kenneth L

    2014-06-01

    West Nile virus (WNV) is the most important cause of epidemic encephalitis in the United States. We review articles published in the last 18 months related to the epidemiology, immunology, clinical features, and treatment of this disease. There was a resurgence in WNV disease in the United States in 2012. The WNV strain now predominant in the United States (NA/WN02) differs from the initial emergent isolate in 1999 (NY99). However, differences in the genetics of currently circulating United States WNV strains do not explain variations in epidemic magnitude or disease severity. Innate and acquired immunity are critical in control of WNV, and in some cases pathways are central nervous system specific. The clinical features of infection are now well understood, although nonconfirmed observations of chronic viral excretion in urine remain controversial. There is no specific antiviral therapy for WNV, but studies of antivirals specific for other flaviviruses may identify agents with promise against WNV. Phase I and II human WNV vaccine clinical trials have established that well tolerated and immunogenic WNV vaccines can be developed. WNV remains an important public health problem. Although recent studies have significantly increased our understanding of host immune and genetic factors involved in control of WNV infection, no specific therapy is yet available. Development of a well tolerated, immunogenic, and effective vaccine against WNV is almost certainly feasible, but economic factors and the lack of predictability of the magnitude and location of outbreaks are problematic for designing phase III trials and ultimate licensure.

  17. Factors associated with the risk of West Nile Virus among crows in New York State

    PubMed Central

    DeCarlo, C. H.; Clark, A. B.; McGowan, K. J.; Ziegler, P. E.; Glaser, A. L.; Szonyi, B.; Mohammed, H. O.

    2010-01-01

    West Nile virus (WNV) is transmitted between avian hosts in enzootic cycles by a mosquito vector. The virus has significant disease effects on humans and equines when it bridges into an epizootic cycle. Since the initial epidemic of WNV in 1999, perennial outbreaks in New York State suggest the local establishment of natural foci with perpetuation of the virus among susceptible hosts rather than reintroduction of the virus. The factors that play a role in the perpetuation of the virus are not fully understood. American crows (Corvus brachyrhynchos) are known to be highly susceptible to infection with the virus. We investigate the factors that put crows at risk of infection in Tompkins County, New York during the period of 2000 through 2008 in a case-control study. Cases were crow carcasses that were found dead and tested positive for WNV using real time reverse transcription (RT-PCR) or VecTestR. Data on putative risk factors were collected and assessed for significance of association with the presence of WNV using logistic regression analysis to evaluate the significance of each factor while simultaneously controlling for the effect of others. The risk of a crow carcass testing WNV positive varied with age, season of the year, and ecological area where the carcass was found. Crows that were more than one year old were 4 times more likely to be WNV positive in comparison to birds that were less than one year of age. It was three times more likely to find WNV positive carcasses in residential areas in comparison to rural areas. The risk of testing WNV positive did not vary by sex of the crow carcasses. PMID:20707862

  18. Genetic Determinants of Differential Oral Infection Phenotypes of West Nile and St. Louis Encephalitis Viruses in Culex spp. Mosquitoes

    PubMed Central

    Maharaj, Payal D.; Bolling, Bethany G.; Anishchenko, Michael; Reisen, William K.; Brault, Aaron C.

    2014-01-01

    St. Louis encephalitis virus (SLEV) has shown greater susceptibility to oral infectivity than West Nile virus (WNV) in Culex mosquitoes. To identify the viral genetic elements that modulate these disparate phenotypes, structural chimeras (WNV–pre-membrane [prM] and envelope [E] proteins [prME]/SLEV.IC (infectious clone) and SLEV-prME/WNV.IC) were constructed in which two of the structural proteins, the prM and E, were interchanged between viruses. Oral dose–response assessment with the chimeric/parental WNV and SLEV was performed to characterize the infection phenotypes in Culex mosquitoes by artificial blood meals. The median infectious dose required to infect 50% of Cx. quinquefasciatus with WNV was indistinguishable from that of the SLEV-prME/WNV.IC chimeric virus. Similarly, SLEV and WNV-prME/SLEV.IC virus exhibited an indistinguishable oral dose–response relationship in Cx. quinquefasciatus. Infection rates for WNV.IC and SLEV-prME/WNV.IC were significantly lower than SLEV.IC and WNV-prME/SLEV.IC infection rates. These results indicated that WNV and SLEV oral infectivities are not mediated by genetic differences within the prM and E proteins. PMID:25157120

  19. Toll-Like Receptor-3 Is Dispensable for the Innate MicroRNA Response to West Nile Virus (WNV)

    PubMed Central

    Chugh, Pauline E.; Damania, Blossom A.; Dittmer, Dirk P.

    2014-01-01

    The innate immune response to West Nile virus (WNV) infection involves recognition through toll-like receptors (TLRs) and RIG-I-like receptors (RLRs), leading to establishment of an antiviral state. MiRNAs (miRNAs) have been shown to be reliable biomarkers of TLR activation. Here, we sought to evaluate the contribution of TLR3 and miRNAs to the host response to WNV infection. We first analyzed HEK293-NULL and HEK293-TLR3 cells for changes in the innate immune response to infection. The presence of TLR3 did not seem to affect WNV load, infectivity or phosphorylation of IRF3. Analysis of experimentally validated NFκB-responsive genes revealed a WNV-induced signature largely independent of TLR3. Since miRNAs are involved in viral pathogenesis and the innate response to infection, we sought to identify changes in miRNA expression upon infection in the presence or absence of TLR3. MiRNA profiling revealed 70 miRNAs induced following WNV infection in a TLR3-independent manner. Further analysis of predicted gene targets of WNV signature miRNAs revealed genes highly associated with pathways regulating cell death, viral pathogenesis and immune cell trafficking. PMID:25127040

  20. Exposure of resident sparrows to West Nile virus evidenced in South Tunisia.

    PubMed

    Hammouda, A; Lecollinet, S; Hamza, F; Nasri, I; Neb, A; Selmi, S

    2015-12-01

    During the last few years, several cases of West Nile virus (WNV) infection in humans have been reported in Tunisia. However, detailed information on WNV infection in wild birds, the primary amplifying host of WNV, are lacking. In this work, we investigated the exposure of wild sparrows (hybrid Passer domesticus × hispaniolensis) living in two oases in southern Tunisia (Gabès and Kébili oases) to WNV, through the detection of WNV-specific antibodies by using ELISA and microneutralization tests. In total, 208 birds were sampled (54 from Kébili, 154 from Gabès). Anti-WNV antibodies were detected in two birds, corresponding to an overall seroprevalence of 1%. There was no significant difference between the two sampled populations [1·85% (1/54) in Kébili, 0·65% (1/154) in Gabès]. These data provide indirect evidence of the exposure of resident sparrows in southern Tunisia to WNV.

  1. Protective efficacy of a recombinant subunit West Nile virus vaccine in domestic geese (Anser anser)

    USGS Publications Warehouse

    Jarvi, S.I.; Lieberman, M.M.; Hofmeister, E.; Nerurkar, V.R.; Wong, T.; Weeks-Levy, C.

    2008-01-01

    Introduction of the West Nile virus (WNV) to Hawai'i will undoubtedly devastate many populations of critically endangered avian species indigenous to Hawai'i. The protective efficacy of a protein-based WNV subunit vaccine formulated with adjuvant was evaluated in domestic geese as a surrogate species for the endangered Ne??ne??, the state bird of Hawai'i. Prevention of viremia following viral infection of vaccinated birds was used as the clinical endpoint of protection. ELISA and plaque reduction neutralization tests demonstrate that significant levels of vaccine antigen-specific antibody were produced in groups of birds vaccinated with 5 or 10 ??g of the WN-80E antigen formulated with ISA720 adjuvant. Moreover, after challenge with WNV, no viremia was detected in vaccinated birds, whereas viremia was detected up to 4 days after and virus was detected by oral swab for 6 days after infection among control groups. Safe and effective vaccination of managed or captive endangered bird populations will protect species with critically low numbers that could not survive the added mortality of introduced disease. ?? 2008 Elsevier Ltd.

  2. Splenic macrophages are required for protective innate immunity against West Nile virus

    PubMed Central

    Bryan, Marianne A.; Giordano, Daniela; Draves, Kevin E.; Green, Richard; Gale, Michael

    2018-01-01

    Although the spleen is a major site for West Nile virus (WNV) replication and spread, relatively little is known about which innate cells in the spleen replicate WNV, control viral dissemination, and/or prime innate and adaptive immune responses. Here we tested if splenic macrophages (MΦs) were necessary for control of WNV infection. We selectively depleted splenic MΦs, but not draining lymph node MΦs, by injecting mice intravenously with clodronate liposomes several days prior to infecting them with WNV. Mice missing splenic MΦs succumbed to WNV infection after an increased and accelerated spread of virus to the spleen and the brain. WNV-specific Ab and CTL responses were normal in splenic MΦ-depleted mice; however, numbers of NK cells and CD4 and CD8 T cells were significantly increased in the brains of infected mice. Splenic MΦ deficiency led to increased WNV in other splenic innate immune cells including CD11b- DCs, newly formed MΦs and monocytes. Unlike other splenic myeloid subsets, splenic MΦs express high levels of mRNAs encoding the complement protein C1q, the apoptotic cell clearance protein Mertk, the IL-18 cytokine and the FcγR1 receptor. Splenic MΦ-deficient mice may be highly susceptible to WNV infection in part to a deficiency in C1q, Mertk, IL-18 or Caspase 12 expression. PMID:29408905

  3. Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine.

    PubMed

    Poore, Elizabeth A; Slifka, Dawn K; Raué, Hans-Peter; Thomas, Archana; Hammarlund, Erika; Quintel, Benjamin K; Torrey, Lindsay L; Slifka, Ariel M; Richner, Justin M; Dubois, Melissa E; Johnson, Lawrence P; Diamond, Michael S; Slifka, Mark K; Amanna, Ian J

    2017-01-05

    West Nile virus (WNV) is a mosquito-transmitted pathogen with a wide geographical range that can lead to long-term disability and death in some cases. Despite the public health risk posed by WNV, including an estimated 3 million infections in the United States alone, no vaccine is available for use in humans. Here, we present a scaled manufacturing approach for production of a hydrogen peroxide-inactivated whole virion WNV vaccine, termed HydroVax-001WNV. Vaccination resulted in robust virus-specific neutralizing antibody responses and protection against WNV-associated mortality in mice or viremia in rhesus macaques (RM). A GLP-compliant toxicology study performed in rats demonstrated an excellent safety profile with clinical findings limited to minor and transient irritation at the injection site. An in vitro relative potency (IVRP) assay was developed and shown to correlate with in vivo responses following forced degradation studies. Long-term in vivo potency comparisons between the intended storage condition (2-8°C) and a thermally stressed condition (40±2°C) demonstrated no loss in vaccine efficacy or protective immunity over a 6-month span of time. Together, the positive pre-clinical findings regarding immunogenicity, safety, and stability indicate that HydroVax-001WNV is a promising vaccine candidate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Development and evaluation of a new epitope-blocking ELISA for universal detection of antibodies to West Nile virus.

    PubMed

    Sotelo, Elena; Llorente, Francisco; Rebollo, Belen; Camuñas, Ana; Venteo, Angel; Gallardo, Carmina; Lubisi, Alison; Rodríguez, María José; Sanz, Antonio J; Figuerola, Jordi; Jiménez-Clavero, Miguel Ángel

    2011-06-01

    West Nile virus (WNV) is an emerging zoonotic pathogen with a wide range of hosts, including birds, horses and humans. The development and evaluation of the performance of a new enzyme-linked immunosorbent assay (ELISA) are described for rapid detection of WNV-specific antibodies in samples originating from an extensive range of vertebrates susceptible to WNV infection. The assay uses a monoclonal antibody (MAb) which binds whole virus particles and neutralizes infection in vitro by recognizing a neutralizing epitope within the envelope (E) glycoprotein of the virus. This MAb, labelled with horseradish peroxidase, was used to compete with WNV-specific serum antibodies for virus-binding in vitro. The epitope-blocking ELISA was optimized in a manner that enabled its validation with a number of experimental and field sera, from a wide range of wild bird species, and susceptible mammals. The new ELISA exhibited high specificity (79.5-96.5%) and sensitivity (100%), using the virus-neutralization test as reference standard. It also required a much lower volume of sample (10 μl per analysis) compared to other ELISAs available commercially. This new method may be helpful for diagnosis and disease surveillance, particularly when testing samples from small birds, which are available in limited amounts. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Modeling Dynamics of Culex pipiens Complex Populations and Assessing Abatement Strategies for West Nile Virus

    PubMed Central

    Pawelek, Kasia A.; Hager, Elizabeth J.; Hunt, Gregg J.

    2014-01-01

    The primary mosquito species associated with underground stormwater systems in the United States are the Culex pipiens complex species. This group represents important vectors of West Nile virus (WNV) throughout regions of the continental U.S. In this study, we designed a mathematical model and compared it with surveillance data for the Cx. pipiens complex collected in Beaufort County, South Carolina. Based on the best fit of the model to the data, we estimated parameters associated with the effectiveness of public health insecticide (adulticide) treatments (primarily pyrethrin products) as well as the birth, maturation, and death rates of immature and adult Cx. pipiens complex mosquitoes. We used these estimates for modeling the spread of WNV to obtain more reliable disease outbreak predictions and performed numerical simulations to test various mosquito abatement strategies. We demonstrated that insecticide treatments produced significant reductions in the Cx. pipiens complex populations. However, abatement efforts were effective for approximately one day and the vector mosquitoes rebounded until the next treatment. These results suggest that frequent insecticide applications are necessary to control these mosquitoes. We derived the basic reproductive number (ℜ0) to predict the conditions under which disease outbreaks are likely to occur and to evaluate mosquito abatement strategies. We concluded that enhancing the mosquito death rate results in lower values of ℜ0, and if ℜ0<1, then an epidemic will not occur. Our modeling results provide insights about control strategies of the vector populations and, consequently, a potential decrease in the risk of a WNV outbreak. PMID:25268229

  6. Spatial Risk Assessments Based on Vector-Borne Disease Epidemiologic Data: Importance of Scale for West Nile Virus Disease in Colorado

    PubMed Central

    Winters, Anna M.; Eisen, Rebecca J.; Delorey, Mark J.; Fischer, Marc; Nasci, Roger S.; Zielinski-Gutierrez, Emily; Moore, Chester G.; Pape, W. John; Eisen, Lars

    2010-01-01

    We used epidemiologic data for human West Nile virus (WNV) disease in Colorado from 2003 and 2007 to determine 1) the degree to which estimates of vector-borne disease occurrence is influenced by spatial scale of data aggregation (county versus census tract), and 2) the extent of concordance between spatial risk patterns based on case counts versus incidence. Statistical analyses showed that county, compared with census tract, accounted for approximately 50% of the overall variance in WNV disease incidence, and approximately 33% for the subset of cases classified as West Nile neuroinvasive disease. These findings indicate that sub-county scale presentation provides valuable risk information for stakeholders. There was high concordance between spatial patterns of WNV disease incidence and case counts for census tract (83%) but not for county (50%) or zip code (31%). We discuss how these findings impact on practices to develop spatial epidemiologic data for vector-borne diseases and present data to stakeholders. PMID:20439980

  7. Newcastle disease virus-vectored West Nile fever vaccine is immunogenic in mammals and poultry.

    PubMed

    Wang, Jinliang; Yang, Jie; Ge, Jinying; Hua, Ronghong; Liu, Renqiang; Li, Xiaofeng; Wang, Xijun; Shao, Yu; Sun, Encheng; Wu, Donglai; Qin, Chengfeng; Wen, Zhiyuan; Bu, Zhigao

    2016-06-24

    West Nile virus (WNV) is an emerging zoonotic pathogen which is harmful to human and animal health. Effective vaccination in susceptible hosts should protect against WNV infection and significantly reduce viral transmission between animals and from animals to humans. A versatile vaccine suitable for different species that can be delivered via flexible routes remains an essential unmet medical need. In this study, we developed a recombinant avirulent Newcastle disease virus (NDV) LaSota strain expressing WNV premembrane/envelope (PrM/E) proteins (designated rLa-WNV-PrM/E) and evaluated its immunogenicity in mice, horses, chickens, ducks and geese. Mouse immunization experiments disclosed that rLa-WNV-PrM/E induces significant levels of WNV-neutralizing antibodies and E protein-specific CD4+ and CD8+ T-cell responses. Moreover, recombinant rLa-WNV-PrM/E elicited significant levels of WNV-specific IgG in horses upon delivery via intramuscular immunization, and in chickens, ducks and geese via intramuscular, oral or intranasal immunization. Our results collectively support the utility of rLa-WNV-PrM/E as a promising WNV veterinary vaccine candidate for mammals and poultry.

  8. Avian diversity and West Nile virus: Testing associations between biodiversity and infectious disease risk

    USGS Publications Warehouse

    Ezenwa, V.O.; Godsey, M.S.; King, R.J.; Guptill, S.C.

    2006-01-01

    The emergence of several high profile infectious diseases in recent years has focused attention on our need to understand the ecological factors contributing to the spread of infectious diseases. West Nile virus (WNV) is a mosquito-borne zoonotic disease that was first detected in the United States in 1999. The factors accounting for variation in the prevalence of WNV are poorly understood, but recent ideas suggesting links between high biodiversity and reduced vector-borne disease risk may help account for distribution patterns of this disease. Since wild birds are the primary reservoir hosts for WNV, we tested associations between passerine (Passeriform) bird diversity, non-passerine (all other orders) bird diversity and virus infection rates in mosquitoes and humans to examine the extent to which bird diversity is associated with WNV infection risk. We found that non-passerine species richness (number of non-passerine species) was significantly negatively correlated with both mosquito and human infection rates, whereas there was no significant association between passerine species richness and any measure of infection risk. Our findings suggest that non-passerine diversity may play a role in dampening WNV amplification rates in mosquitoes, minimizing human disease risk. ?? 2005 The Royal Society.

  9. Avian diversity and West Nile virus: testing associations between biodiversity and infectious disease risk.

    USGS Publications Warehouse

    Ezenwa, V.O.; Godsey, M.S.; King, R.J.; Guptill, S.C.

    2006-01-01

    The emergence of several high profile infectious diseases in recent years has focused attention on our need to understand the ecological factors contributing to the spread of infectious diseases. West Nile virus (WNV) is a mosquito-borne zoonotic disease that was first detected in the United States in 1999. The factors accounting for variation in the prevalence of WNV are poorly understood, but recentideas suggesting links between high biodiversity and reduced vector-borne disease risk may help account for distribution patterns of this disease. Since wild birds are the primary reservoir hosts for WNV, we tested associations between passerine (Passeriform) bird diversity, non-passerine (all other orders) bird diversity and virus infection rates in mosquitoes and humans to examine the extent to which bird diversity is associated with WNV infection risk. We found t h at non-passerine species richness (number of non-passerine species) was significantly negatively correlated with both mosquito and human infection rates, whereas there was no significant association between passerine species richness and any measure of infection risk. Our findings suggest that non-passerine diversity may play a role in dampening WNV amplification rates in mosquitoes, minimizing human disease risk.

  10. Real time PCR assay for detection of all known lineages of West Nile virus.

    PubMed

    Vázquez, Ana; Herrero, Laura; Negredo, Anabel; Hernández, Lourdes; Sánchez-Seco, María Paz; Tenorio, Antonio

    2016-10-01

    West Nile virus (WNV) is one of the most widespread arbovirus and a large variety of WNV strains and lineages have been described. The molecular methods for the diagnosis of WNV target mainly lineages 1 and 2, which have caused outbreaks in humans, equines and birds. But the last few years new and putative WNV lineages of unknown pathogenicity have been described. Here we describe a new sensitive and specific real-time PCR assay for the detection and quantification of all the WNV lineages described until now. Primers and probe were designed in the 3'-untranslated region (3'-UTR) of the WNV genome and were designed to match all sequenced WNV strains perfectly. The sensitivity of the assay ranged from 1,5 to 15 copies per reaction depending on the WNV lineage tested. The method was validated for WNV diagnosis using different viral strains, human samples (cerebrospinal fluid, biopsies, serum and plasma) and mosquito pools. The assay did not amplify any other phylogenetically or symptomatically related viruses. All of the above make it a very suitable tool for the diagnosis of WNV and for surveillance studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Prospective investigation of the impact of West Nile Virus infections in renal diseases.

    PubMed

    Ergunay, Koray; Karagul, Aydan; Abudalal, Ayman; Hacioglu, Sabri; Us, Durdal; Erdem, Yunus; Ozkul, Aykut

    2015-10-01

    An increased incidence of chronic kidney disease (CKD) after West Nile Virus (WNV) infections has been suggested but the association of WNV infections with renal damage remain inconclusive. This study was undertaken to characterize WNV infections in individuals with acute kidney injury (AKI) and CKD, and to evaluate hemodialysis as a probable transmission route. A total of 463 plasma and urine samples were collected from 45 AKI and 77 CKD patients. Nested and real-time polymerase chain reaction (PCR) assays were employed for viral RNA detection. Specific immunoglobulins were investigated via immunofluorescence and plaque reduction neutralization assays. Consecutive pre and post-dialysis samples were evaluated in CKD cases. WNV RNA and specific immunoglobulins were detected in 7 (5.7%) and 5 (4.1%) individuals, respectively. The AKI patients with WNV RNA in blood and urine had underlying diseases requiring immunosuppressive therapy and demonstrated moderate to high viral loads. No clinical symptom related to WNV infection were observed in CKD cases with detectable viral nucleic acids. All WNV sequences were characterized as lineage 1 clade 1a and several amino acid substitutions with unknown impact were noted. Detailed epidemiologic investigation of WNV RNA positive CKD cases revealed probable vector-borne virus exposure, without the evidence for transmission via hemodialysis. © 2015 Wiley Periodicals, Inc.

  12. ANALYSIS OF BIOTIC AND ABIOTIC FACTORS INFLUENCING THE OCCURRENCE OF WEST NILE VIRUS INFECTION IN TUNISIA.

    PubMed

    Ben Hassine, Th; Calistri, P; Ippoliti, C; Conte, A; Danzetta, M L; Bruno, R; Lelli, R; Bejaoui, M; Hammami, S

    2014-01-01

    Eco-climatic conditions are often associated with the occurrence of West Nile Disease (WND) cases. Among the complex set of biotic and abiotic factors influencing the emergence and spread of this vector-borne disease, two main variables have been considered to have a great influence on the probability of West Nile Virus (WNV) introduction and circulation in Tunisia: the presence of susceptible bird populations and the existence of geographical areas where the environmental and climatic conditions are more favourable to mosquito multiplications. The aim of this study was to identify and classify the climatic and environmental variables possibly associated with the occurrence of WNVhuman cases in Tunisia. The following environmental and climatic variables have been considered: wetlands and humid areas, Normalised Difference Vegetation Index (NDVI), temperatures and elevation. A preliminary analysis for the characterization of main variables associated with areas with a history of WNV human cases in Tunisia between 1997 and 2011 has been made. This preliminary analysis clearly indicates the closeness to marshes ecosystem, where migratory bird populations are located, as an important risk factor for WNV infection. On the contrary the temperature absolute seems to be not a significant factor in Tunisian epidemiological situation. In relation to NDVI values, more complex considerations should be made.

  13. West Nile Virus NS1 Antagonizes Interferon Beta Production by Targeting RIG-I and MDA5.

    PubMed

    Zhang, Hong-Lei; Ye, Han-Qing; Liu, Si-Qing; Deng, Cheng-Lin; Li, Xiao-Dan; Shi, Pei-Yong; Zhang, Bo

    2017-09-15

    West Nile virus (WNV) is a mosquito-borne flavivirus that causes epidemics of encephalitis and viscerotropic disease worldwide. This virus has spread rapidly and has posed a significant public health threat since the outbreak in New York City in 1999. The interferon (IFN)-mediated antiviral response represents an important component of virus-host interactions and plays an essential role in regulating viral replication. Previous studies have suggested that multifunctional nonstructural proteins encoded by flaviviruses antagonize the host IFN response via various means in order to establish efficient viral replication. In this study, we demonstrated that the nonstructural protein 1 (NS1) of WNV antagonizes IFN-β production, most likely through suppression of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) activation. In a dual-luciferase reporter assay, WNV NS1 significantly inhibited the activation of the IFN-β promoter after Sendai virus infection or poly(I·C) treatment. NS1 also suppressed the activation of the IFN-β promoter when it was stimulated by interferon regulatory factor 3 (IRF3)/5D or its upstream molecules in the RLR signaling pathway. Furthermore, NS1 blocked the phosphorylation and nuclear translocation of IRF3 upon stimulation by various inducers. Mechanistically, WNV NS1 targets RIG-I and melanoma differentiation-associated gene 5 (MDA5) by interacting with them and subsequently causing their degradation by the proteasome. Furthermore, WNV NS1 inhibits the K63-linked polyubiquitination of RIG-I, thereby inhibiting the activation of downstream sensors in the RLR signaling pathway. Taken together, our results reveal a novel mechanism by which WNV NS1 interferes with the host antiviral response. IMPORTANCE WNV Nile virus (WNV) has received increased attention since its introduction to the United States. However, the pathogenesis of this virus is poorly understood. This study demonstrated that the nonstructural protein 1 (NS1) of WNV

  14. The Impact of Cycling Temperature on the Transmission of West Nile Virus.

    PubMed

    Danforth, Mary E; Reisen, William K; Barker, Christopher M

    2016-05-01

    West Nile virus (WNV) is an important cause of disease in humans and animals. Risk of WNV infection varies seasonally, with the greatest risk during the warmest parts of the year due in part to the accelerated extrinsic incubation rate of the virus in mosquitoes. Rates of extrinsic incubation have been shown in constant-temperature studies to increase as an approximately linear function of temperature, but for other vector-borne pathogens, such as malaria or dengue virus, nonlinear relationships have been demonstrated under cycling temperatures near the thermal limits of pathogen replication. Using typical daily air temperature profiles from three key periods of WNV amplification in a hyperendemic area of WNV activity in California's Central Valley, as well as a fourth temperature profile based on exposures that would result from daily mosquito host-seeking and resting behavior, we explored the impacts of cycling temperatures on WNV transmission by Culex tarsalis Coquillett, one of the principal vectors in the western United States. The daily cycling temperature ranges studied were representative of those that occur across much of California, but they did not significantly alter the extrinsic incubation period of WNV compared with estimates from mean temperatures alone. This suggests that within the relatively broad range we studied, WNV incubation rates are a simple function of mean temperature. Realistic daily temperature patterns that reflected mosquitoes' avoidance of daytime high temperatures during summer reduced transmission over time compared with air temperatures, indicating that adjustment for mosquito exposure temperatures would be prudent for calculating risk. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Fatal hemorrhagic fever caused by West Nile virus in the United States.

    PubMed

    Paddock, Christopher D; Nicholson, William L; Bhatnagar, Julu; Goldsmith, Cynthia S; Greer, Patricia W; Hayes, Edward B; Risko, Joseph A; Henderson, Corey; Blackmore, Carina G; Lanciotti, Robert S; Campbell, Grant L; Zaki, Sherif R

    2006-06-01

    Most West Nile virus (WNV) infections in humans are asymptomatic; severe disease occurs in relatively few patients and typically manifests as encephalitis, meningitis, or acute flaccid paralysis. A few cases of life-threatening disease with diffuse hemorrhagic manifestations have been reported in Africa; however, this clinical presentation has not been documented for any of the >16,700 cases of WNV disease reported in the United States during 1999-2004. We describe a case of fulminant WNV infection in a 59-year-old Florida man who died following a brief illness that resembled hemorrhagic disease caused by Rickettsia reckettsii, dengue virus or yellow fever virus. Traditional and contemporary diagnostic assays, including culture isolation, electron microscopic examination, reverse-transcriptase polymerase chain reaction amplification, and immunohistochemical stains, were used to confirm systemic WNV infection in the patient. WNV was isolated in a cell culture from a skin biopsy specimen obtained from the patient shortly prior to death. Electron microscopic examination identified the isolate as a flavivirus, and reverse-transcriptase polymerase chain reaction amplified specific WNV sequences from the isolate and patient tissue. Quantitative polymerase chain reaction identified approximately 1x10(7) viral copies/mL in the patient's serum. WNV antigens were detected by immunohistochemical stains in intravascular mononuclear cells and endothelium in skin, lung, liver, kidney, spleen, bone marrow, and central nervous system; no viral antigens were identified in neurons or glial cells of the central nervous system. Although hemorrhagic disease is a rare manifestation of WNV infection, the findings provided by this report may offer new insights regarding the clinical spectrum and pathogenesis of WNV disease in humans.

  16. Conserved amino acids within the N-terminus of the West Nile virus NS4A protein contribute to virus replication, protein stability and membrane proliferation.

    PubMed

    Ambrose, R L; Mackenzie, J M

    2015-07-01

    The West Nile virus strain Kunjin virus (WNVKUN) NS4A protein is a multifunctional protein involved in many aspects of the virus life-cycle and is a major component of the WNVKUN replication complex (RC). Previously we identified a conserved region in the C-terminus of NS4A regulating proteolytic processing and RC assembly, and now investigate key conserved residues in the N-terminus of NS4A and their contribution to WNVKUN replication. Mutation of P13 completely ablated replication, whereas, mutation of P48 and D49, near the first transmembrane helix, and G66 within the helix, showed variable defects in replication, virion secretion and membrane proliferation. Intriguingly, the P48 and G66 NS4A mutants resulted in specific proteasome depletion of NS4A that could in part be rescued with a proteasome inhibitor. Our results suggest that the N-terminus of NS4A contributes to correct folding and stability, essential for facilitating the essential roles of NS4A during replication. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Co-circulation of West Nile virus and distinct insect-specific flaviviruses in Turkey.

    PubMed

    Ergünay, Koray; Litzba, Nadine; Brinkmann, Annika; Günay, Filiz; Sarıkaya, Yasemen; Kar, Sırrı; Örsten, Serra; Öter, Kerem; Domingo, Cristina; Erisoz Kasap, Özge; Özkul, Aykut; Mitchell, Luke; Nitsche, Andreas; Alten, Bülent; Linton, Yvonne-Marie

    2017-03-20

    Active vector surveillance provides an efficient tool for monitoring the presence or spread of emerging or re-emerging vector-borne viruses. This study was undertaken to investigate the circulation of flaviviruses. Mosquitoes were collected from 58 locations in 10 provinces across the Aegean, Thrace and Mediterranean Anatolian regions of Turkey in 2014 and 2015. Following morphological identification, mosquitoes were pooled and screened by nested and real-time PCR assays. Detected viruses were further characterised by sequencing. Positive pools were inoculated onto cell lines for virus isolation. Next generation sequencing was employed for genomic characterisation of the isolates. A total of 12,711 mosquito specimens representing 15 species were screened in 594 pools. Eleven pools (2%) were reactive in the virus screening assays. Sequencing revealed West Nile virus (WNV) in one Culex pipiens (s.l.) pool from Thrace. WNV sequence corresponded to lineage one clade 1a but clustered distinctly from the Turkish prototype isolate. In 10 pools, insect-specific flaviviruses were characterised as Culex theileri flavivirus in 5 pools of Culex theileri and one pool of Cx. pipiens (s.l.), Ochlerotatus caspius flavivirus in two pools of Aedes (Ochlerotatus) caspius, Flavivirus AV-2011 in one pool of Culiseta annulata, and an undetermined flavivirus in one pool of Uranotaenia unguiculata from the Aegean and Thrace regions. DNA forms or integration of the detected insect-specific flaviviruses were not observed. A virus strain, tentatively named as "Ochlerotatus caspius flavivirus Turkey", was isolated from an Ae. caspius pool in C6/36 cells. The viral genome comprised 10,370 nucleotides with a putative polyprotein of 3,385 amino acids that follows the canonical flavivirus polyprotein organisation. Sequence comparisons and phylogenetic analyses revealed the close relationship of this strain with Ochlerotatus caspius flavivirus from Portugal and Hanko virus from Finland. Several

  18. Explaining and forecasting interannual variability in the flow of the Nile River

    NASA Astrophysics Data System (ADS)

    Siam, M. S.; Eltahir, E. A. B.

    2014-05-01

    The natural interannual variability in the flow of Nile River had a significant impact on the ancient civilizations and cultures that flourished on the banks of the river. This is evident from stories in the Bible and Koran, and from the numerous Nilometers discovered near ancient temples. Here, we analyze extensive data sets collected during the 20th century and define four modes of natural variability in the flow of Nile River, identifying a new significant potential for improving predictability of floods and droughts. Previous studies have identified a significant teleconnection between the Nile flow and the Eastern Pacific Ocean. El Niño-Southern Oscillation (ENSO) explains about 25% of the interannual variability in the Nile flow. Here, we identify, for the first time, a region in the southern Indian Ocean with similarly strong teleconnection to the Nile flow. Sea Surface Temperature (SST) in the region (50-80° E and 25-35° S) explains 28% of the interannual variability in the Nile flow. During those years with anomalous SST conditions in both Oceans, we estimate that indices of the SSTs in the Pacific and Indian Oceans can collectively explain up to 84% of the interannual variability in the flow of Nile. Building on these findings, we use classical Bayesian theorem to develop a new hybrid forecasting algorithm that predicts the Nile flow based on global models predictions of indices of the SST in the Eastern Pacific and Southern Indian Oceans.

  19. The E glycoprotein plays an essential role in the high pathogenicity of European-Mediterranean IS98 strain of West Nile virus.

    PubMed

    Alsaleh, Khaled; Khou, Cécile; Frenkiel, Marie-Pascale; Lecollinet, Sylvie; Vàzquez, Ana; de Arellano, Eva Ramírez; Després, Philippe; Pardigon, Nathalie

    2016-05-01

    West Nile virus (WNV) is the most widespread arbovirus in the world. Several recent outbreaks and epizootics have been reported in Europe and the Mediterranean basin with increased virulence. In contrast to the well-characterized American and Australian strains, little is known about the virulence determinants of the WNV European-Mediterranean strains. To investigate the viral factors involved in the virulence of these strains, we generated chimeras between the highly neuropathogenic Israel 1998 (IS-98-ST1, IS98) strain and the non-pathogenic Malaysian Kunjin virus (KJMP-502). In vivo analyses in a mouse model of WNV pathogenesis shows that chimeric virus where KJMP-502 E glycoprotein was replaced by that of IS98 is neuropathogenic, demonstrating that this protein is a major virulence determinant. Presence of the N-glycosylation site had limited impact on virus virulence and the 5'UTR does not seem to influence pathogenesis. Finally, mice inoculated with KJMP-502 virus were protected against lethal IS98 infection. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Outdoor Hazards & Preventive Measures: West Nile Virus: A Clinical Commentary for the Camp Health Care Community; Poison Ivy: A Primer for Prevention; Lyme Disease Prevention and Control.

    ERIC Educational Resources Information Center

    Reynolds, Ellen; Bauer, Holly; Ratner-Connolly, Heidi

    2003-01-01

    Transmitted by mosquitos, West Nile virus may cause serious illness, but the actual likelihood of infection is low. Prevention, implications, and recommendations for camps are discussed. Poison ivy identification, treatment, and complications are presented; a prevention quiz is included. Signs and symptoms of Lyme disease are described, as are…