Analyze Diet
Veterinary research2013; 44(1); 118; doi: 10.1186/1297-9716-44-118

Experimental infection with equine herpesvirus type 1 (EHV-1) induces chorioretinal lesions.

Abstract: Equine herpesvirus myeloencephalitis (EHM) remains one of the most devastating manifestations of equine herpesvirus type 1 (EHV-1) infection but our understanding of its pathogenesis remains rudimentary, partly because of a lack of adequate experimental models. EHV-1 infection of the ocular vasculature may offer an alternative model as EHV-1-induced chorioretinopathy appears to occur in a significant number of horses, and the pathogenesis of EHM and ocular EHV-1 may be similar. To investigate the potential of ocular EHV-1 as a model for EHM, and to determine the frequency of ocular EHV-1, our goal was to study: (1) Dissemination of virus following acute infection, (2) Development and frequency of ocular lesions following infection, and (3) Utility of a GFP-expressing virus for localization of the virus in vivo. Viral antigen could be detected following acute infection in ocular tissues and the central nervous system (experiment 1). Furthermore, EHV-1 infection resulted in multifocal choroidal lesions in 90% (experiment 2) and 50% (experiment 3) of experimentally infected horses, however ocular lesions did not appear in vivo until between 3 weeks and 3 months post-infection. Taken together, the timing of the appearance of lesions and their ophthalmoscopic features suggest that their pathogenesis may involve ischemic injury to the chorioretina following viremic delivery of virus to the eye, mirroring the vascular events that result in EHM. In summary, we show that the frequency of ocular EHV-1 is 50-90% following experimental infection making this model attractive for testing future vaccines or therapeutics in an immunologically relevant age group.
Publication Date: 2013-12-05 PubMed ID: 24308772PubMed Central: PMC4028784DOI: 10.1186/1297-9716-44-118Google 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.
  • Evaluation Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 is about understanding the implications of Equine herpesvirus type 1 (EHV-1) on the eye health of horses, and how this knowledge can be utilized to understand the more harmful effects of the same virus on the nervous system of horses.

Understanding the Background and Objective

  • The research takes an in-depth look into the effects of EHV-1, a virus causing equine herpesvirus myeloencephalitis (EHM) in horses, a very serious and devastating condition affecting the nervous system.
  • The researchers identify the need for better understanding of EHM as current knowledge is limited due to inadequate experimental models. They propose the study of EHV-1 infection on the ocular vasculature as an alternative model, since it is seen that the virus induces chorioretinopathy (retina and choroid inflammation) frequently in horses.
  • The ultimate aim is to study the dissemination of the virus post infection, the development and frequency of ocular lesions post infection, and testing the Green Fluorescent Protein (GFP)-expressing virus as a tool to locate the virus.

Key Findings of the Study

  • The researchers found that the viral antigen, which incites an immune response, could be detected in ocular tissues and the central nervous system of the horse post infection.
  • They found that the EHV-1 infection resulted in multifocal choroid lesions in 90% of horses in one experiment and 50% in another. These lesions surprisingly did not appear until the period between 3 weeks and 3 months after infection, suggesting that their development may involve ischemic injury caused by interference with blood supply due to the virus.
  • The timeline of appearance of these lesions, and their features on an ophthalmoscope, indicate their similarity to the vascular events that result in EHM.

Conclusions and Implications

  • The research concludes that the frequency of ocular EHV-1 is between 50 and 90% post experimental infection. This makes it a useful model for creating and testing future vaccines or therapeutic treatments on a relevant age group.
  • Considering that EHV-1 negatively effects horse ocular health and it mirrors the vascular events that result in EHM, understanding the effects of this virus on ocular health can provide insights into the development and consequences of EHM, encouraging further research in this field.

Cite This Article

APA
Hussey GS, Goehring LS, Lunn DP, Hussey SB, Huang T, Osterrieder N, Powell C, Hand J, Holz C, Slater J. (2013). Experimental infection with equine herpesvirus type 1 (EHV-1) induces chorioretinal lesions. Vet Res, 44(1), 118. https://doi.org/10.1186/1297-9716-44-118

Publication

ISSN: 1297-9716
NlmUniqueID: 9309551
Country: England
Language: English
Volume: 44
Issue: 1
Pages: 118

Researcher Affiliations

Hussey, Gisela Soboll
  • Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA. husseygi@msu.edu.
Goehring, Lutz S
    Lunn, David P
      Hussey, Stephen B
        Huang, Teng
          Osterrieder, Nikolaus
            Powell, Cynthia
              Hand, Jesse
                Holz, Carine
                  Slater, Josh

                    MeSH Terms

                    • Animals
                    • Chorioretinitis / epidemiology
                    • Chorioretinitis / pathology
                    • Chorioretinitis / veterinary
                    • Chorioretinitis / virology
                    • Encephalomyelitis / epidemiology
                    • Encephalomyelitis / pathology
                    • Encephalomyelitis / veterinary
                    • Encephalomyelitis / virology
                    • Fluorescein Angiography / methods
                    • Fluorescein Angiography / veterinary
                    • Green Fluorescent Proteins / genetics
                    • Green Fluorescent Proteins / metabolism
                    • Herpesviridae Infections / epidemiology
                    • Herpesviridae Infections / pathology
                    • Herpesviridae Infections / veterinary
                    • Herpesviridae Infections / virology
                    • Herpesvirus 1, Equid / isolation & purification
                    • Horse Diseases / epidemiology
                    • Horse Diseases / pathology
                    • Horse Diseases / virology
                    • Horses
                    • Neutralization Tests / veterinary
                    • Nose / virology
                    • Random Allocation
                    • Viremia / veterinary
                    • Viremia / virology
                    • Virus Shedding

                    References

                    This article includes 34 references
                    1. Allen GP, Kydd JH, Slater JD, Smith KC. Equid herpesvirus 1 and equid herpesvirus 4 infections. Infectious Diseases of Livestock Vol. 44; 2004; pp. 829–859.
                    2. Edington N, Bridges CG, Patel JR. Endothelial cell infection and thrombosis in paralysis caused by equid herpesvirus-1: equine stroke.. Arch Virol 1986;90(1-2):111-24.
                      doi: 10.1007/BF01314149pubmed: 3015074google scholar: lookup
                    3. Goehring LS, van Maanen C, Sloet van Oldruitenborgh-Oosterbaan MM. Neurological syndromes among horses in The Netherlands. A 5 year retrospective survey (1999-2004).. Vet Q 2005 Mar;27(1):11-20.
                      doi: 10.1080/01652176.2005.9695182pubmed: 15835280google scholar: lookup
                    4. Allen GP. Risk factors for development of neurologic disease after experimental exposure to equine herpesvirus-1 in horses.. Am J Vet Res 2008 Dec;69(12):1595-600.
                      doi: 10.2460/ajvr.69.12.1595pubmed: 19046006google scholar: lookup
                    5. 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.
                    6. Paillot R, Daly JM, Luce R, Montesso F, Davis-Poynter N, Hannant D, Kydd JH. Frequency and phenotype of EHV-1 specific, IFN-gamma synthesising lymphocytes in ponies: the effects of age, pregnancy and infection.. Dev Comp Immunol 2007;31(2):202-14.
                      doi: 10.1016/j.dci.2006.05.010pubmed: 16824599google scholar: lookup
                    7. Horohov DW, Kydd JH, Hannant D. The effect of aging on T cell responses in the horse.. Dev Comp Immunol 2002 Jan;26(1):121-8.
                      doi: 10.1016/S0145-305X(01)00027-1pubmed: 11687270google scholar: lookup
                    8. Slater JD, Gibson JS, Barnett KC, Field HJ. Chorioretinopathy associated with neuropathology following infection with equine herpesvirus-1.. Vet Rec 1992 Sep 12;131(11):237-9.
                      pubmed: 1332242doi: 10.1136/vr.131.11.237-agoogle scholar: lookup
                    9. Matthews A. Fundus. 2; 2004.
                    10. House JA, Gregg DA, Lubroth J, Dubovi EJ, Torres A. Experimental equine herpesvirus-1 infection in llamas (Lama glama).. J Vet Diagn Invest 1991 Apr;3(2):137-43.
                      doi: 10.1177/104063879100300206pubmed: 1654133google scholar: lookup
                    11. Rebhun WC, Jenkins DH, Riis RC, Dill SG, Dubovi EJ, Torres A. An epizootic of blindness and encephalitis associated with a herpesvirus indistinguishable from equine herpesvirus I in a herd of alpacas and llamas.. J Am Vet Med Assoc 1988 Apr 1;192(7):953-6.
                      pubmed: 2835346
                    12. Whitwell KE, Blunden AS. Pathological findings in horses dying during an outbreak of the paralytic form of Equid herpesvirus type 1 (EHV-1) infection.. Equine Vet J 1992 Jan;24(1):13-9.
                    13. Sun Y, Brown SM. The open reading frames 1, 2, 71, and 75 are nonessential for the replication of equine herpesvirus type 1 in vitro.. Virology 1994 Mar;199(2):448-52.
                      doi: 10.1006/viro.1994.1143pubmed: 8122373google scholar: lookup
                    14. Crowhurst FA, Dickinson G, Burrows R. An outbreak of paresis in mares and geldings associated with equid herpesvirus 1.. Vet Rec 1981 Dec 12;109(24):527-8.
                      pubmed: 6280366
                    15. Tischer BK, von Einem J, Kaufer B, Osterrieder N. Two-step red-mediated recombination for versatile high-efficiency markerless DNA manipulation in Escherichia coli.. Biotechniques 2006 Feb;40(2):191-7.
                      doi: 10.2144/000112096pubmed: 16526409google scholar: lookup
                    16. Rudolph J, Osterrieder N. Equine herpesvirus type 1 devoid of gM and gp2 is severely impaired in virus egress but not direct cell-to-cell spread.. Virology 2002 Feb 15;293(2):356-67.
                      doi: 10.1006/viro.2001.1277pubmed: 11886256google scholar: lookup
                    17. Gibson JS, Slater JD, Field HJ. The pathogenicity of Ab4p, the sequenced strain of equine herpesvirus-1, in specific pathogen-free foals.. Virology 1992 Jul;189(1):317-9.
                      doi: 10.1016/0042-6822(92)90707-Vpubmed: 1318607google scholar: lookup
                    18. 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
                    19. Gibson JS, Slater JD, Awan AR, Field HJ. Pathogenesis of equine herpesvirus-1 in specific pathogen-free foals: primary and secondary infections and reactivation.. Arch Virol 1992;123(3-4):351-66.
                      doi: 10.1007/BF01317269pubmed: 1314051google scholar: lookup
                    20. Soboll G, Breathnach CC, Kydd JH, Hussey SB, Mealey RM, Lunn DP. Vaccination of ponies with the IE gene of EHV-1 in a recombinant modified live vaccinia vector protects against clinical and virological disease.. Vet Immunol Immunopathol 2010 May 15;135(1-2):108-117.
                      doi: 10.1016/j.vetimm.2009.11.009pubmed: 20018383google scholar: lookup
                    21. Hussey SB, Clark R, Lunn KF, Breathnach C, Soboll G, Whalley JM, Lunn DP. Detection and quantification of equine herpesvirus-1 viremia and nasal shedding by real-time polymerase chain reaction.. J Vet Diagn Invest 2006 Jul;18(4):335-42.
                      doi: 10.1177/104063870601800403pubmed: 16921871google scholar: lookup
                    22. Breathnach CC, Rudersdorf R, Lunn DP. Use of recombinant modified vaccinia Ankara viral vectors for equine influenza vaccination.. Vet Immunol Immunopathol 2004 Apr;98(3-4):127-36.
                      doi: 10.1016/j.vetimm.2003.11.004pubmed: 15010222google scholar: lookup
                    23. Soboll G, Hussey SB, Whalley JM, Allen GP, Koen MT, Santucci N, Fraser DG, Macklin MD, Swain WF, Lunn DP. Antibody and cellular immune responses following DNA vaccination and EHV-1 infection of ponies.. Vet Immunol Immunopathol 2006 May 15;111(1-2):81-95.
                      doi: 10.1016/j.vetimm.2006.01.011pubmed: 16549215google scholar: lookup
                    24. Borchers K, Slater J. A nested PCR for the detection and differentiation of EHV-1 and EHV-4.. J Virol Methods 1993 Dec 31;45(3):331-6.
                      doi: 10.1016/0166-0934(93)90117-Apubmed: 8106604google scholar: lookup
                    25. Takahashi K, Coulombe PA. A transgenic mouse model with an inducible skin blistering disease phenotype.. Proc Natl Acad Sci U S A 1996 Dec 10;93(25):14776-81.
                      doi: 10.1073/pnas.93.25.14776pmc: PMC26212pubmed: 8962131google scholar: lookup
                    26. Baxi MK, Efstathiou S, Lawrence G, Whalley JM, Slater JD, Field HJ. The detection of latency-associated transcripts of equine herpesvirus 1 in ganglionic neurons.. J Gen Virol 1995 Dec;76 ( Pt 12):3113-8.
                      doi: 10.1099/0022-1317-76-12-3113pubmed: 8847517google scholar: lookup
                    27. Lunn DP, Mayhew I. Neurological examination of the horse. Equine Vet Edu 1989;44:94–101.
                    28. Slater JD. Fluorescein angiographic appearance of the normal fundus and of focal chorioretinal lesions in the horse. Invest Ophthalmol Vis Sci 1995;44:S779.
                    29. Molleda JM, Cervantes I, Galán A, Tardón R, Gallardo JM, Martín-Suárez EM. Fluorangiographic study of the ocular fundus in normal horses.. Vet Ophthalmol 2008 Sep;11 Suppl 1:2-7.
                    30. Crispin SM, Matthews AG, Parker J. The equine fundus. I: Examination, embryology, structure and function.. Equine Vet J Suppl 1990 Sep;(10):42-9.
                    31. Matthews AG, Crispin SM, Parker J. The equine fundus. II: Normal anatomical variants and colobomata.. Equine Vet J Suppl 1990 Sep;(10):50-4.
                    32. Nugent J, Birch-Machin I, Smith KC, Mumford JA, Swann Z, Newton JR, Bowden RJ, Allen GP, Davis-Poynter N. Analysis of equid herpesvirus 1 strain variation reveals a point mutation of the DNA polymerase strongly associated with neuropathogenic versus nonneuropathogenic disease outbreaks.. J Virol 2006 Apr;80(8):4047-60.
                    33. Goodman LB, Loregian A, Perkins GA, Nugent J, Buckles EL, Mercorelli B, Kydd JH, Palù G, Smith KC, Osterrieder N, Davis-Poynter N. A point mutation in a herpesvirus polymerase determines neuropathogenicity.. PLoS Pathog 2007 Nov;3(11):e160.
                    34. Lunn DP, Davis-Poynter N, Flaminio MJ, Horohov DW, Osterrieder K, Pusterla N, Townsend HG. Equine herpesvirus-1 consensus statement.. J Vet Intern Med 2009 May-Jun;23(3):450-61.

                    Citations

                    This article has been cited 12 times.
                    1. Nielsen SS, Alvarez J, Bicout DJ, Calistri P, Canali E, Drewe JA, Garin-Bastuji B, Gonzales Rojas JL, Gortázar C, Herskin M, Michel V, Miranda Chueca MÁ, Roberts HC, Padalino B, Pasquali P, Spoolder H, Ståhl K, Calvo AV, Viltrop A, Winckler C, Carvelli A, Paillot R, Broglia A, Kohnle L, Baldinelli F, Van der Stede Y. Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): infection with Equine Herpesvirus-1.. EFSA J 2022 Jan;20(1):e07036.
                      doi: 10.2903/j.efsa.2022.7036pubmed: 35035581google scholar: lookup
                    2. Laval K, Poelaert KCK, Van Cleemput J, Zhao J, Vandekerckhove AP, Gryspeerdt AC, Garré B, van der Meulen K, Baghi HB, Dubale HN, Zarak I, Van Crombrugge E, Nauwynck HJ. The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1.. Front Microbiol 2021;12:662686.
                      doi: 10.3389/fmicb.2021.662686pubmed: 33746936google scholar: lookup
                    3. Zarski LM, Weber PSD, Lee Y, Soboll Hussey G. Transcriptomic Profiling of Equine and Viral Genes in Peripheral Blood Mononuclear Cells in Horses during Equine Herpesvirus 1 Infection.. Pathogens 2021 Jan 7;10(1).
                      doi: 10.3390/pathogens10010043pubmed: 33430330google scholar: lookup
                    4. Sutton G, Thieulent C, Fortier C, Hue ES, Marcillaud-Pitel C, Pléau A, Deslis A, Guitton E, Paillot R, Pronost S. Identification of a New Equid Herpesvirus 1 DNA Polymerase (ORF30) Genotype with the Isolation of a C(2254)/H(752) Strain in French Horses Showing no Major Impact on the Strain Behaviour.. Viruses 2020 Oct 13;12(10).
                      doi: 10.3390/v12101160pubmed: 33066315google scholar: lookup
                    5. Seo MG, Ouh IO, Lee SK, Lee JS, Kwon OD, Kwak D. Molecular Detection and Genetic Characteristics of Equine Herpesvirus in Korea.. Pathogens 2020 Feb 11;9(2).
                      doi: 10.3390/pathogens9020110pubmed: 32053974google scholar: lookup
                    6. Stokol T, Soboll Hussey G. Editorial: Current Research in Equid Herpesvirus Type-1 (EHV-1).. Front Vet Sci 2019;6:492.
                      doi: 10.3389/fvets.2019.00492pubmed: 31998768google scholar: lookup
                    7. Oladunni FS, Horohov DW, Chambers TM. EHV-1: A Constant Threat to the Horse Industry.. Front Microbiol 2019;10:2668.
                      doi: 10.3389/fmicb.2019.02668pubmed: 31849857google scholar: lookup
                    8. Schnabel CL, Babasyan S, Rollins A, Freer H, Wimer CL, Perkins GA, Raza F, Osterrieder N, Wagner B. An Equine Herpesvirus Type 1 (EHV-1) Ab4 Open Reading Frame 2 Deletion Mutant Provides Immunity and Protection from EHV-1 Infection and Disease.. J Virol 2019 Nov 15;93(22).
                      doi: 10.1128/JVI.01011-19pubmed: 31462575google scholar: lookup
                    9. Holz CL, Sledge DG, Kiupel M, Nelli RK, Goehring LS, Soboll Hussey G. Histopathologic Findings Following Experimental Equine Herpesvirus 1 Infection of Horses.. Front Vet Sci 2019;6:59.
                      doi: 10.3389/fvets.2019.00059pubmed: 30886853google scholar: lookup
                    10. Pennington MR, Ledbetter EC, Van de Walle GR. New Paradigms for the Study of Ocular Alphaherpesvirus Infections: Insights into the Use of Non-Traditional Host Model Systems.. Viruses 2017 Nov 18;9(11).
                      doi: 10.3390/v9110349pubmed: 29156583google scholar: lookup
                    11. Saleh AG, Anwar SI, Abas OM, Abd-Ellatieff HA, Nasr M, Saleh I, Fukushi H, Yanai T. Effect of a single point mutation on equine herpes virus 9 (EHV-9) neuropathogenicity after intranasal inoculation in a hamster model.. J Vet Med Sci 2017 Aug 18;79(8):1426-1436.
                      doi: 10.1292/jvms.17-0076pubmed: 28717112google scholar: lookup
                    12. 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/s13567-016-0305-5pubmed: 26768993google scholar: lookup