West Nile viral infection of equids

Abstract Microfilariae (MF) are the immature stages of filarial nematode parasites and inhabit the blood and dermis of all classes of vertebrates, except fish. Concurrent ingestion of MF and arboviruses by mosquitoes can enhance mosquito transmission of virus compared to when virus is ingested alone. Shortly after being ingested, MF penetrate the mosquito’s midgut and may introduce virus into the mosquito’s hemocoel, creating a disseminated viral infection much sooner than normal. This phenomenon is known as microfilarial enhancement. Both American Robins and Common Grackles harbor MF—that is, Eufilaria sp. and Chandlerella quiscali von Linstow (Spirurida: Onchocercidae), respectively. We compared infection and dissemination rates in Culex pipiens L. mosquitoes that fed on birds with and without MF infections that had been infected with West Nile virus (WNV). At moderate viremias, about 107 plaque-forming units (pfu)/ml of blood, there were no differences in infection or dissemination rates among mosquitoes that ingested viremic blood from a bird with or without microfilaremia. At high viremias, >108.5 pfu/ml, mosquitoes feeding on a microfilaremic Grackle with concurrent viremia had significantly higher infection and dissemination rates than mosquitoes fed on viremic Grackles without microfilaremia. Microfilarial enhancement depends on the specific virus, MF, and mosquito species examined. How virus is introduced into the hemocoel by MF differs between the avian/WNV systems described here (i.e., leakage) and various arboviruses with MF of the human filarid, Brugia malayi (Brug) (Spirurida: Onchocercidae) (i.e., cotransport). Additional studies are needed to determine if other avian species and their MF are involved in the microfilarial enhancement of WNV in nature.

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THE INFORMATIVE VALUE OF IMMUNOLOGICAL AND GENETIC TESTS IN THE DIAGNOSIS WEST NILE FEVER

Journal of Volgograd State Medical University ◽

10.19163/1994-9480-2020-4(76)-42-45 ◽

2020 ◽

Vol 76 (4) ◽

pp. 42-45

Author(s):

Т.V. Zamarina ◽

◽

N.P. Khrapova ◽

I.A. Barkova ◽

E.V. Pimenova ◽

...

Keyword(s):

Viral Infection ◽

Viral Rna ◽

Unknown Etiology ◽

West Nile Fever ◽

West Nile ◽

Respiratory Viral Infection ◽

Blood Samples ◽

Monitoring Centre ◽

Laboratory Confirmation ◽

Acute Respiratory Viral Infection

We used ELISA and PCR for laboratory verification of West Nile fever (MUC 4.2.3009-12). We analyzed serum and whole blood samples which had been sent to West Nile fever reference monitoring centre in 2018–2019. A total of 270 blood samples obtained from patients with presumed viral encephalitis of unknown etiology, acute respiratory viral infection, acute respiratory viral infection, meningitis, acute gastroenteritis were analyzed. Antibodies against WNV were detected in 193 (71,4 %) blood samples, while 146 samples were found to be capable of developing an immune response with viral RNA not being detected in them. Both WNV antibodies and viral RNA were detected in 47 (17,4 %) samples tested. WNV RNA was detected in only 14 (5,1 %) cases. Thus, laboratory confirmation of WNF was obtained in 76,6 % of cases (207 out of 270).

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Serological evidence of West Nile viral infection in archived swine serum samples from Peninsular Malaysia

Journal of Veterinary Science ◽

10.4142/jvs.2021.22.e29 ◽

2021 ◽

Vol 22 ◽

Author(s):

Mohammed Nma Mohammed ◽

Abd Rahaman Yasmin ◽

Mohd Adzahan Noraniza ◽

Siti Zubaidah Ramanoon ◽

Siti Suri Arshad ◽

...

Keyword(s):

Viral Infection ◽

Peninsular Malaysia ◽

Serological Evidence ◽

Serum Samples ◽

West Nile ◽

Swine Serum

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PATHOLOGY AND EPIDEMIOLOGY OF NATURAL WEST NILE VIRAL INFECTION OF RAPTORS IN GEORGIA

Journal of Wildlife Diseases ◽

10.7589/0090-3558-43.2.214 ◽

2007 ◽

Vol 43 (2) ◽

pp. 214-223 ◽

Cited By ~ 19

Author(s):

Angela E. Ellis ◽

Daniel G. Mead ◽

Andrew B. Allison ◽

David E. Stallknecht ◽

Elizabeth W. Howerth

Keyword(s):

Viral Infection ◽

West Nile

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A Hyperactive Kunjin Virus NS3 Helicase Mutant Demonstrates Increased Dissemination and Mortality in Mosquitoes

Journal of Virology ◽

10.1128/jvi.01021-20 ◽

2020 ◽

Vol 94 (19) ◽

Author(s):

Kelly E. Du Pont ◽

Nicole R. Sexton ◽

Martin McCullagh ◽

Gregory D. Ebel ◽

Brian J. Geiss

Keyword(s):

Cell Culture ◽

Viral Infection ◽

Rna Binding ◽

Nonstructural Protein ◽

Energy Transduction ◽

West Nile ◽

Content Type ◽

Nonstructural Protein 3

ABSTRACT The unwinding of double-stranded RNA intermediates is critical for the replication and packaging of flavivirus RNA genomes. This unwinding activity is achieved by the ATP-dependent nonstructural protein 3 (NS3) helicase. In previous studies, we investigated the mechanism of energy transduction between the ATP and RNA binding pockets using molecular dynamics simulations and enzymatic characterization. Our data corroborated the hypothesis that motif V is a communication hub for this energy transduction. More specifically, mutations T407A and S411A in motif V exhibit a hyperactive helicase phenotype, leading to the regulation of translocation and unwinding during replication. However, the effect of these mutations on viral infection in cell culture and in vivo is not well understood. Here, we investigated the role of motif V in viral replication using West Nile virus (Kunjin subtype) T407A and S411A mutants (T407A and S411A Kunjin, respectively) in cell culture and in vivo. We were able to recover S411A Kunjin but unable to recover T407A Kunjin. Our results indicated that S411A Kunjin decreased viral infection and increased cytopathogenicity in cell culture compared to wild-type (WT) Kunjin. Similarly, decreased infection rates in surviving S411A Kunjin-infected Culex quinquefasciatus mosquitoes were observed, but S411A Kunjin infection resulted in increased mortality compared to WT Kunjin infection. Additionally, S411A Kunjin infection increased viral dissemination and saliva positivity rates in surviving mosquitoes compared to WT Kunjin infection. These data suggest that S411A Kunjin increases viral pathogenesis in mosquitoes. Overall, these data indicate that NS3 motif V may play a role in the pathogenesis, dissemination, and transmission efficiency of Kunjin virus. IMPORTANCE Kunjin and West Nile viruses belong to the arthropod-borne flaviviruses, which can result in severe symptoms, including encephalitis, meningitis, and death. Flaviviruses have expanded into new populations and emerged as novel pathogens repeatedly in recent years, demonstrating that they remain a global threat. Currently, there are no approved antiviral therapeutics against either Kunjin or West Nile viruses. Thus, there is a pressing need for understanding the pathogenesis of these viruses in humans. In this study, we investigated the role of the Kunjin virus helicase on infection in cell culture and in vivo. This work provides new insight into how flaviviruses control pathogenesis and mosquito transmission through the nonstructural protein 3 helicase.

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Interleukin-1β Signaling in Dendritic Cells Induces Antiviral Interferon Responses

mBio ◽

10.1128/mbio.00342-18 ◽

2018 ◽

Vol 9 (2) ◽

Cited By ~ 15

Author(s):

Lauren D. Aarreberg ◽

Courtney Wilkins ◽

Hilario J. Ramos ◽

Richard Green ◽

Michael A. Davis ◽

...

Keyword(s):

Dendritic Cells ◽

West Nile Virus ◽

Virus Infection ◽

Viral Infection ◽

Inflammatory Responses ◽

West Nile Virus Infection ◽

Interleukin 1Β ◽

Effective Control ◽

Immune Control ◽

West Nile

ABSTRACTInduction of interferon beta (IFN-β), IFN-stimulated genes (ISGs), and inflammatory responses is critical for control of viral infection. We recently identified an essential linkage of stimulation of the inflammatory cytokine interleukin-1β (IL-1β) and induction of ISGs that function as host restriction pathways against the emerging flavivirus West Nile virus (WNV)in vivo. Here we utilizedex vivoglobal transcriptome analysis of primary dendritic cells, known targets of WNV replication, to define gene signatures required for this IL-1β-driven antiviral response. Dendritic cells that were deficient in IL-1 receptor signaling showed dysregulation of cell-intrinsic defense genes and loss of viral control during WNV infection. Surprisingly, we found that in wild-type cells, IL-1β treatment, in the absence of infection, drove the transcription of IFN-β and ISGs at late times following treatment. Expression of these antiviral innate immune genes was dependent on the transcription factor IFN regulatory factor 3 (IRF3) and appears to reflect a general shift in IL-1β signaling from an early inflammatory response to a late IFN-mediated response. These data demonstrate that inflammatory and antiviral signals integrate to control viral infection in myeloid cells through a process of IL-1β-to-IRF3 signaling crosstalk. Strategies to exploit these cytokines in the activation of host defense programs should be investigated as novel therapeutic approaches against individual pathogens.IMPORTANCEWest Nile virus is an emerging mosquito-borne flavivirus that can result in serious illness, neuropathology, and death in infected individuals. Currently, there are no vaccines or therapies for human use against West Nile virus. Immune control of West Nile virus infection requires inflammatory and antiviral responses, though the effect that each arm of this response has on the other is unclear. The significance of our research is in defining how virus-induced inflammatory responses regulate critical antiviral immune programs for effective control of West Nile virus infection. These data identify essential mechanisms of immune control that can inform therapeutic efforts against West Nile virus, with potential efficacy against other neuroinvasive viruses.

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Exclusion of West Nile Virus Superinfection through RNA Replication

Journal of Virology ◽

10.1128/jvi.01205-09 ◽

2009 ◽

Vol 83 (22) ◽

pp. 11765-11776 ◽

Cited By ~ 59

Author(s):

Gang Zou ◽

Bo Zhang ◽

Pei-Yin Lim ◽

Zhiming Yuan ◽

Kristen A. Bernard ◽

...

Keyword(s):

West Nile Virus ◽

Viral Infection ◽

Rna Synthesis ◽

Viral Rna ◽

Wild Type Virus ◽

West Nile ◽

Superinfection Exclusion ◽

Mechanistic Analysis ◽

Action Analysis ◽

Nonstructural Genes

ABSTRACT Superinfection exclusion is the ability of an established viral infection to interfere with a second viral infection. Using West Nile virus (WNV) as a model, we show that replicating replicons in BHK-21 cells suppress subsequent WNV infection. The WNV replicon also suppresses superinfections of other flaviviruses but not nonflaviviruses. Mode-of-action analysis indicates that the exclusion of WNV superinfection occurs at the step of RNA synthesis. The continuous culturing of WNV in the replicon-containing cells generated variants that could overcome the superinfection exclusion. The sequencing of the selected viruses revealed mutations in structural (prM S90R or envelope E138K) and nonstructural genes (NS4a K124R and peptide 2K V9M). Mutagenesis analysis showed that the mutations in structural genes nonselectively enhance viral infection in both naïve and replicon-containing BHK-21 cells; in contrast, the mutations in nonstructural genes more selectively enhance viral replication in the replicon-containing cells than in the naïve cells. Mechanistic analysis showed that the envelope mutation functions through the enhancement of virion attachment to BHK-21 cells, whereas the 2K mutation (and, to a lesser extent, the NS4a mutation) functions through the enhancement of viral RNA synthesis. Furthermore, we show that WNV superinfection exclusion is reversible by the treatment of the replicon cells with a flavivirus inhibitor. The preestablished replication of the replicon could be suppressed by infecting the cells with the 2K mutant WNV but not with the wild-type virus. These results suggest that WNV superinfection exclusion is a result of competition for intracellular host factors that are required for viral RNA synthesis.

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A Hyperactive Kunjin Virus NS3 Helicase Mutant Demonstrates Increased Dissemination and Mortality in Mosquitoes

10.1101/2020.05.26.117580 ◽

2020 ◽

Author(s):

Kelly E. Du Pont ◽

Nicole R. Sexton ◽

Martin McCullagh ◽

Gregory D. Ebel ◽

Brian J. Geiss

Keyword(s):

Cell Culture ◽

Viral Infection ◽

Rna Binding ◽

Nonstructural Protein ◽

Transmission Efficiency ◽

Energy Transduction ◽

West Nile ◽

Nonstructural Protein 3

ABSTRACTThe unwinding of double-stranded RNA intermediates is critical for replication and packaging of flavivirus RNA genomes. This unwinding activity is achieved by the ATP-dependent nonstructural protein 3 (NS3) helicase. In previous studies, we investigated the mechanism of energy transduction between the ATP and RNA binding pockets using molecular dynamics simulations and enzymatic characterization. Our data corroborated the hypothesis that Motif V is a communication hub for this energy transduction. More specifically, mutations T407A and S411A in Motif V exhibit a hyperactive helicase phenotype leading to the regulation of translocation and unwinding during replication. However, the effect of these mutations on viral infection in cell culture and in vivo is not well understood. Here, we investigated the role of Motif V in viral replication using T407A and S411A West Nile virus (Kunjin subtype) mutants in cell culture and in vivo. We were able to recover S411A Kunjin but unable to recover T407A Kunjin. Our results indicated that S411A Kunjin decreased viral infection, and increased cytopathogenicity in cell culture as compared to WT Kunjin. Similarly, decreased infection rates in surviving S411A-infected Culex quinquefasciatus mosquitoes were observed, but S411A Kunjin infection resulted in increased mortality compared to WT Kunjin. Additionally, S411A Kunjin increased viral dissemination and saliva positivity rates in surviving mosquitoes compared to WT Kunjin. These data suggest that S411A Kunjin increases pathogenesis in mosquitoes. Overall, these data indicate that NS3 Motif V may play a role in the pathogenesis, dissemination, and transmission efficiency of Kunjin virus.IMPORTANCEKunjin and West Nile viruses belong to the arthropod-borne flaviviruses, which can result in severe symptoms including encephalitis, meningitis, and death. Flaviviruses have expanded into new populations and emerged as novel pathogens repeatedly in recent years demonstrating they remain a global threat. Currently, there are no approved anti-viral therapeutics against either Kunjin or West Nile viruses. Thus, there is a pressing need for understanding the pathogenesis of these viruses in humans. In this study, we investigate the role of the Kunjin virus helicase on infection in cell culture and in vivo. This work provides new insight into how flaviviruses control pathogenesis and mosquito transmission through the nonstructural protein 3 helicase.

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The fight to save Uganda’s White Rhino

Africana Newsletter ◽

10.1017/s0568160x00000125 ◽

1964 ◽

Vol 2 (01) ◽

pp. 6-12

Keyword(s):

The West ◽

West Nile ◽

White Rhino

In the West Nile District of Uganda lives a population of white rhino—those relies of a past age, cumbrous, gentle creatures despite their huge bulk—which estimates only 10 years ago, put at 500. But poachers live in the area, too, and official counts showed that white rhino were being reduced alarmingly. By 1959, they were believed to be diminished to 300.

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West Nile Virus

ASHA Leader ◽

10.1044/leader.ftr5.09092004.10 ◽

2004 ◽

Vol 9 (9) ◽

pp. 10-13

Author(s):

Susan Brady ◽

Rhonda Miserendino ◽

Noel Rao

Keyword(s):

West Nile Virus ◽

West Nile

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