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Frontiers in veterinary science2019; 6; 251; doi: 10.3389/fvets.2019.00251

EHV-1 Pathogenesis: Current in vitro Models and Future Perspectives.

Abstract: Primary infection and pathogenesis of equine herpesvirus type 1 (EHV-1) require an intricate interaction of virus with the mucosal epithelium, mononuclear cells and the vascular endothelium. Studies on EHV-1 have been facilitated by the development of different models that recapitulate the tissue complexity. The available assays can be categorized into (i) models mimicking the epithelium-peripheral blood mononuclear cell (PBMC) interaction, which include mucosal (nasal and vaginal) explants and equine respiratory epithelial cells (EREC) cultures; and (ii) PBMC-endothelium mimicking models, including flow chamber and contact assays. These models have proven their worth in attempts to recapitulate the architecture and complexity, produce data relevant to natural host infection, and reduce animal use due to experiments. Although horse models are still needed for certain experiments, e.g., EHV-1 myeloencephalopathy or vaccination studies, available models can be used to obtain highly valuable data on virus-host tissue interactions. Microfluidic based 3D culture system (e.g., horse-on-a-chip) could be a potential upgraded version of these models for future research.
Publication Date: 2019-07-31 PubMed ID: 31417917PubMed Central: PMC6684782DOI: 10.3389/fvets.2019.00251Google Scholar: Lookup
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  • 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.

The research article focuses on equine herpesvirus type 1 (EHV-1) and existing methods to study its pathogenesis. It mentions different in vitro models that can mimic the interaction of the virus with certain tissues and the ways these models help in studying virus-host tissue interactions.

Current In Vitro Models

The research delves into how current in vitro models are helping to understand the pathogenesis of EHV-1:

  • The models used can be divided into two major categories. The first one is the model that mimics the interaction between the epithelium and peripheral blood mononuclear cell (PBMC). These include nasal and vaginal mucosal explants, and equine respiratory epithelial cells (EREC) cultures.
  • The second type of in vitro models mimic PBMC-endothelium interaction. Methods for this kind of modelling include flow chamber and contact assays.

Importance of These Models

The abstract reflects on the significance of these models:

  • These models can replicate the complex architecture of tissues and produce data that is relevant to natural host infection. This can lead to a better understanding of how EHV-1 behaves and impacts its host.
  • Using these models reduces the reliance on animal models, which falls in line with ethical considerations of reducing animal experimentation. However, the research notes that animal models, specifically horse models, are still required for certain types of studies like vaccination research or studying EHV-1 myeloencephalopathy.

Future Perspectives

The paper also suggests future directions in this field:

  • Proposes the use of 3D culture systems like the horse-on-a-chip model. This could be an upgraded version of the existing models and provide more accurate and detailed data on EHV-1 pathogenesis.

Cite This Article

APA
Kamel M, Pavulraj S, Osterrieder K, Azab W. (2019). EHV-1 Pathogenesis: Current in vitro Models and Future Perspectives. Front Vet Sci, 6, 251. https://doi.org/10.3389/fvets.2019.00251

Publication

ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 6
Pages: 251
PII: 251

Researcher Affiliations

Kamel, Mohamed
  • Institut für Virologie, Zentrum für Infektionsmedizin, Freie Universität Berlin, Berlin, Germany.
  • Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Pavulraj, Selvaraj
  • Institut für Virologie, Zentrum für Infektionsmedizin, Freie Universität Berlin, Berlin, Germany.
Osterrieder, Klaus
  • Institut für Virologie, Zentrum für Infektionsmedizin, Freie Universität Berlin, Berlin, Germany.
Azab, Walid
  • Institut für Virologie, Zentrum für Infektionsmedizin, Freie Universität Berlin, Berlin, Germany.

References

This article includes 41 references
  1. Davison AJ, Eberle R, Ehlers B, Hayward GS, McGeoch DJ, Minson AC, Pellett PE, Roizman B, Studdert MJ, Thiry E. The order Herpesvirales.. Arch Virol 2009;154(1):171-7.
    doi: 10.1007/s00705-008-0278-4pmc: PMC3552636pubmed: 19066710google scholar: lookup
  2. Azab W, Dayaram A, Greenwood AD, Osterrieder N. How Host Specific Are Herpesviruses? Lessons from Herpesviruses Infecting Wild and Endangered Mammals.. Annu Rev Virol 2018 Sep 29;5(1):53-68.
  3. Patel JR, Heldens J. Equine herpesviruses 1 (EHV-1) and 4 (EHV-4)--epidemiology, disease and immunoprophylaxis: a brief review.. Vet J 2005 Jul;170(1):14-23.
    doi: 10.1016/j.tvjl.2004.04.018pubmed: 15993786google scholar: lookup
  4. Ma G, Azab W, Osterrieder N. Equine herpesviruses type 1 (EHV-1) and 4 (EHV-4)--masters of co-evolution and a constant threat to equids and beyond.. Vet Microbiol 2013 Nov 29;167(1-2):123-34.
    doi: 10.1016/j.vetmic.2013.06.018pubmed: 23890672google scholar: lookup
  5. Smith D, Hamblin A, Edington N. Equid herpesvirus 1 infection of endothelial cells requires activation of putative adhesion molecules: an in vitro model.. Clin Exp Immunol 2002 Aug;129(2):281-7.
  6. Goehring LS, Hussey GS, Ashton LV, Schenkel AR, Lunn DP. Infection of central nervous system endothelial cells by cell-associated EHV-1.. Vet Microbiol 2011 Mar 24;148(2-4):389-95.
    doi: 10.1016/j.vetmic.2010.08.030pubmed: 20884134google scholar: lookup
  7. Vandekerckhove AP, Glorieux S, Gryspeerdt AC, Steukers L, Van Doorsselaere J, Osterrieder N, Van de Walle GR, Nauwynck HJ. Equine alphaherpesviruses (EHV-1 and EHV-4) differ in their efficiency to infect mononuclear cells during early steps of infection in nasal mucosal explants.. Vet Microbiol 2011 Aug 26;152(1-2):21-8.
    doi: 10.1016/j.vetmic.2011.03.038pubmed: 21536394google scholar: lookup
  8. Soboll Hussey G, Ashton LV, Quintana AM, Lunn DP, Goehring LS, Annis K, Landolt G. Innate immune responses of airway epithelial cells to infection with equine herpesvirus-1.. Vet Microbiol 2014 May 14;170(1-2):28-38.
    doi: 10.1016/j.vetmic.2014.01.018pubmed: 24560592google scholar: lookup
  9. Spiesschaert B, Goldenbogen B, Taferner S, Schade M, Mahmoud M, Klipp E, Osterrieder N, Azab W. Role of gB and pUS3 in Equine Herpesvirus 1 Transfer between Peripheral Blood Mononuclear Cells and Endothelial Cells: a Dynamic In Vitro Model.. J Virol 2015 Dec;89(23):11899-908.
    doi: 10.1128/JVI.01809-15pmc: PMC4645325pubmed: 26378176google scholar: lookup
  10. Stokol T, Yeo WM, Burnett D, DeAngelis N, Huang T, Osterrieder N, Catalfamo J. Equid herpesvirus type 1 activates platelets.. PLoS One 2015;10(4):e0122640.
  11. Kydd JH, Slater J, Osterrieder N, Lunn DP, Antczak DF, Azab W, Balasuriya U, Barnett C, Brosnahan M, Cook C, Damiani A, Elton D, Frampton A, Gilkerson J, Goehring L, Horohov D, Maxwell L, Minke J, Morley P, Nauwynck H, Newton R, Perkins G, Pusterla N, Soboll-Hussey G, Traub-Dargatz J, Townsend H, Van de Walle GR, Wagner B. Third International Havemeyer Workshop on Equine Herpesvirus type 1.. Equine Vet J 2012 Sep;44(5):513-7.
  12. Vandekerckhove A, Glorieux S, Broeck WV, Gryspeerdt A, van der Meulen KM, Nauwynck HJ. In vitro culture of equine respiratory mucosa explants.. Vet J 2009 Sep;181(3):280-7.
    doi: 10.1016/j.tvjl.2008.03.027pubmed: 18539059google scholar: lookup
  13. Vandekerckhove AP, Glorieux S, Gryspeerdt AC, Steukers L, Duchateau L, Osterrieder N, Van de Walle GR, Nauwynck HJ. Replication kinetics of neurovirulent versus non-neurovirulent equine herpesvirus type 1 strains in equine nasal mucosal explants.. J Gen Virol 2010 Aug;91(Pt 8):2019-2028.
    doi: 10.1099/vir.0.019257-0pubmed: 20427565google scholar: lookup
  14. Baghi HB, Nauwynck HJ. Impact of equine herpesvirus type 1 (EHV-1) infection on the migration of monocytic cells through equine nasal mucosa.. Comp Immunol Microbiol Infect Dis 2014 Dec;37(5-6):321-9.
    doi: 10.1016/j.cimid.2014.09.004pubmed: 25456193google scholar: lookup
  15. Bannazadeh Baghi H, Nauwynck HJ. Effect of equine herpesvirus type 1 (EHV-1) infection of nasal mucosa epithelial cells on integrin alpha 6 and on different components of the basement membrane.. Arch Virol 2016 Jan;161(1):103-10.
    doi: 10.1007/s00705-015-2643-4pubmed: 26497179google scholar: lookup
  16. Van Cleemput J, Poelaert KCK, Laval K, Maes R, Hussey GS, Van den Broeck W, Nauwynck HJ. Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by intercellular junctions.. Sci Rep 2017 Nov 30;7(1):16656.
    doi: 10.1038/s41598-017-16804-5pmc: PMC5709510pubmed: 29192251google scholar: lookup
  17. Negussie H, Li Y, Tessema TS, Nauwynck HJ. Replication characteristics of equine herpesvirus 1 and equine herpesvirus 3: comparative analysis using ex vivo tissue cultures.. Vet Res 2016 Jan 15;47:19.
    doi: 10.1186/s13567-016-0305-5pmc: PMC4714513pubmed: 26768993google scholar: lookup
  18. von Bonsdorff CH, Fuller SD, Simons K. Apical and basolateral endocytosis in Madin-Darby canine kidney (MDCK) cells grown on nitrocellulose filters.. EMBO J 1985 Nov;4(11):2781-92.
  19. Handler JS, Preston AS, Steele RE. Factors affecting the differentiation of epithelial transport and responsiveness to hormones.. Fed Proc 1984 May 15;43(8):2221-4.
    pubmed: 6325248
  20. Rousset M. The human colon carcinoma cell lines HT-29 and Caco-2: two in vitro models for the study of intestinal differentiation.. Biochimie 1986 Sep;68(9):1035-40.
    doi: 10.1016/S0300-9084(86)80177-8pubmed: 3096381google scholar: lookup
  21. Quintana AM, Landolt GA, Annis KM, Hussey GS. Immunological characterization of the equine airway epithelium and of a primary equine airway epithelial cell culture model.. Vet Immunol Immunopathol 2011 Apr 15;140(3-4):226-36.
    doi: 10.1016/j.vetimm.2010.12.008pubmed: 21292331google scholar: lookup
  22. Soboll Hussey G, Ashton LV, Quintana AM, Van de Walle GR, Osterrieder N, Lunn DP. Equine herpesvirus type 1 pUL56 modulates innate responses of airway epithelial cells.. Virology 2014 Sep;464-465:76-86.
    doi: 10.1016/j.virol.2014.05.023pubmed: 25046270google scholar: lookup
  23. Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Soboll Hussey G, Maes RK, Nauwynck HJ. Abortigenic but Not Neurotropic Equine Herpes Virus 1 Modulates the Interferon Antiviral Defense.. Front Cell Infect Microbiol 2018;8:312.
    doi: 10.3389/fcimb.2018.00312pmc: PMC6144955pubmed: 30258819google scholar: lookup
  24. Soboll Hussey G, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP. Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.. Vet Res 2011 Feb 7;42(1):23.
    doi: 10.1186/1297-9716-42-23pmc: PMC3045331pubmed: 21314906google scholar: lookup
  25. Ma G, Feineis S, Osterrieder N, Van de Walle GR. Identification and characterization of equine herpesvirus type 1 pUL56 and its role in virus-induced downregulation of major histocompatibility complex class I.. J Virol 2012 Apr;86(7):3554-63.
    doi: 10.1128/JVI.06994-11pmc: PMC3302497pubmed: 22278226google scholar: lookup
  26. Thormann N, Van de Walle GR, Azab W, Osterrieder N. The role of secreted glycoprotein G of equine herpesvirus type 1 and type 4 (EHV-1 and EHV-4) in immune modulation and virulence.. Virus Res 2012 Oct;169(1):203-11.
  27. Laval K, Favoreel HW, Poelaert KC, Van Cleemput J, Nauwynck HJ. Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a+ Monocytic Cells upon Adhesion to Endothelial Cells.. J Virol 2015 Nov;89(21):10912-23.
    doi: 10.1128/JVI.01589-15pmc: PMC4621108pubmed: 26292328google scholar: lookup
  28. Huh D, Fujioka H, Tung YC, Futai N, Paine R 3rd, Grotberg JB, Takayama S. Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems.. Proc Natl Acad Sci U S A 2007 Nov 27;104(48):18886-91.
    doi: 10.1073/pnas.0610868104pmc: PMC2141877pubmed: 18006663google scholar: lookup
  29. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip.. Science 2010 Jun 25;328(5986):1662-8.
    doi: 10.1126/science.1188302pubmed: 20576885google scholar: lookup
  30. Huh D, Kim HJ, Fraser JP, Shea DE, Khan M, Bahinski A, Hamilton GA, Ingber DE. Microfabrication of human organs-on-chips.. Nat Protoc 2013 Nov;8(11):2135-57.
    doi: 10.1038/nprot.2013.137pubmed: 24113786google scholar: lookup
  31. Stewart MC, Stewart AA. Mesenchymal stem cells: characteristics, sources, and mechanisms of action.. Vet Clin North Am Equine Pract 2011 Aug;27(2):243-61.
    doi: 10.1016/j.cveq.2011.06.004pubmed: 21872757google scholar: lookup
  32. De Schauwer C, Meyer E, Van de Walle GR, Van Soom A. Markers of stemness in equine mesenchymal stem cells: a plea for uniformity.. Theriogenology 2011 May;75(8):1431-43.
  33. Spaas JH, De Schauwer C, Cornillie P, Meyer E, Van Soom A, Van de Walle GR. Culture and characterisation of equine peripheral blood mesenchymal stromal cells.. Vet J 2013 Jan;195(1):107-13.
    doi: 10.1016/j.tvjl.2012.05.006pubmed: 22717781google scholar: lookup
  34. Bussche L, Van de Walle GR. Peripheral Blood-Derived Mesenchymal Stromal Cells Promote Angiogenesis via Paracrine Stimulation of Vascular Endothelial Growth Factor Secretion in the Equine Model.. Stem Cells Transl Med 2014 Dec;3(12):1514-25.
    doi: 10.5966/sctm.2014-0138pmc: PMC4250216pubmed: 25313202google scholar: lookup
  35. Pennington MR, Curtis TM, Divers TJ, Wagner B, Ness SL, Tennant BC, Van de Walle GR. Equine Mesenchymal Stromal Cells from Different Sources Efficiently Differentiate into Hepatocyte-Like Cells.. Tissue Eng Part C Methods 2016 Jun;22(6):596-607.
    doi: 10.1089/ten.tec.2015.0403pubmed: 27113698google scholar: lookup
  36. Smith KC, Mumford JA, Lakhani K. A comparison of equid herpesvirus-1 (EHV-1) vascular lesions in the early versus late pregnant equine uterus.. J Comp Pathol 1996 Apr;114(3):231-47.
    doi: 10.1016/S0021-9975(96)80045-4pubmed: 8762581google scholar: lookup
  37. Wilson WD. Equine herpesvirus 1 myeloencephalopathy.. Vet Clin North Am Equine Pract 1997 Apr;13(1):53-72.
    doi: 10.1016/S0749-0739(17)30255-9pubmed: 9106343google scholar: lookup
  38. Li XJ, Valadez AV, Zuo P, Nie Z. Microfluidic 3D cell culture: potential application for tissue-based bioassays.. Bioanalysis 2012 Jun;4(12):1509-25.
    doi: 10.4155/bio.12.133pmc: PMC3909686pubmed: 22793034google scholar: lookup
  39. Edmondson R, Broglie JJ, Adcock AF, Yang L. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors.. Assay Drug Dev Technol 2014 May;12(4):207-18.
    doi: 10.1089/adt.2014.573pmc: PMC4026212pubmed: 24831787google scholar: lookup
  40. Gupta N, Liu JR, Patel B, Solomon DE, Vaidya B, Gupta V. Microfluidics-based 3D cell culture models: Utility in novel drug discovery and delivery research.. Bioeng Transl Med 2016 Mar;1(1):63-81.
    doi: 10.1002/btm2.10013pmc: PMC5689508pubmed: 29313007google scholar: lookup
  41. Toh YC, Zhang C, Zhang J, Khong YM, Chang S, Samper VD, van Noort D, Hutmacher DW, Yu H. A novel 3D mammalian cell perfusion-culture system in microfluidic channels.. Lab Chip 2007 Mar;7(3):302-9.
    doi: 10.1039/b614872gpubmed: 17330160google scholar: lookup

Citations

This article has been cited 1 times.
  1. Hu Y, Jia Q, Liu J, Sun W, Bao Z, Che C, Wu G, Fan B, Jarhen, Ran D. Molecular characteristics and pathogenicity of an equid alphaherpesvirus 1 strain isolated in China.. Virus Genes 2022 Aug;58(4):284-293.
    doi: 10.1007/s11262-022-01910-ypubmed: 35567668google scholar: lookup