Analyze Diet
Veterinary immunology and immunopathology2005; 110(3-4); 229-244; doi: 10.1016/j.vetimm.2005.10.003

Replication of West Nile virus in equine peripheral blood mononuclear cells.

Abstract: A cell model of primary monocytes and other mononuclear cells isolated from equine blood was used to study the kinetics of West Nile virus (WNV) replication in a natural host. West Nile virus has emerged on the North American continent as a significant cause of morbidity and mortality in a wide range of avian and mammalian species. While other flaviviruses are known to infect monocytes and lymphocytes, the ability of WNV to productively replicate in specific immune cells of peripheral blood has not been assessed. In this study, enriched populations of monocytes and lymphocytes as well as purified monocytes, CD4+, CD8+ and B lymphocytes were obtained from equine blood. Productive WNV replication was demonstrated by viral growth curves, quantitative RT-PCR for WNV RNA, and indirect immunofluorescence detection of a non-structural WNV protein. Enriched and purified monocytes consistently supported productive viral replication in blood from nine of nine horses tested while a minor subset of CD4+ lymphocytes supported productive replication in cells from three of the nine horses tested. Peak viral titers of 3.2-6.6 log10 PFU/ml were reached at 6 days post-inoculation (p.i.) and titers were maintained through 10-15 days p.i. Activation of monocytes with bacterial lipopolysaccharide, which resulted in activation of nuclear transcription factor kappaB (NF-kappaB) plus elevation of nitric oxide and type I interferon levels, reduced or eliminated WNV replication. These results suggest that immune cells of the peripheral blood may serve as target cells for initial replication of WNV and may play a role in subsequent viral dissemination. Furthermore, primary equine immune cell cultures represent a potentially useful model of a natural WNV host when testing compounds such as antivirals for use in WNV treatment.
Publication Date: 2005-11-28 PubMed ID: 16310859DOI: 10.1016/j.vetimm.2005.10.003Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explores how the West Nile virus (WNV) replicates in equine blood cells and its potential impact on the immune system. The findings suggest potential for developing new anti-viral treatments.

Research Purpose and Methods

  • This research aimed to understand better the behavior of the West Nile virus (WNV) within a natural host, focusing on the virus’s replication kinetics within mononuclear cells isolated from equine blood. The reason for WNV being the case of study is its significant impact as a cause of sickness and mortality across various bird and mammal species in North America.
  • While it was previously known that other related viruses could infect monocytes and lymphocytes, WNV’s ability to reproduce within specific peripheral blood immune cells had not been assessed; the study aimed to fill this gap in knowledge.
  • The researchers obtained enriched populations of monocytes and lymphocytes, as well as purified monocytes, CD4+, CD8+ and B lymphocytes from equine blood. The WNV replication was demonstrated through viral growth curves, quantitative RT-PCR for WNV RNA, and indirect immunofluorescence detection of a non-structural WNV protein.

Research Findings

  • It was found that enriched and purified monocytes consistently supported productive viral replication in the blood from all nine horses tested.
  • Additionally, a minor subset of CD4+ lymphocytes supported productive replication in cells from three of the nine horses tested.
  • Peak viral titers were reached at six days post-inoculation, and they were maintained for an additional 10-15 days.
  • Activating monocytes with bacterial lipopolysaccharide, resulting in the activation of the nuclear transcription factor kappaB (NF-kappaB), and increasing nitric oxide and type I interferon levels, reduced or eliminated WNV replication.

Implications and Conclusions

  • The findings indicate that the immune cells of the peripheral blood may serve as initial target cells for WNV replication, potentially playing a role in subsequent viral dissemination.
  • The understanding of how the West Nile virus operates within equine blood cells could provide insight into ways to reduce or eliminate the viral proliferation within its host.
  • Furthermore, this study demonstrates how primary equine immune cell cultures could be a useful model when testing antiviral compounds for potential use in WNV treatment.

Cite This Article

APA
Garcia-Tapia D, Loiacono CM, Kleiboeker SB. (2005). Replication of West Nile virus in equine peripheral blood mononuclear cells. Vet Immunol Immunopathol, 110(3-4), 229-244. https://doi.org/10.1016/j.vetimm.2005.10.003

Publication

ISSN: 0165-2427
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 110
Issue: 3-4
Pages: 229-244

Researcher Affiliations

Garcia-Tapia, David
  • Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA.
Loiacono, Christie M
    Kleiboeker, Steven B

      MeSH Terms

      • Animals
      • Antigens, CD / metabolism
      • Cell Adhesion
      • Horses / virology
      • Interferon Type I / metabolism
      • Leukocytes, Mononuclear / metabolism
      • Leukocytes, Mononuclear / virology
      • Lipopolysaccharides
      • NF-kappa B / metabolism
      • Neutralization Tests
      • Nitric Oxide / metabolism
      • Virus Replication
      • West Nile virus / physiology

      Citations

      This article has been cited 28 times.
      1. Rivas J, Dubois A, Blanquer A, Gérardy M, Ziegler U, Groschup MH, Grobet L, Garigliany MM. Tendon-Derived Mesenchymal Stem Cells (TDSCs) as an In Vitro Model for Virological Studies in Wild Birds.. Viruses 2023 Jun 27;15(7).
        doi: 10.3390/v15071455pubmed: 37515142google scholar: lookup
      2. Talmi-Frank D, Byas AD, Murrieta R, Weger-Lucarelli J, Rückert C, Gallichotte EN, Yoshimoto JA, Allen C, Bosco-Lauth AM, Graham B, Felix TA, Brault AC, Ebel GD. Intracellular Diversity of WNV within Circulating Avian Peripheral Blood Mononuclear Cells Reveals Host-Dependent Patterns of Polyinfection.. Pathogens 2023 May 26;12(6).
        doi: 10.3390/pathogens12060767pubmed: 37375457google scholar: lookup
      3. Frank DT, Byas AD, Murrieta R, Weger-Lucarelli J, Rückert C, Gallichotte E, Yoshimoto JA, Allen C, Bosco-Lauth AM, Graham B, Felix TA, Brault A, Ebel GD. Intracellular diversity of WNV within circulating avian peripheral blood mononuclear cells reveals host-dependent patterns of polyinfection.. bioRxiv 2023 Jan 29;.
        doi: 10.1101/2023.01.27.525959pubmed: 36747638google scholar: lookup
      4. Yang S, Huang Y, Shi Y, Bai X, Yang P, Chen Q. Tembusu Virus entering the central nervous system caused nonsuppurative encephalitis without disrupting the blood-brain barrier.. J Virol 2021 Mar 10;95(7).
        doi: 10.1128/JVI.02191-20pubmed: 33472933google scholar: lookup
      5. McDonald EM, Anderson J, Wilusz J, Ebel GD, Brault AC. Zika Virus Replication in Myeloid Cells during Acute Infection Is Vital to Viral Dissemination and Pathogenesis in a Mouse Model.. J Virol 2020 Oct 14;94(21).
        doi: 10.1128/JVI.00838-20pubmed: 32847848google scholar: lookup
      6. Habarugira G, Suen WW, Hobson-Peters J, Hall RA, Bielefeldt-Ohmann H. West Nile Virus: An Update on Pathobiology, Epidemiology, Diagnostics, Control and "One Health" Implications.. Pathogens 2020 Jul 19;9(7).
        doi: 10.3390/pathogens9070589pubmed: 32707644google scholar: lookup
      7. Peng BH, Wang T. West Nile Virus Induced Cell Death in the Central Nervous System.. Pathogens 2019 Nov 1;8(4).
        doi: 10.3390/pathogens8040215pubmed: 31683807google scholar: lookup
      8. Carlin AF, Wen J, Vizcarra EA, McCauley M, Chaillon A, Akrami K, Kim C, Ngono AE, Lara-Marquez ML, Smith DM, Glass CK, Schooley RT, Benner C, Shresta S. A longitudinal systems immunologic investigation of acute Zika virus infection in an individual infected while traveling to Caracas, Venezuela.. PLoS Negl Trop Dis 2018 Dec;12(12):e0007053.
        doi: 10.1371/journal.pntd.0007053pubmed: 30596671google scholar: lookup
      9. Kosch R, Delarocque J, Claus P, Becker SC, Jung K. Gene expression profiles in neurological tissues during West Nile virus infection: a critical meta-analysis.. BMC Genomics 2018 Jul 13;19(1):530.
        doi: 10.1186/s12864-018-4914-4pubmed: 30001706google scholar: lookup
      10. Michlmayr D, Andrade P, Gonzalez K, Balmaseda A, Harris E. CD14(+)CD16(+) monocytes are the main target of Zika virus infection in peripheral blood mononuclear cells in a paediatric study in Nicaragua.. Nat Microbiol 2017 Nov;2(11):1462-1470.
        doi: 10.1038/s41564-017-0035-0pubmed: 28970482google scholar: lookup
      11. Bardina SV, Brown JA, Michlmayr D, Hoffman KW, Sum J, Pletnev AG, Lira SA, Lim JK. Chemokine Receptor Ccr7 Restricts Fatal West Nile Virus Encephalitis.. J Virol 2017 May 15;91(10).
        doi: 10.1128/JVI.02409-16pubmed: 28356527google scholar: lookup
      12. Uddin MJ, Suen WW, Bosco-Lauth A, Hartwig AE, Hall RA, Bowen RA, Bielefeldt-Ohmann H. Kinetics of the West Nile virus induced transcripts of selected cytokines and Toll-like receptors in equine peripheral blood mononuclear cells.. Vet Res 2016 Jun 7;47(1):61.
        doi: 10.1186/s13567-016-0347-8pubmed: 27267361google scholar: lookup
      13. Uddin MJ, Suen WW, Prow NA, Hall RA, Bielefeldt-Ohmann H. West Nile Virus Challenge Alters the Transcription Profiles of Innate Immune Genes in Rabbit Peripheral Blood Mononuclear Cells.. Front Vet Sci 2015;2:76.
        doi: 10.3389/fvets.2015.00076pubmed: 26697438google scholar: lookup
      14. Miner JJ, Diamond MS. Mechanisms of restriction of viral neuroinvasion at the blood-brain barrier.. Curr Opin Immunol 2016 Feb;38:18-23.
        doi: 10.1016/j.coi.2015.10.008pubmed: 26590675google scholar: lookup
      15. Bardina SV, Michlmayr D, Hoffman KW, Obara CJ, Sum J, Charo IF, Lu W, Pletnev AG, Lim JK. Differential Roles of Chemokines CCL2 and CCL7 in Monocytosis and Leukocyte Migration during West Nile Virus Infection.. J Immunol 2015 Nov 1;195(9):4306-18.
        doi: 10.4049/jimmunol.1500352pubmed: 26401006google scholar: lookup
      16. Dietrich EA, Bowen RA, Brault AC. An ex vivo avian leukocyte culture model for West Nile virus infection.. J Virol Methods 2015 Jun 15;218:19-22.
      17. Suen WW, Prow NA, Hall RA, Bielefeldt-Ohmann H. Mechanism of West Nile virus neuroinvasion: a critical appraisal.. Viruses 2014 Jul 18;6(7):2796-825.
        doi: 10.3390/v6072796pubmed: 25046180google scholar: lookup
      18. Detournay O, Morrison DA, Wagner B, Zarnegar B, Wattrang E. Genomic analysis and mRNA expression of equine type I interferon genes.. J Interferon Cytokine Res 2013 Dec;33(12):746-59.
        doi: 10.1089/jir.2012.0130pubmed: 23772953google scholar: lookup
      19. Gamino V, Höfle U. Pathology and tissue tropism of natural West Nile virus infection in birds: a review.. Vet Res 2013 Jun 3;44(1):39.
        doi: 10.1186/1297-9716-44-39pubmed: 23731695google scholar: lookup
      20. Cho H, Diamond MS. Immune responses to West Nile virus infection in the central nervous system.. Viruses 2012 Dec 17;4(12):3812-30.
        doi: 10.3390/v4123812pubmed: 23247502google scholar: lookup
      21. De Filette M, Ulbert S, Diamond M, Sanders NN. Recent progress in West Nile virus diagnosis and vaccination.. Vet Res 2012 Mar 1;43(1):16.
        doi: 10.1186/1297-9716-43-16pubmed: 22380523google scholar: lookup
      22. Lim SM, Koraka P, Osterhaus AD, Martina BE. West Nile virus: immunity and pathogenesis.. Viruses 2011 Jun;3(6):811-28.
        doi: 10.3390/v3060811pubmed: 21994755google scholar: lookup
      23. Arjona A, Wang P, Montgomery RR, Fikrig E. Innate immune control of West Nile virus infection.. Cell Microbiol 2011 Nov;13(11):1648-58.
      24. Daley LP, Kutzler MA, Bennett BW, Smith MC, Glaser AL, Appleton JA. Effector functions of camelid heavy-chain antibodies in immunity to West Nile virus.. Clin Vaccine Immunol 2010 Feb;17(2):239-46.
        doi: 10.1128/CVI.00421-09pubmed: 19955323google scholar: lookup
      25. Xiang J, McLinden JH, Rydze RA, Chang Q, Kaufman TM, Klinzman D, Stapleton JT. Viruses within the Flaviviridae decrease CD4 expression and inhibit HIV replication in human CD4+ cells.. J Immunol 2009 Dec 15;183(12):7860-9.
        doi: 10.4049/jimmunol.0902276pubmed: 19923460google scholar: lookup
      26. Garcia-Tapia D, Hassett DE, Mitchell WJ Jr, Johnson GC, Kleiboeker SB. West Nile virus encephalitis: sequential histopathological and immunological events in a murine model of infection.. J Neurovirol 2007 Apr;13(2):130-8.
        doi: 10.1080/13550280601187185pubmed: 17505981google scholar: lookup
      27. Samuel MA, Diamond MS. Pathogenesis of West Nile Virus infection: a balance between virulence, innate and adaptive immunity, and viral evasion.. J Virol 2006 Oct;80(19):9349-60.
        doi: 10.1128/JVI.01122-06pubmed: 16973541google scholar: lookup
      28. Shrestha B, Wang T, Samuel MA, Whitby K, Craft J, Fikrig E, Diamond MS. Gamma interferon plays a crucial early antiviral role in protection against West Nile virus infection.. J Virol 2006 Jun;80(11):5338-48.
        doi: 10.1128/JVI.00274-06pubmed: 16699014google scholar: lookup