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.

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...

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...

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...

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...

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...

Evaluation of a mouse model for the West Nile virus group for the purpose of determining viral pathotypes.

PubMed

Bingham, John; Payne, Jean; Harper, Jennifer; Frazer, Leah; Eastwood, Sarah; Wilson, Susanne; Lowther, Sue; Lunt, Ross; Warner, Simone; Carr, Mary; Hall, Roy A; Durr, Peter A

2014-06-01

West Nile virus (WNV; family Flaviviridae; genus Flavivirus) group members are an important cause of viral meningoencephalitis in some areas of the world. They exhibit marked variation in pathogenicity, with some viral lineages (such as those from North America) causing high prevalence of severe neurological disease, whilst others (such as Australian Kunjin virus) rarely cause disease. The aim of this study was to characterize WNV disease in a mouse model and to elucidate the pathogenetic features that distinguish disease variation. Tenfold dilutions of five WNV strains (New York 1999, MRM16 and three horse isolates of WNV-Kunjin: Boort and two isolates from the 2011 Australian outbreak) were inoculated into mice by the intraperitoneal route. All isolates induced meningoencephalitis in different proportions of infected mice. WNVNY99 was the most pathogenic, the three horse isolates were of intermediate pathogenicity and WNVKUNV-MRM16 was the least, causing mostly asymptomatic disease with seroconversion. Infectivity, but not pathogenicity, was related to challenge dose. Using cluster analysis of the recorded clinical signs, histopathological lesions and antigen distribution scores, the cases could be classified into groups corresponding to disease severity. Metrics that were important in determining pathotype included neurological signs (paralysis and seizures), meningoencephalitis, brain antigen scores and replication in extra-neural tissues. Whereas all mice infected with WNVNY99 had extra-neural antigen, those infected with the WNV-Kunjin viruses only occasionally had antigen outside the nervous system. We conclude that the mouse model could be a useful tool for the assessment of pathotype for WNVs. © 2014 CSIRO.

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.

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.

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.

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

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.

Mumps Meningoencephalitis, Toronto, 1963

PubMed Central

McLean, D. M.; Bach, Ruth D.; Larke, R. P. B.; McNaughton, G. A.

1964-01-01

Between January and June 1963, 45 children were hospitalized with mumps meningoencephalitis. Of 39 patients with laboratory evidence of mumps infection, 24 had parotitis and 15 showed no salivary gland involvement. Cerebrospinal fluids from 18 of 40 patients yielded mumps virus by inoculation of rhesus monkey kidney cultures; 33 subjects, including 12 of the 18 virus excretors, showed rising or elevated levels of mumps antihemagglutinin during convalescence. Between May 1959 and June 1963, mumps virus was recovered from cerebrospinal fluids of 50 of 126 cases of mumps meningoencephalitis; virus isolation rates were highest during the peak incidence of mumps meningoencephalitis in winter and early spring. Mumps vaccine (inactivated) was administered to 34 parents with no history of mumps, shortly after their children developed mumps. Mumps occurred in three of 17 parents without prevaccination mumps antihemagglutinins, and in two others, but in none of 15 who had prevaccination antibodies. PMID:14120950

MUMPS MENINGOENCEPHALITIS, TORONTO, 1963.

PubMed

MCLEAN, D M; BACH, R D; LARKE, R P; MCNAUGHTON, G A

1964-02-15

Between January and June 1963, 45 children were hospitalized with mumps meningoencephalitis. Of 39 patients with laboratory evidence of mumps infection, 24 had parotitis and 15 showed no salivary gland involvement. Cerebrospinal fluids from 18 of 40 patients yielded mumps virus by inoculation of rhesus monkey kidney cultures; 33 subjects, including 12 of the 18 virus excretors, showed rising or elevated levels of mumps antihemagglutinin during convalescence. Between May 1959 and June 1963, mumps virus was recovered from cerebrospinal fluids of 50 of 126 cases of mumps meningoencephalitis; virus isolation rates were highest during the peak incidence of mumps meningoencephalitis in winter and early spring.Mumps vaccine (inactivated) was administered to 34 parents with no history of mumps, shortly after their children developed mumps. Mumps occurred in three of 17 parents without prevaccination mumps antihemagglutinins, and in two others, but in none of 15 who had prevaccination antibodies.

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.

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.

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.

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

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

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.

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

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.

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.

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

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.

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

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.

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

[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.

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.

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

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

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.

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

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.

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.

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

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.

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

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...

Electrodiagnostic features of acute paralytic poliomyelitis associated with West Nile virus infection.

PubMed

Al-Shekhlee, Amer; Katirji, Bashar

2004-03-01

West Nile virus (WNV) infection is a potentially fatal disease, with meningoencephalitis being its most common neurological manifestation. Guillain-Barré syndrome (GBS) has also been described, but acute paralytic poliomyelitis has only recently been recognized. We report the clinical and electrodiagnostic findings of five patients with WNV infection, who presented with acute paralytic poliomyelitis. Three patients manifested focal asymmetrical weakness, and two had rapid ascending quadriplegia mimicking GBS. Electrodiagnostic studies during the acute illness showed normal sensory nerve action potentials, compound motor action potentials of normal or reduced amplitude, and no slowing of nerve conduction velocities. Depending on the timing of the examination, fibrillation potentials were widespread, including in those with focal weakness. Cervical magnetic resonance imaging in one patient showed abnormal T2-weighted signals in the spinal cord gray matter. On follow-up, signs of clinical improvement were seen in one patient, whereas two remained quadriplegic and ventilator-dependent 5 months after the onset. This report highlights the value of the electrodiagnostic studies in the diagnosis and prognosis of focal or generalized weakness due to acute paralytic poliomyelitis associated with WNV infection.

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

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.

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.

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

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

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.

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.

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

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

Amoebic meningoencephalitis in Samarinda East Kalimantan

NASA Astrophysics Data System (ADS)

Siagian, L. R. D.; Toruan, V. M. L.; Hutahaen, Y. O.; Gunawan, C.

2018-04-01

Meningoencephalitis is a disease of central nervous system caused by s microorganism such as bacteria, Rickettsiae, Spirochaeta, virus, fungus, protozoa and helminth. Free living amoeba protozoa has been reported as an etiology agent of menigoencephalitis. Amoebic meningoencephalitis is a very rare condition and often fatal because of late diagnosis. We reported a 24 years old woman, hospitalized at Abdul Wahab Syahranie’s Hospital, Samarinda East Kalimantan with decreased of consciousness and fever. The brain MRI showed focal lession suggested as a granuloma. ed Microorganisms like cyst and trophozoit with pseudopodia amoeboic form were identified from the cerebrospinal fluid. Based on these findings the patient was diagnosed with amoebic meningoencephalitis infection and got intravenous metronidazole. The patient died on the twenty third days of hospitalization..

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.

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

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

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.

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

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.

Late Ebola virus relapse causing meningoencephalitis: a case report.

PubMed

Jacobs, Michael; Rodger, Alison; Bell, David J; Bhagani, Sanjay; Cropley, Ian; Filipe, Ana; Gifford, Robert J; Hopkins, Susan; Hughes, Joseph; Jabeen, Farrah; Johannessen, Ingolfur; Karageorgopoulos, Drosos; Lackenby, Angie; Lester, Rebecca; Liu, Rebecca S N; MacConnachie, Alisdair; Mahungu, Tabitha; Martin, Daniel; Marshall, Neal; Mepham, Stephen; Orton, Richard; Palmarini, Massimo; Patel, Monika; Perry, Colin; Peters, S Erica; Porter, Duncan; Ritchie, David; Ritchie, Neil D; Seaton, R Andrew; Sreenu, Vattipally B; Templeton, Kate; Warren, Simon; Wilkie, Gavin S; Zambon, Maria; Gopal, Robin; Thomson, Emma C

2016-07-30

There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2). A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach. On admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus. Our report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors

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

Key role of T cell defects in age-related vulnerability to West Nile virus.

PubMed

Brien, James D; Uhrlaub, Jennifer L; Hirsch, Alec; Wiley, Clayton A; Nikolich-Zugich, Janko

2009-11-23

West Nile virus (WNV) infection causes a life-threatening meningoencephalitis that becomes increasingly more prevalent over the age of 50 and is 40-50x more prevalent in people over the age of 70, compared with adults under the age of 40. In a mouse model of age-related vulnerability to WNV, we demonstrate that death correlates with increased viral titers in the brain and that this loss of virus control with age was the result of defects in the CD4 and CD8 T cell response against WNV. Specific age-related defects in T cell responses against dominant WNV epitopes were detected at the level of cytokine and lytic granule production, each of which are essential for resistance against WNV, and in the ability to generate multifunctional anti-WNV effector T cells, which are believed to be critical for robust antiviral immunity. In contrast, at the peak of the response, old and adult T cells exhibited superimposable peptide sensitivity. Most importantly, although the adult CD4 or CD8 T cells readily protected immunodeficient mice upon adoptive transfer, old T cells of either subset were unable to provide WNV-specific protection. Consistent with a profound qualitative and quantitative defect in T cell immunity, old brains contained at least 12x fewer total effector CD8 T cells compared with adult mice at the peak of brain infection. These findings identify potential targets for immunomodulation and treatment to combat lethal WNV infection in the elderly.

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

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.

Toscana Virus Genome Stability: Data from a Meningoencephalitis Case in Mantua, Italy

PubMed Central

Baggieri, Melissa; Gattuso, Gianni; Fortuna, Claudia; Remoli, Maria Elena; Vaccari, Gabriele; Zaccaria, Guendalina; Marchi, Antonella; Bucci, Paola; Benedetti, Eleonora; Fiorentini, Cristiano; Nicoletti, Loredana

2014-01-01

Abstract In July of 2013, samples from a patient with a neurological syndrome were collected from Mantua hospital and sent to the National Reference Laboratory for Arboviruses (National Institute of Health, Rome). On the basis of the symptoms, serological and molecular assays were performed to diagnose either West Nile virus (WNV) or Toscana virus (TOSV) infection. Molecular and serological tests confirmed TOSV infection. Virus isolation was obtained from cerebrospinal fluid. A full genome sequence was determined from this TOSV strain with next-generation sequencing using Ion Torrent technology. Nucleotide and amino acidic sequences grouped phylogenetically with lineage TOSV A and showed a low genome variability. PMID:25514123

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.

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

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.

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.

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

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.

[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.

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 ...

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

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

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.

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.

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.

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

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

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.

Powassan meningoencephalitis, New York, New York, USA.

PubMed

Sung, Simon; Wurcel, Alysse G; Whittier, Susan; Kulas, Karen; Kramer, Laura D; Flam, Robin; Roberts, James Kirkland; Tsiouris, Simon

2013-01-01

Disease caused by Powassan virus (POWV), a tick-borne flavivirus, ranges from asymptomatic to severe neurologic compromise and death. Two cases of POWV meningoencephalitis in New York, USA, highlight diagnostic techniques, neurologic outcomes, and the effect of POWV on communities to which it is endemic.

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.

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

Powassan Meningoencephalitis, New York, New York, USA

PubMed Central

Wurcel, Alysse G.; Whittier, Susan; Kulas, Karen; Kramer, Laura D.; Flam, Robin; Roberts, James Kirkland; Tsiouris, Simon

2013-01-01

Disease caused by Powassan virus (POWV), a tick-borne flavivirus, ranges from asymptomatic to severe neurologic compromise and death. Two cases of POWV meningoencephalitis in New York, USA, highlight diagnostic techniques, neurologic outcomes, and the effect of POWV on communities to which it is endemic. PMID:23969017

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

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

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

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).

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.

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

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

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. ...

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.

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.

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

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.

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.

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

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

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.

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.

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.

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

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.

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.

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.

Usutu virus: an emerging flavivirus in Europe.

PubMed

Ashraf, Usama; Ye, Jing; Ruan, Xindi; Wan, Shengfeng; Zhu, Bibo; Cao, Shengbo

2015-01-19

Usutu virus (USUV) is an African mosquito-borne flavivirus belonging to the Japanese encephalitis virus serocomplex. USUV is closely related to Murray Valley encephalitis virus, Japanese encephalitis virus, and West Nile virus. USUV was discovered in South Africa in 1959. In Europe, the first true demonstration of circulation of USUV was reported in Austria in 2001 with a significant die-off of Eurasian blackbirds. In the subsequent years, USUV expanded to neighboring countries, including Italy, Germany, Spain, Hungary, Switzerland, Poland, England, Czech Republic, Greece, and Belgium, where it caused unusual mortality in birds. In 2009, the first two human cases of USUV infection in Europe have been reported in Italy, causing meningoencephalitis in immunocompromised patients. This review describes USUV in terms of its life cycle, USUV surveillance from Africa to Europe, human cases, its cellular tropism and pathogenesis, its genetic relationship with other flaviviruses, genetic diversity among USUV strains, its diagnosis, and a discussion of the potential future threat to Asian countries.

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.

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...

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

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.

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

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.

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.

DNA vaccines encoding the envelope protein of West Nile virus lineages 1 or 2 administered intramuscularly, via electroporation and with recombinant virus protein induce partial protection in large falcons (Falco spp.).

PubMed

Fischer, Dominik; Angenvoort, Joke; Ziegler, Ute; Fast, Christine; Maier, Kristina; Chabierski, Stefan; Eiden, Martin; Ulbert, Sebastian; Groschup, Martin H; Lierz, Michael

2015-08-17

As West Nile virus (WNV) can cause lethal diseases in raptors, a vaccination prophylaxis of free-living and captive populations is desirable. In the absence of vaccines approved for birds, equine vaccines have been used in falcons, but full protection against WNV infection was not achieved. Therefore, two DNA vaccines encoding the ectodomain of the envelope protein of WNV lineages 1 and 2, respectively, were evaluated in 28 large falcons. Four different vaccination protocols were used, including electroporation and booster-injections of recombinant WNV domain III protein, before challenge with the live WNV lineage 1 strain NY99. Drug safety, plasmid shedding and antibody production were monitored during the vaccination period. Serological, virological, histological, immunohistochemical and molecular biological investigations were performed during the challenge trials. Antibody response following vaccination was low overall and lasted for a maximum of three weeks. Plasmid shedding was not detected at any time. Viremia, mortality and levels, but not duration, of oral virus shedding were reduced in all of the groups during the challenge trial compared to the non-vaccinated control group. Likewise, clinical scoring, levels of cloacal virus shedding and viral load in organs were significantly reduced in three vaccination groups. Histopathological findings associated with WNV infections (meningo-encephalitis, myocarditis, and arteritis) were present in all groups, but immunohistochemical detection of the viral antigen was reduced. In conclusion, the vaccines can be used safely in falcons to reduce mortality and clinical signs and to lower the risk of virus transmission due to decreased levels of virus shedding and viremia, but full protection was not achieved in all groups.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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

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

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.

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.

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

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.

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

[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.

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.

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.

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.

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...

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.

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

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

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...

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.

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.

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.

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...

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.

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.

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.

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

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.

[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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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

Isolation and molecular identification of Naegleria fowleri from Nile river, Egypt.

PubMed

Al-Herrawy, Ahmad Z; Gad, Mahmoud A

2015-12-01

Members of the genus Naegleria are free-living amoebae distributed in various aquatic environments. Naegleria fowleri is the only species that can cause fatal primary amoebic meningoencephalitis in humans. A total of 48 Nile water samples were collected from the water stream passing though Cairo. The samples were processed for the detection of Naegleria spp. using non-nutrient agar at 45°C. The isolates of Naegleria spp. were identified based on the morphologic criteria of trophozoite, flagellated and cyst stages. Molecular characterization of the isolates was performed using PCR. The obtained results showed that Naegleria spp. were found in 45.8% of Nile water samples by means of microscopic examination. Seasonally, the highest prevalence of Naegleria spp. was recorded in summer (66.7%). Moreover, the highest prevalence of N. fowleri was recorded in summer (25%). The occurrence of heat-tolerant Naegleria spp., especially N. fowleri, in Nile water should be considered as a potential health threat.

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.

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.

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

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.

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.

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

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

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.

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

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.

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.

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.

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

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...

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.

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

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.

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.

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

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.

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.

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.

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.

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 (...

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

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.

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...

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.

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.

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.

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.

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

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.

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

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

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

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.

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.

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.

[Metalloproteinases in meningoencephalitis].

PubMed

Pastuszka, Ewa; Pabin, Agata; Radkowski, Marek

2008-01-01

Meningoencephalitis remains a devastating disease with high morbidity and mortality. Despite advances in antibiotic treatment and critical care, mortality rate in bacterial meningoencephalitis is close to 25%. Moreover, neurological and neuropsychological sequelae emerge in up to 50% of survivors. Adverse outcome is significantly associated with events secondary to meningitis and damage of the blood-brain barrier. Several studies conducted on animals confirmed that matrix-metalloproteinases (MMP), a family of enzymes with major actions in the remodeling of exracellural matrix components facilitate this process which results in acute neurological complications. Gelatinases (MMP-2, MMP-9), the most complex family member, through degradation of gelatine and collagen IV play an important role in the pathogenesis of brain's inflamatory diseases (e.g. Guillian-Barre syndrom) and contribute to spreading the disease beyond the central nervous system. Infection (bacterial, viral or fungal) can lead to increased concentration and activity of metalloproteinases due to excessive enzyme's secretion or decrease in level of its natural inhibitors. A detailed analysis of those enzymes could help in developing new diagnostic and prognostic markers for meningoencephalitis and could facilitate new treatment approaches.

Recombinant canine distemper virus strain Snyder Hill expressing green or red fluorescent proteins causes meningoencephalitis in the ferret.

PubMed

Ludlow, M; Nguyen, D T; Silin, D; Lyubomska, O; de Vries, R D; von Messling, V; McQuaid, S; De Swart, R L; Duprex, W P

2012-07-01

The propensity of canine distemper virus (CDV) to spread to the central nervous system is one of the primary features of distemper. Therefore, we developed a reverse genetics system based on the neurovirulent Snyder Hill (SH) strain of CDV (CDV(SH)) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (CSF) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. The use of recombinant CDV(SH) (rCDV(SH)) expressing enhanced green fluorescent protein (EGFP) or red fluorescent protein (dTomato) facilitated the sensitive pathological assessment of routes of virus spread in vivo. Infection of ferrets with these viruses led to the full spectrum of clinical signs typically associated with distemper in dogs during a rapid, fatal disease course of approximately 2 weeks. Comparison with the ferret-adapted CDV(5804P) and the prototypic wild-type CDV(R252) showed that hematogenous infection of the choroid plexus is not a significant route of virus spread into the CSF. Instead, viral spread into the subarachnoid space in rCDV(SH)-infected animals was triggered by infection of vascular endothelial cells and the hematogenous spread of virus-infected leukocytes from meningeal blood vessels into the subarachnoid space. This resulted in widespread infection of cells of the pia and arachnoid mater of the leptomeninges over large areas of the cerebral hemispheres. The ability to sensitively assess the in vivo spread of a neurovirulent strain of CDV provides a novel model system to study the mechanisms of virus spread into the CSF and the pathogenesis of acute viral meningitis.

Recombinant Canine Distemper Virus Strain Snyder Hill Expressing Green or Red Fluorescent Proteins Causes Meningoencephalitis in the Ferret

PubMed Central

Ludlow, M.; Nguyen, D. T.; Silin, D.; Lyubomska, O.; de Vries, R. D.; von Messling, V.; McQuaid, S.; De Swart, R. L.

2012-01-01

The propensity of canine distemper virus (CDV) to spread to the central nervous system is one of the primary features of distemper. Therefore, we developed a reverse genetics system based on the neurovirulent Snyder Hill (SH) strain of CDV (CDVSH) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (CSF) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. The use of recombinant CDVSH (rCDVSH) expressing enhanced green fluorescent protein (EGFP) or red fluorescent protein (dTomato) facilitated the sensitive pathological assessment of routes of virus spread in vivo. Infection of ferrets with these viruses led to the full spectrum of clinical signs typically associated with distemper in dogs during a rapid, fatal disease course of approximately 2 weeks. Comparison with the ferret-adapted CDV5804P and the prototypic wild-type CDVR252 showed that hematogenous infection of the choroid plexus is not a significant route of virus spread into the CSF. Instead, viral spread into the subarachnoid space in rCDVSH-infected animals was triggered by infection of vascular endothelial cells and the hematogenous spread of virus-infected leukocytes from meningeal blood vessels into the subarachnoid space. This resulted in widespread infection of cells of the pia and arachnoid mater of the leptomeninges over large areas of the cerebral hemispheres. The ability to sensitively assess the in vivo spread of a neurovirulent strain of CDV provides a novel model system to study the mechanisms of virus spread into the CSF and the pathogenesis of acute viral meningitis. PMID:22553334

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

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...

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

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

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

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

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

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.

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.

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.

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.

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

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.

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

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.

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

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.

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...

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

Meningitis and Meningoencephalitis among Israel Defense Force Soldiers: 20 Years Experience at the Hadassah Medical Centers.

PubMed

Pikkel, Yoav Y; Ben-Hur, Tamir; Eliahou, Ruth; Honig, Asaf

2015-11-01

Meningitis and meningoencephalitis pose major risks of morbidity and mortality. To describe 20 years of experience treating infections of the central nervous system in Israel Defense Force (IDF) soldiers, including the common presentations, pathogens and sequelae, and to identify risk groups among soldiers. All soldiers who were admitted to the Hadassah University Medical Center (both campuses: Ein Kerem and Mt. Scopus) due to meningitis and meningoencephalitis from January 1993 to January 2014 were included in this retrospective study. Clinical, laboratory and radiologic data were reviewed from their hospital and army medical corps files. Attention was given to patients' military job description, i.e., combat vs. non-combat soldier, soldiers in training, and medical personnel. We identified 97 cases of suspected meningitis or meningoencephalitis. Six were mistakenly filed and these patients were found to have other disorders. Four soldiers were diagnosed with epidural abscess and five with meningitis due to non-infectious in flammatory diseases. Eighty-two soldiers in active and reserve duty had infectious meningitis or meningoencephalitis. Of these, 46 (56.1%) were combat soldiers and 31 (37.8%) non-combat; 20 (29.2%) were soldiers in training, 10 (12.2%) were training staff and 8 (9.8%) were medical staff. The main pathogens were enteroviruses, Epstein-Barr virus an d Neisseria meningitidis. In our series, soldiers in training, combat soldiers and medical personnel had meningitis and meningoencephalitis more than other soldiers. Enteroviruses are highly infectious pathogens and can cause outbreaks. N. meningitidis among IDF soldiers is still a concern. Early and aggressive treatment with steroids should be considered especially in robust meningoencephalitis cases.

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.

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

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...

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.

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

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

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.

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.

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.

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...

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

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.

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.

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.

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

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

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.

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

Fatal Case of Deer Tick Virus Encephalitis

PubMed Central

Tavakoli, Norma P.; Wang, Heng; Dupuis, Michelle; Hull, Rene; Ebel, Gregory D.; Gilmore, Emily J.; Faust, Phyllis L.

2010-01-01

SUMMARY Deer tick virus is related to Powassan virus, a tickborne encephalitis virus. A 62-year-old man presented with a meningoencephalitis syndrome and eventually died. Analyses of tissue samples obtained during surgery and at autopsy revealed a widespread necrotizing meningoencephalitis. Nucleic acid was extracted from formalin-fixed tissue, and the presence of deer tick virus was verified on a flavivirus-specific polymerase-chain-reaction (PCR) assay, followed by sequence confirmation. Immunohistochemical analysis with antisera specific for deer tick virus identified numerous immunoreactive neurons, with prominent involvement of large neurons in the brain stem, cerebellum, basal ganglia, thalamus, and spinal cord. This case demonstrates that deer tick virus can be a cause of fatal encephalitis. PMID:19439744

Fatal case of deer tick virus encephalitis.

PubMed

Tavakoli, Norma P; Wang, Heng; Dupuis, Michelle; Hull, Rene; Ebel, Gregory D; Gilmore, Emily J; Faust, Phyllis L

2009-05-14

Deer tick virus is related to Powassan virus, a tickborne encephalitis virus. A 62-year-old man presented with a meningoencephalitis syndrome and eventually died. Analyses of tissue samples obtained during surgery and at autopsy revealed a widespread necrotizing meningoencephalitis. Nucleic acid was extracted from formalin-fixed tissue, and the presence of deer tick virus was verified on a flavivirus-specific polymerase-chain-reaction (PCR) assay, followed by sequence confirmation. Immunohistochemical analysis with antisera specific for deer tick virus identified numerous immunoreactive neurons, with prominent involvement of large neurons in the brain stem, cerebellum, basal ganglia, thalamus, and spinal cord. This case demonstrates that deer tick virus can be a cause of fatal encephalitis. 2009 Massachusetts Medical Society

Mapping the serological prevalence rate of West Nile fever in equids, Tunisia.

PubMed

Bargaoui, R; Lecollinet, S; Lancelot, R

2015-02-01

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 Tunisia, two outbreaks of WNF occurred in humans in 1997 and 2003; sporadic cases were reported on several other years. Small-scale serological surveys revealed the presence of antibodies against WN virus (WNV) in equid sera. However, clinical cases were never reported in equids, although their population is abundant in Tunisia. This study was achieved to characterize the nationwide serological status of WNV in Tunisian equids. In total, 1189 sera were collected in 2009 during a cross-sectional survey. Sera were tested for IgG antibodies, using ELISA and microneutralization tests. The estimated overall seroprevalence rate was 28%, 95% confidence interval [22; 34]. The highest rates were observed (i) in the north-eastern governorates (Jendouba, 74%), (ii) on the eastern coast (Monastir, 64%) and (iii) in the lowlands of Chott El Jerid and Chott el Gharsa (Kebili, 58%; Tozeur, 52%). Environmental risk factors were assessed, including various indicators of wetlands, wild avifauna, night temperature and chlorophyllous activity (normalized difference vegetation index: NDVI). Multimodel inference showed that lower distance to ornithological sites and wetlands, lower night-time temperature, and higher NDVI in late spring and late fall were associated with higher serological prevalence rate. The model-predicted nationwide map of WNF seroprevalence rate in Tunisian equids highlighted different areas with high seroprevalence probability. These findings are discussed in the perspective of implementing a better WNF surveillance system in Tunisia. This system might rely on (i) a longitudinal survey of sentinel birds in high-risk areas and time periods for WNV transmission, (ii) investigations of bird die-offs and (iii) syndromic surveillance of equine meningoencephalitis. © 2013 Blackwell Verlag GmbH.

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

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

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.

Co-infection ZIKV and HSV-1 associated with meningoencephalitis: Case report and literature review.

PubMed

Araújo, Paulo S Ramos de; Silva Júnior, Mário L de Mélo; Tenório, Marli; Santos, Fabiana G Torreão Dos

2018-04-24

A man, 26years-old, presented fever, mental confusion and a progressively worsening headache 6days prior to admission. The CSF study was suggestive of meningoencephalitis, the PCR study revealed presence of HSV-1 and ZIKV, while other immunology tests were negative. ZIKV was also identified in serum. The MRI showed temporal lobe hyper-intensity in FLAIR-weight sequence with areas of contrast enhancement and the electroencephalogram showed slow wave activity in such region. Patient was treated with acyclovir and supportive measures and had good clinical outcome at evaluation after 6 months. Neurological spectrum of ZIKV manifestations is wide, but meningoencephalitis is not frequent. Co-infection HSV-1 plus ZIKV was not yet related in humans, but there is increased cellular damage caused by association of ZIKV and herpes virus family infection. ZIKV may facilitate infection or recrudescence by other viruses or cause concurrently neuronal injury by direct or indirect mechanisms. We suggest that clinicians attempt new manifestations related to ZIKV and include this agent in differential diagnosis of neurological diseases even when other agents were identified. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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.

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

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.

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.

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...

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

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

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

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.

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.

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

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.

Toscana virus meningo-encephalitis: an important differential diagnosis for elderly travellers returning from Mediterranean countries.

PubMed

Veater, James; Mehedi, Farhan; Cheung, Chee Kay; Nabarro, Laura; Osborne, Jane; Wong, Nicholas; Wiselka, Martin; Tang, Julian W

2017-08-29

Elderly patients have a long list of differentials for causes of acute confusion and altered consciousness levels, including infectious agents. In addition, elderly, retired patients often have more time to travel for tourism, particularly to exotic, warmer locations. Mediterranean countries such as Spain and Italy are popular holiday destinations for British and other tourists, especially during the winter months. However, these warm climates allow insect vectors to proliferate, increasing the risk of exposure to endemic vectorborne viral infections whilst on vacation. Such infections may not be routinely considered by geriatric medical teams. An 87-year old gentleman presented with a three-day history of worsening confusion, lethargy, ataxia, and fevers following a trip to Spain, where he may have sustained a sandfly bite. By the time of admission, he had a reduced GCS, was hallucinating, and was incontinent of urine and faeces, though blood pressure and heart rate were normal. He also appeared hyperaesthetic, and found even capillary blood sugar testing extremely painful. He had no history of cognitive defect or other neurological conditions. He had been previously independently active, with frequent trips to Spain where he maintained a holiday home. He probably sustained a sandfly bite during this most recent trip, whilst cleaning out a shed. Acute and convalescent sera demonstrated IgG antibodies to Toscana virus at extremely high titres of ≥1:10,000 by immunofluorescence assay, though no Toscana virus RNA was detectable in these sera by the time of presentation. Toscana virus should be included in the differential diagnosis of any patients presenting with meningo-encephalitis who have recently returned from a Mediterranean country. Testing for Toscana virus infection is performed by serological testing on acute/convalescent paired sera, and/or a polymerase chain reaction (PCR) assay on blood or cerebrospinal fluid (CSF) if presenting within 5 days of

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.

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

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

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

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

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.

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

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

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.

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.

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.

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

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

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.

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

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.

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.

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

Resveratrol relieves Angiostrongylus cantonensis - Induced meningoencephalitis by activating sirtuin-1.

PubMed

Chen, An-Chih; Shyu, Ling-Yuh; Hsin, Yue-Loong; Chen, Ke-Min; Lai, Shih-Chan

2017-09-01

Resveratrol, a natural herbal compound found in high levels in grapes and red wine, is frequently used as activator of sirtuin-1. This study investigated the potential function of sirtuin-1 in regulating angiostrongyliasis meningoencephalitis in resveratrol-treated mice. Mice were subjected to meningoencephalitis to study the protective effect of resveratrol against meningoencephalitis and investigate the effects of sirtuin-1 activation on brain. Results demonstrated that sirtuin-1 level decreased in mice with meningoencephalitis and significantly increased in resveratrol-treated mice. Moreover, resveratrol treatment significantly reduced eosinophil counts, p65, Interferon-γ, interleukin (IL)-5, IL-33, and tumor necrosis factor-α levels, matrix metalloproteinase-9 activity, claudin-5 degradation, and blood-brain barrier permeability. By contrast, the anti-inflammatory factor IL-10 was significantly increased in resveratrol-treated mice. Resveratrol treatment was partially beneficial in controlling the pathological processes of angiostrongyliasis meningoencephalitis. The results demonstrate the neuroprotective and anti-inflammatory effects of resveratrol against Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis in mice. Treatment with sirtuin-1 agonist was given within a therapeutic window after A. cantonensis infection. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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

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.

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.

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.

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

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.

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

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.

Unique topographic distribution of greyhound nonsuppurative meningoencephalitis.

PubMed

Terzo, Eloisa; McConnell, J Fraser; Shiel, Robert E; McAllister, Hester; Behr, Sebastien; Priestnall, Simon L; Smith, Ken C; Nolan, Catherine M; Callanan, John J

2012-01-01

Greyhound nonsuppurative meningoencephalitis is an idiopathic breed-associated fatal meningoencephalitis with lesions usually occurring within the rostral cerebrum. This disorder can only be confirmed by postmortem examination, with a diagnosis based upon the unique topography of inflammatory lesions. Our purpose was to describe the magnetic resonance (MR) imaging features of this disease. Four Greyhounds with confirmed Greyhound nonsuppurative meningoencephalitis were evaluated by MR imaging. Lesions predominantly affected the olfactory lobes and bulbs, frontal, and frontotemporal cortical gray matter, and caudate nuclei bilaterally. Fluid attenuation inversion recovery (FLAIR) and T2 weighted spin-echo (T2W) sequences were most useful to assess the nature, severity, extension, and topographic pattern of lesions. Lesions were predominantly T2-hyperintense and T1-isointense with minimal or absent contrast enhancement. © 2012 Veterinary Radiology & Ultrasound.

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.

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.

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

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

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.

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

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

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.

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

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

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.

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

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.

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

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.

Lymphadenopathy and non-suppurative meningo-encephalitis in calves experimentally infected with bovine immunodeficiency-like virus (FL112).

PubMed

Munro, R; Lysons, R; Venables, C; Horigan, M; Jeffrey, M; Dawson, M

1998-08-01

In an experiment on bovine immunodeficiency-like virus (BIV), the virological and serological aspects of which were reported in an earlier paper, three groups (A, B and C) of three calves were inoculated subcutaneously with a recently isolated strain (FL112). For group B and group C, the virus was suspended in milk, and for group C (controls) the viral suspension was subjected to pasteurization before inoculation. The calves were killed for necropsy 12 months later. Clinical assessment revealed subtle ataxia in two group A calves, which took the form of an intermittent "shifting" (from one leg to another) lameness, and palpable enlargement of the pre-scapular lymph nodes in one group B animal. At necropsy, haemal lymph nodes (0.1 to 0.5 cm in diameter), occurring singly, were observed in all animals. However, in groups A and B (but not C), enlarged haemal lymph nodes (< or = 2 cm in diameter) were also seen, occurring singly and in chains; and in one group A animal they occurred in grape-like clusters. In groups A and B (but not C), histopathological examination revealed generalized hyperplastic changes in lymph nodes, especially the haemal lymph nodes. This finding was particularly striking in the two clinically ataxic animals from group A, which also showed a non-suppurative meningo-encephalitis; the latter was possibly the cause of the subtle clinical signs. This study supports previous findings on lymphadenopathy resulting from experimental infection with BIV.

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.

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

Seasonal meningoencephalitis in Holstein cattle caused by Naegleria fowleri.

PubMed

Daft, Barbara M; Visvesvara, Govinda S; Read, Deryck H; Kinde, Hailu; Uzal, Francisco A; Manzer, Michael D

2005-11-01

Primary amoebic meningoencephalitis is a fulminant infection of the human central nervous system caused by Naegleria fowleri, a free-living amoeba that thrives in artificially or naturally heated water. The infection usually is acquired while bathing or swimming in such waters. The portal of entry is the olfactory neuroepithelium. This report describes fatal meningoencephalitis caused by N. fowleri in Holstein cattle that consumed untreated surface water in an area of California where summer temperatures at times exceed 42 degrees C. In the summers of 1998 and 1999, severe multifocal necrosuppurative hemorrhagic meningoencephalitis was observed in brain samples from nine 10-20-month-old heifers with clinical histories of acute central nervous system disease. Olfactory lobes and cerebella were most severely affected. Lesions were also evident in periventricular and submeningeal neuropil as well as olfactory nerves. Naegleria fowleri was demonstrated by immunohistochemistry in brain and olfactory nerve lesions and was isolated from one brain. Even though cultures of drinking water did not yield N. fowleri, drinking water was the likely source of the amoeba. The disease in cattle closely resembles primary amoebic meningoencephalitis in humans. Naegleria meningoencephalitis should be included among differential diagnoses of central nervous system disease in cattle during the summer season in areas with high ambient temperatures.

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

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.

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.

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.

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...

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.

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.

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.

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.

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

[Emerging viral diseases in Europe].

PubMed

Löbermann, M; Gürtler, L G; Eichler-Löbermann, B; Reisinger, E C

2012-04-01

Emergence of viral agents in Europe is influenced by various factors. Climatic changes influencing possible vectors, insufficient vaccination, and travel of man and goods are among the most important reasons to explain these changes. Fever and arthralgia are the leading symptoms in infection with Dengue, Sindbis, or Chikungunya virus. In contrast, tick-born encephalitis (TBE), Toscana, or West Nile virus infections mainly lead to meningo-encephalitis. In Europe, hemorrhagic fever is caused by Crimean Congo and Hanta virus. Protective vaccines are available for emerging viral agents like TBE, influenza and measles. © Georg Thieme Verlag KG Stuttgart · New York.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

Primary Amebic Meningoencephalitis Caused by Naegleria fowleri, Karachi, Pakistan

PubMed Central

Shakoor, Sadia; Beg, Mohammad Asim; Bandea, Rebecca; Sriram, Rama; Noman, Fatima; Ali, Farheen; Visvesvara, Govinda S.; Zafar, Afia

2011-01-01

We report 13 cases of Naegleria fowleri primary amebic meningoencephalitis in persons in Karachi, Pakistan, who had no history of aquatic activities. Infection likely occurred through ablution with tap water. An increase in primary amebic meningoencephalitis cases may be attributed to rising temperatures, reduced levels of chlorine in potable water, or deteriorating water distribution systems. PMID:21291600

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.

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

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

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.

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

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.

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

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

[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.

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.

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.

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

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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...

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 ...

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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

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.

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.

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.

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

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.

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.

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.