A Review: Interactions of Equine Herpesvirus-1 with Immune System and Equine Lymphocyte

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Author(s)

Nor Dini Rusli, Khairiyah Binti Mat, Hasnita Che Harun

Affiliation(s)

Faculty of Agro Based Industry, Universiti Malaysia Kelantan, Jeli Campus, Kelantan, Malaysia.

ABSTRACT

Equine herpesvirus-1 (EHV-1) remains one of the most common viral pathogens affecting horses worldwide presenting as a persistent infection which can establish latency in nerve ganglia (trigeminal ganglion), lymphoid tissues of the respiratory tract and peripheral blood lymphocytes. EHV-1 infection induces both humoral and cellular immune responses in horses. Virus neutralising antibody, particularly in the nasopharynx, is to kill free virus shed from infected epithelial cells. Hence this antibody has important functions in reducing virus shedding and spreading infection to cohorts. Cellular immune responses, particularly those carried out by cytotoxic T lymphocyte (CTL), have been shown to be effective in killing virus-infected cells in vitro. This review underlines the state of knowledge regarding immunity to EHV-1 and also its interaction with equine lymphocyte. Finally, the review also includes the importance of the viral immediate early (IE) protein in the pathogenesis of EHV-1. This information can be used as the basis for future research.

KEYWORDS

Equine Herpesvirus-1 (EHV-1), Lymphocyte, Cytotoxic T Lymphocyte (CTL), Immune Response, Peripheral Blood Mononuclear cell (PBMC)

Cite this paper

Rusli, N. , Mat, K. and Harun, H. (2014) A Review: Interactions of Equine Herpesvirus-1 with Immune System and Equine Lymphocyte. Open Journal of Veterinary Medicine, 4, 294-307. doi: 10.4236/ojvm.2014.412036. 

 

References

[1]	Ostlund, E.N. (1993) The Equine Herpesviruses. Veterinary Clinics of North America: Equine Practice, 9, 283-294.
[2]	Mumford, J.A. (1992) Progress in the Control of Equine Influenza. In: Plowright, W., Rossdale, P.D. and Wade, J.F., Eds., Equine Infectious Diseases, VI. Proceedings of the 6th International Conference, R & W Publications, Newmarket, 207-217.
[3]	Hannant, D., Jessett, D., O’Neill, T., Dolby, C.A., Cook, R.F. and Mumford, J.A. (1993) Responses of Ponies to Equid Herpesvirus-1 ISCOM Vaccination and Challenge with Virus to the Homologous Strain. Research in Veterinary Science, 54, 299-305. http://dx.doi.org/10.1016/0034-5288(93)90126-Z
[4]	Goehring, L.S., Wagner, B., Bigbie, R., Hussey, S.B., Morley, P.S. and Lunn, D.P. (2010) Control of EHV-1 Viremia and Nasal Shedding by Commercial Vaccines. Vaccine, 28, 5203-5211. http://dx.doi.org/10.1016/j.vaccine.2010.05.065
[5]	Allen, G.P., Yeargan, M., Costa, L.R.R. and Cross, R. (1995) Major Histocompatibility Complex Class I-Restricted Cytotoxic T-Lymphocyte Responses in Horses Infected with Equine Herpesvirus-1. Journal of Virology, 69, 606-612.
[6]	Allen, G.P., Kydd, J.H., Slater, J.D. and Smith, K.C. (2004) Equid Herpesvirus-1 (EHV-1) and -4 (EHV-4) Infections. In: Coetzer, J.A.W. and Tustin, R.C., Eds., Infectious Diseases of Livestock, 2nd Edition, Oxford Press, Cape Town, 829-859.
[7]	Kydd, J.H., Wattrang, E. and Hannant, D. (2003) Pre-Infection Frequencies of Equine Herpesvirus-1 Specific, Cytotoxic T Lymphocytes Correlate with Protection against Abortion Following Experimental Infection of Pregnant Mares. Veterinary Immunology and Immunopathology, 96, 207-217. http://dx.doi.org/10.1016/j.vetimm.2003.08.004
[8]	Allen, G.P. (2008) Risk Factors for Development of Neurologic Disease after Experimental Exposure to Equine Herpesvirus-1 in Horses. American Journal of Veterinary Research, 69, 1595-1600. http://dx.doi.org/10.2460/ajvr.69.12.1595
[9]	Kydd, J.H., Townsend, H.G.G. and Hannant, D. (2006) The Equine Immune Response to Equine Herpesvirus-1: The Virus and Its Vaccines. Veterinary Immunology and Immunopathology, 111, 15-30.http://dx.doi.org/10.1016/j.vetimm.2006.01.005
[10]	Soboll, G., Whalley, J.M., Koen, M.T., Allen, G.P., Fraser, D.G., Macklin, M.D., Swain, W.F. and Lunn, D.P. (2003) Identification of Equine Herpesvirus-1 Antigens Recognized by Cytotoxic T Lymphocytes. Journal of General Virology, 84, 2625-2634. http://dx.doi.org/10.1099/vir.0.19268-0
[11]	Allen, G.P., Bolin, D.C., Bryant, U., Carter, C.N., Giles, R.C., Harrison, L.R., Hong, C.B., Jackson, C.B., Poonacha, K., Wharton, R. and Williams, N.M. (2008) Prevalence of Latent, Neuropathogenic Equine Herpesvirus-1 in the Thoroughbred Broodmare Population of Central Kentucky. Equine Veterinary Journal, 40, 105-110.
[12]	Kydd, J.H., Smith, K.C., Hannant, D., Livesay, G.J. and Mumford, J.A. (1994) Distribution of Equid Herpesvirus-1 (EHV-1) in the Respiratory Tract of Ponies: Implication for Vaccination Strategies. Equine Veterinary Journal, 26, 466-469. http://dx.doi.org/10.1111/j.2042-3306.1994.tb04051.x
[13]	Patel, J.R., Edington, N. and Mumford, J.A. (1982) Variation in Cellular Tropism between Isolates of Equine Herpesvirus-1 in Foals. Archives of Virology, 74, 41-51. http://dx.doi.org/10.1007/BF01320781
[14]	Kydd, J.H., Smith, K.C., Hannant, D., Livesay, G.J. and Mumford, J.A. (1994) Distribution of Equid Herpesvirus-1 (EHV-1) in the Respiratory Tract-Associated Lymphoid Tissue: Implications for Cellular Immunity. Equine Veterinary Journal, 26, 470-473. http://dx.doi.org/10.1111/j.2042-3306.1994.tb04052.x
[15]	Allen, G.P. and Bryans, J.T. (1986) Molecular, Epizootiology, Pathogenesis and Prophylaxis of Equine Herpes Virus-1 Infections. Progress in Veterinary Microbiology and Immunology, 2, 78-144.
[16]	Edington, N., Smyth, B. and Griffiths, L. (1991) The Role of Endothelial Cell Infection in the Endometrium, Placenta and Foetus of Equid Herpesvirus 1 (EHV-1) Abortions. Journal of Comparative Pathology, 104, 379-387. http://dx.doi.org/10.1016/S0021-9975(08)80148-X
[17]	Smith, K.C., Whitwell, K.E., Binns, M.M., Dolby, C.A., Hannant, D. and Mumford, J.A. (1992) Abortion of Virologically Negative Foetuses Following Experimental Challenge of Pregnant Pony Mares with Equid Herpesvirus 1. Equine Veterinary Journal, 24, 256-259. http://dx.doi.org/10.1111/j.2042-3306.1992.tb02830.x
[18]	Smith, K.C. and Borchers, K. (2001) A Study of the Pathogenesis of Equid Herpesvirus-1 (EHV-1) Abortion by DNA In-Situ Hybridization. Journal of Comparative Pathology, 125, 304-310. http://dx.doi.org/10.1053/jcpa.2001.0513
[19]	Smith, K.L., Allen, G.P., Branscum, A.J., Frank Cook, R., Vickers, M.L., Timoney, P.J. and Balasuriya, U.B. (2010) The Increased Prevalence of Neuropathogenic Strains of EHV-1 in Equine Abortions. Veterinary Microbiology, 141, 5-11. http://dx.doi.org/10.1016/j.vetmic.2009.07.030
[20]	Smith, K.C., Whitwell, K.E., Blunden, A.S., Bestbier, M.E., Scase, T.J., Geraghty, R.J., Nugent, J., Davis-Poynter, N.J. and Cardwell, J.M. (2004) Equine Herpesvirus-1 Abortion: Atypical Cases with Lesions Largely or Wholly Restricted to the Placenta. Equine Veterinary Journal, 36, 79-82. http://dx.doi.org/10.2746/0425164044864732
[21]	Smith, K.C., Mumford, J.A. and Lakhani, K. (1996) A Comparison of Equid Herpesvirus-1 (EHV-1) Vascular Lesions in the Early versus Late Pregnant Equine Uterus. Journal of Comparative Pathology, 114, 231-247. http://dx.doi.org/10.1016/S0021-9975(96)80045-4
[22]	Jackson, J.C., Golden, G.T. and Benjamin, R.M. (1977) The Distribution of Olfactory Input in the Opossum Mediodorsal Nucleus. Brain Research, 138, 229-240. http://dx.doi.org/10.1016/0006-8993(77)90742-9
[23]	Platt, H., Singh, H. and Whitwellm, K.E. (1980) Pathological Observations on an Outbreak of Paralysis in Broodmares. Equine Veterinary Journal, 12, 118-126. http://dx.doi.org/10.1111/j.2042-3306.1980.tb03398.x
[24]	Edington, N., Bridges, C.G. and Patel, J.R. (1986) Endothelial Cell Infection and Thrombosis in Paralysis Caused by Equid Herpesvirus-1: Equine Stroke. Archives of Virology, 90, 111-124. http://dx.doi.org/10.1007/BF01314149
[25]	Roizman, B., Desrosiers, R.S., Fleckenstein, B., Lopez, C., Minson, A.C. and Studdert, M.J. (1992) The Family Herpesviridae: An Update. Archives of Virology, 123, 425-449. http://dx.doi.org/10.1007/BF01317276
[26]	Edington, N., Welch, H.M. and Griffiths, L. (1994) The Prevalence of Latent Equid Herpesviruses in the Tissues of 40 Abattoir Horses. Equine Veterinary Journal, 26, 140-142. http://dx.doi.org/10.1111/j.2042-3306.1994.tb04353.x
[27]	Slater, J.C., Borchers, K., Thackray, A.M. and Field, H. (1994) The Trigeminal Ganglion Is a Site of Equine Herpsvirus-1 (EHV-1) Latency and Reactivation in the Horse. Journal of General Virology, 75, 2007-2016. http://dx.doi.org/10.1099/0022-1317-75-8-2007
[28]	Welch, H.M., Bridges, C.G., Lyon, A.M., Griffiths, L. and Edington, N. (1992) Latent Equid Herpesviruses 1 and 4: Detection and Distinction Using the Polymerase Chain Reaction and Co-Cultivation from Lymphoid Tissues. Journal of General Virology, 73, 261-268. http://dx.doi.org/10.1099/0022-1317-73-2-261
[29]	Chester, P.M., Allsop, R., Purewal, A. and Edington, N. (1997) Detection of Latency-Associated Transcripts of Equid Herpesvirus 1 in Equine Leukocytes but Not in Trigeminal Ganglia. Journal of Virology, 71, 3437-3443.
[30]	Smith, P.M., Zhang, Y., Jennings, S.R. and O’Callaghan, D.J. (1998) Characterization of the Cytolytic T-Lymphocyte Response to a Candidate Vaccine Strain of Equine Herpesvirus 1 in CBA Mice. Journal of Virology, 72, 5366-5372.
[31]	Chesters, P.M., Hughes, A. and Edington, N. (2000) Equid Herpesvirus 1: Platelets and Alveolar Macrophages Are Potential Sources of Activated TGF-B1 in the Horse. Veterinary Immunology and Immunopathology, 75, 71-79. http://dx.doi.org/10.1016/S0165-2427(00)00187-2
[32]	Doll, E.R., Wallace, M.E., Bryans, J.T. and Richards, M.G. (1953) Complement-Fixation Antibody Response Following Administration of Equine Virus Abortion Vaccine. American Journal of Veterinary Research, 14, 46-48.
[33]	Thomson, G.R., Mumford, J.A., Campbell, J., Griffiths, L. and Clapham, P. (1976) Serological Detection of Equid Herpesvirus 1 Infections of the Respiratory Tract. Equine Veterinary Journal, 8, 58-65. http://dx.doi.org/10.1111/j.2042-3306.1976.tb03291.x
[34]	Allen, G., Coogle, L.D., Ostlund, E.N. and Yeargan, M.R. (1992) Molecular Dissection of Two Major Equine Herpesvirus-1 Glycoprotein Antigens (Gb and Gc) that Elicit Humoral Immune Responses in the Horse. In: Plowright, W., Rossdale, P.D. and Wade, J.F., Eds., Equine Infectious Diseases VI, R&W Publications, Newmarket, 181-193.
[35]	Fitzpatrick, D.R. and Studdert, M.J. (1984) Immunologic Relationships between Equine Herpesvirus Type 1 (Equine Abortion Virus) and Type 4 (Equine Rhinopneumonitis Virus). American Journal of Veterinary Research, 45, 1947-1952.
[36]	Crabb, B.S. and Studdert, M.J. (1993) Epitopes of Glycoprotein G of Equine Herpesviruses 4 and 1 Located Near the C Termini Elicit Type Specific Antibody Responses in the Natural Host. Journal of Virology, 67, 6332-6338.
[37]	Soboll Hussey, G., Hussey, S.B., Wagner, B., Horohov, D.W., Van De Walle, G.R., Osterrieder, N., Goehring, L.S., Rao, S. and Lunn, D.P. (2011) Evaluation of Immune Responses Following Infection of Ponies with an EHV-1 ORF1/2 Deletion Mutant. Veterinary Research, 42, 23. http://dx.doi.org/10.1186/1297-9716-42-23
[38]	Crabb, B.S., Macpherson, C.M., Reubel, G.H., Browning, G.F., Studdert, M.J. and Drummer, H.E. (1995) A Type- Specific Serological Test to Distinguish Antibodies to Equine Herpesviruses 4 and 1. Archives of Virology, 140, 245- 258. http://dx.doi.org/10.1007/BF01309860
[39]	Soboll, G., Hussey, S.B., Whalley, J.M., Allen, G.P., Koen, M.T., Santucci, N., Fraser, D.G., Macklin, M.D., Swain, W.F. and Lunn, D.P. (2006) Antibody and Cellular Immune Responses Following DNA Vaccination and EHV-1 Infection of Ponies. Veterinary Immunology and Immunopathology, 111, 81-95. http://dx.doi.org/10.1016/j.vetimm.2006.01.011
[40]	Mumford, E.L., Traub-Dargatz, J.L., Carman, J., Callan, R.J., Collins, J.K., Goltz, K.L., Romm, S.R., Tarr, S.F. and Salman, M.D. (2003) Occurrence of Infectious Upper Respiratory Tract Disease and Response to Vaccination in Horses on Six Sentinel Premises in Northern Colorado. Equine Veterinary Journal, 35, 72-77. http://dx.doi.org/10.2746/042516403775467379
[41]	Sheoran, A.S., Lunn, D.P. and Holmes, M.A. (1998) Monoclonal Antibodies to Subclass-Specific Antigenic Determinants on Equine Immunoglobulin Gamma Chains and Their Characterization. Veterinary Immunology and Immunopathology, 62, 153-165. http://dx.doi.org/10.1016/S0165-2427(97)00162-1
[42]	Lunn, D.P., Holmes, M.A., Schram, B. and Duffus, W.P. (1995) Monoclonal Antibodies Specific for Equine IgG Sub-Isotypes Including an Antibody Which Recognizes B Lymphocytes. Veterinary Immunology and Immunopathology, 47, 239-251. http://dx.doi.org/10.1016/0165-2427(95)97067-J
[43]	Wagner, B., Miller, D.C., Lear, T.L. and Antczak, D.F. (2004) The Complete Map of the Ig Heavy Chain Constant Gene Region Reveals Evidence for Seven IgG Isotypes and for IgD in the Horse. Journal of Immunology, 173, 3230-3242. http://dx.doi.org/10.4049/jimmunol.173.5.3230
[44]	Breathnach, C.C., Yeargan, M.R., Sheoran, A.S. and Allen, G.P. (2001) The Mucosal Humoral Immune Response of the Horse to Infective Challenge and Vaccination with Equine Herpesvirus-1 Antigens. Equine Veterinary Journal, 33, 651-657. http://dx.doi.org/10.2746/042516401776249318
[45]	Ruitenberg, K.M., Love, D.N., Gilkerson, J.R., Wellington, J.E. and Whalley, J.M. (2000) Equine Herpesvirus 1 (EHV-1) Glycoprotein D DNA Inoculation in Horses with Pre-Existing EHV-1/EHV-4 Antibody. Veterinary Microbiology, 76, 117-127. http://dx.doi.org/10.1016/S0378-1135(00)00237-6
[46]	Sheoran, A.S., Sponseller, B.T., Holmes, M.A. and Timoney, J.F. (1997) Serum and Mucosal Antibody Isotype Responses to M-Like Protein (Sem) of Streptococcus equi in Convalescent and Vaccinated Horses. Veterinary Immunology and Immunopathology, 59, 239-251. http://dx.doi.org/10.1016/S0165-2427(97)00074-3
[47]	Nelson, K.M., Schram, B.R., Mcgregor, M.W., Sheoran, A.S., Olsen, C.W. and Lunn, D.P. (1998) Local and Systemic Isotype-Specific Antibody Responses to Equine Influenza Virus Infection versus Conventional Vaccination. Vaccine, 16, 1306-1313. http://dx.doi.org/10.1016/S0264-410X(98)00009-7
[48]	Hannant, D., Easeman, R. and Mumford, J.A. (1999) Equine Mucosal Immune System: Intranasal Vaccination with Inactivated Equine Influenza Virus Protects from Infection. In: Wernery, O., Wade, J.F., Mumford, J.A. and Kaaden, O.R., Eds., Proceedings of the 8th International Conference on Equine Infectious Diseases, R&W Publications Ltd., Newmarket, 50-56.
[49]	Goodman, L.B., Wagner, B., Flaminio, M.J., Sussman, K.H., Metzger, S.M., Holland, R. and Osterrieder, N. (2006) Comparison of the Efficacy of Inactivated Combination and Modified-Live Virus Vaccines against Challenge Infection with Neuropathogenic Equine Herpesvirus Type 1 (EHV-1). Vaccine, 24, 3636-3645. http://dx.doi.org/10.1016/j.vaccine.2006.01.062
[50]	Paillot, R., Daly, J.M., Luce, R., Montesso, F., Davis-Poynter, N., Hannant, D. and Kydd, J.H. (2007) Frequency and Phenotype of EHV-1 Specific, IFN-Gamma Synthesizing Lymphocytes in Ponies: The Effects of Age, Pregnancy and Infection. Developmental and Comparative Immunology, 31, 202-214. http://dx.doi.org/10.1016/j.dci.2006.05.010
[51]	Paillot, R., Daly, J.M., Juillard, V., Minke, J.M., Hannant, D. and Kydd, J.H. (2005) Equine Interferon Gamma Synthesis in Lymphocytes after in Vivo Infection and in Vitro Stimulation with EHV-1. Vaccine, 23, 4541-4551. http://dx.doi.org/10.1016/j.vaccine.2005.03.048
[52]	Coombs, D.K., Patton, T., Kohler, A.K., Soboll, G., Breathnach, C., Townsend, H.G. and Lunn, D.P. (2006) Cytokine Responses to EHV-1 Infection in Immune and Non-Immune Ponies. Veterinary Immunology and Immunopathology, 111, 109-116. http://dx.doi.org/10.1016/j.vetimm.2006.01.013
[53]	Wagner, B., Hillegas, J.M. and Antczak, D.F. (2006) A Monoclonal Antibody to Equine Interleukin 4. Veterinary Immunology and Immunopathology, 110, 363-367. http://dx.doi.org/10.1016/j.vetimm.2006.01.001
[54]	Edington, N., Bridges, C.G. and Griffiths, L. (1989) Equine Interferons Following Exposure to Equid Herpesvirus-1 or -4. Journal of Interferon Research, 9, 389-392. http://dx.doi.org/10.1089/jir.1989.9.389
[55]	Durbin, J.E., Fernandez-Sesma, A., Lee, C.K., Rao, T.D., Frey, A.B., Moran, T.M., Vukmanovic, S., García-Sastre, A. and Levy, D.E. (2000) Type I IFN Modulates Innate and Specific Antiviral Immunity. Journal of Immunology, 164, 4220-4228. http://dx.doi.org/10.4049/jimmunol.164.8.4220
[56]	Ito, T., Wang, Y.H. and Liu, Y.J. (2005) Plasmacytoid Dendritic Cell Precursors/Type I Interferon-Producing Cells Sense Viral Infection by Toll-Like Receptor (TLR) 7 and TLR9. Springer Seminars in Immunopathology, 26, 221-229. http://dx.doi.org/10.1007/s00281-004-0180-4
[57]	Jung, A., Kato, H., Kumagai, Y., Kumar, H., Kawai, T., Takeuchi, O. and Akira, S. (2008) Lymphocytoid Choriomeningitis Virus Activates Plasmacytoid Dendritic Cells and Induces a Cytotoxic T-Cell Response via MyD88. Journal of Virology, 82, 196-206. http://dx.doi.org/10.1128/JVI.01640-07
[58]	Szabo, G. and Dolganiuc, A. (2008) The Role of Plasmacytoid Dendritic Cell Derived IFNα in Antiviral Immunity. Critical Reviews in Immunology, 28, 61-94. http://dx.doi.org/10.1615/CritRevImmunol.v28.i1.40
[59]	Pedersen, L.G., Castelruiz, Y., Jacobsen, S. and Aasted, B. (2002) Identification of Monoclonal Antibodies that Cross-React with Cytokines from Different Animal Species. Veterinary Immunology and Immunopathology, 88, 111-122. http://dx.doi.org/10.1016/S0165-2427(02)00139-3
[60]	Breathnach, C.C., Soboll, G., Suresh, M. and Lunn, D.P. (2005) Equine Herpesvirus-1 Infection Induces IFN-γ Production by Equine T Lymphocyte Subsets. Veterinary Immunology and Immunop-athology, 103, 207-215. http://dx.doi.org/10.1016/j.vetimm.2004.09.024
[61]	Paillot, R., Ellis, S.A., Daly, J.M., Audonnet, J.C., Minke, J.M., Davis-Poynter, N., Hannant, D. and Kydd, J.H. (2006) Characterisation of CTL and IFN-γ Synthesis in Ponies Following Vaccination with a NYVAC-Based Construct Coding for EHV-1 Immediate Early Gene, Followed by Challenge Infection. Vaccine, 24, 1490-1500. http://dx.doi.org/10.1016/j.vaccine.2005.10.019
[62]	Luce, R., Shepherd, M., Paillot, R., Blacklawst, B., Wood, J.L. and Kydd, J.H. (2007) Equine Herpesvirus-1-Specific Intereferon Gamma (IFNγ) Synthesis by Peripheral Blood Mononuclear Cells in Thoroughbred Horses. Equine Veterinary Journal, 39, 202-209. http://dx.doi.org/10.2746/042516407X174216
[63]	Wagner, B., Hillegas, J.M., Brinker, D.R., Horohov, D.W. and Antczak, D.F. (2008) Characterization of Monoclonal Antibodies to Equine Interleukin-10 and Detection of T Regulatory 1 Cells in Horses. Veterinary Immunology and Immunopathology, 122, 57-64. http://dx.doi.org/10.1016/j.vetimm.2007.10.012
[64]	Wagner, B., Hillegas, J.M., Flaminio, M.J.B.F. and Wattrang, E. (2008) Monoclonal Antibodies to Equine Interferon-α (IFN-α): New Tools to Neutralize IFN Activity and to Detect Secreted IFN-α. Veterinary Immunology and Immunopathology, 125, 315-325. http://dx.doi.org/10.1016/j.vetimm.2008.05.016
[65]	Wagner, B. and Freer, H. (2009) Development of a Bead-Based Multiplex Assay for Simultaneous Quantification of Cytokines in Horses. Veterinary Immunology and Immunopathology, 127, 242-248. http://dx.doi.org/10.1016/j.vetimm.2008.10.313
[66]	Soboll, G., Horohov, D.W., Aldridge, B.M., Olsen, C.W., Mcgregor, M.W., Drape, R.J., Macklin, M.D., Swain, W.F. and Lunn, D.P. (2003) Regional Antibody and Cellular Immune Responses to Equine Influenza Virus Infection, and Particle Mediated DNA Vaccination. Veterinary Immunology and Immunopathology, 94, 47-62. http://dx.doi.org/10.1016/S0165-2427(03)00060-6
[67]	Breathnach, C.C., Rudersdorf, R. and Lunn, D.P. (2004) Use of Recombinant Modified Vaccinia Ankara Viral Vectors for Equine Influenza Vaccination. Veterinary Immunology and Immunopathology, 98, 127-136. http://dx.doi.org/10.1016/j.vetimm.2003.11.004
[68]	Breathnach, C.C., Clark, H.J., Clark, R.C., Olsen, C.W., Townsend, H.G. and Lunn, D.P. (2006) Immunization with Recombinant Modified Vaccinia Ankara (rMVA) Constructs Encoding the HA or NP Gene Protects Ponies from Equine Influenza Virus Challenge. Vaccine, 24, 1180-1190. http://dx.doi.org/10.1016/j.vaccine.2005.08.091
[69]	Fraser, D.G., Oaks, J.L., Brown, W.C. and Mcguire, T.C. (2002) Identification of Broadly Recognized, T Helper 1 Lymphocyte Epitopes in an Equine Lentivirus. Immunology, 105, 295-305. http://dx.doi.org/10.1046/j.0019-2805.2001.01370.x
[70]	Fraser, D.G., Mealey, R.H. and Mcguire, T.C. (2003) Selecting Peptides to Optimize Th1 Responses to an Equine Lentivirus Using HLA-DR Binding Motifs and Defined HIV-1 Th Peptides. Immunogenetics, 55, 508-514. http://dx.doi.org/10.1007/s00251-003-0600-y
[71]	Lopez, A.M., Hines, M.T., Palmer, G.H., Alperin, D.C. and Hines, S.A. (2002) Identification of Pulmonary T-Lym- phocyte and Serum Antibody Isotype Responses Associated with Protection against Rhodococcus equi. Clinical and Diagnostic Laboratory Immunology, 9, 1270-1276.
[72]	Pusterla, N., Wilson, W.D., Conrad, P.A., Barr, B.C., Ferraro, G.L., Daft, B.M. and Leutenegger, C.M. (2006) Cytokine Gene Signatures in Neural Tissue of Horses with Equine Protozoal Myeloencephalitis or Equine Herpes Type 1 Myeloencephalopathy. Veterinary Record, 159, 341-345. http://dx.doi.org/10.1136/vr.159.11.341
[73]	Wagner, B., Burton, A. and Ainsworth, D.M. (2010) Interferon-Gamma, Interleukin-4 and Interleukin-10 Production by T Helper Cells Reveals Intact Th1 and Regulatory TR1 Cell Activation and a Delay of the Th2 Cell Response in Equine Neonates and Foals. Veterinary Research, 41, 47. http://dx.doi.org/10.1051/vetres/2010019
[74]	Soboll, G., Breathnach, C.C., Kydd, J.H., Hussey, S.B., Mealey, R.M. and Lunn, D.P. (2010) Vaccination of Ponies with the IE Gene of EHV-1 in a Recombinant Modified Live Vaccinia Vector Protects against Clinical and Virological Disease. Veterinary Immunology and Immunopathology, 135, 108-117. http://dx.doi.org/10.1016/j.vetimm.2009.11.009
[75]	Dutta, S.K., Myrup, A. and Bumgardner, M.K. (1980) Lymphocyte Responses to Virus and Mitogen in Ponies during Experimental Infection with Equine Herpesvirus 1. American Journal of Veterinary Research, 41, 2066-2068.
[76]	Hannant, D., O’Neill, T., Jessett, D.M. and Mumford, J.A. (1991) Evidence for Non-Specific Immunosuppression during the Development of Immune Responses to Equid Herpesvirus-1. Equine Veterinary Journal, 23, 41-45.
[77]	Chong, Y.C. and Duffus, W.P. (1992) Immune Responses of Specific Pathogen Free Foals to EHV-1 Infection. Veterinary Microbiology, 32, 215-239. http://dx.doi.org/10.1016/0378-1135(92)90146-K
[78]	Bumgardner, M.K., Dutta, S.K., Campbell, D.L. and Myrup, A.C. (1982) Lymphocytes from Ponies Experimentally Infected with Equine Herpesvirus 1: Subpopulation Dynamics and Their Response to Mitogens. American Journal of Veterinary Research, 43, 1308-1310.
[79]	Charan, S., Palmer, K., Chester, P., Mire-Sluis, A.R., Meager, A. and Edington, N. (1997) Transforming Growth Factor-β Induced by Live or Ultraviolet-Inactivated Equid Herpes Virus Type-1 Mediates Immunosuppression in the Horse. Immunology, 90, 586-591. http://dx.doi.org/10.1046/j.1365-2567.1997.00202.x
[80]	Van Der Meulen, K.M., Favoreel, H.W., Pensaert, M.B. and Nauwynck, H.J. (2006) Immune Escape of Equine Herpesvirus 1 and Other Herpesviruses of Veterinary Importance. Veterinary Immunology and Immunopathology, 111, 31- 40. http://dx.doi.org/10.1016/j.vetimm.2006.01.006
[81]	Kydd, J.H., Hannant, D. and Mumford, J.A. (1996) Residence and Recruitment of Leucocytes to the Equine Lung after EHV-1 Infection. Veterinary Immunology and Immunopathology, 52, 15-26. http://dx.doi.org/10.1016/0165-2427(95)05533-9
[82]	Lunn, D.P., Holmes, M.A. and Duffus, W.P. (1991) Three Monoclonal Antibodies Identifying Antigens on All Equine T Lymphocytes, and Two Mutually Exclusive T-Lymphocyte Subsets. Immunology, 74, 251-257.
[83]	Allen, G.P., Kydd, J.H., Slater, J.D. and Smith, K.C. (1999) Advances in Understanding of the Pathogenesis, Epidemiology, and Immunological Control of Equid Herpesvirus Abortion. In: Wernery, U., Wade, J.F., Mumford, J.A. and Kaaden, O.R., Eds., Equine Infectious Diseases VIII. Proceedings of the 8th International Conference, R & W Publications, Newmarket, 129-146.
[84]	O’Neill, T., Kydd, J.H., Allen, G.P., Wattrang, E., Mumford, J.A. and Hannant, D. (1999) Determination of Equid Herpesvirus 1-Specific, CD8+, Cytotoxic T Lymphocyte Precursor Frequencies in Ponies. Veterinary Immunology and Immunopathology, 70, 43-54. http://dx.doi.org/10.1016/S0165-2427(99)00037-9
[85]	Siedek, E.M., Whelan, M., Edington, N. and Hamblin, A. (1999) Equine Herpesvirus Type 1 Infects Dendritic Cells in Vitro: Stimulation of T Lymphocyte Proliferation and Cytotoxicity by Infected Dendritic Cells. Veterinary Immunology and Immunopathology, 67, 17-32. http://dx.doi.org/10.1016/S0165-2427(98)00203-7
[86]	Hannant, D., O’Neill, T., Ostlund, E.N., Kydd, J.H., Hopkin, P.J. and Mumford, J.A. (1999) Equid Herpesvirus-In- duced Immunosuppression Is Associated with Lymphoid Cells and Not Soluble Circulating Factors. Viral Immunology, 12, 313-321. http://dx.doi.org/10.1089/vim.1999.12.313
[87]	O’Neill, T. (1995) T Lymphocyte Responses to Equid Herpesviruses-1 and -4 in Horses. Ph.D. Thesis, Open University, London.
[88]	Scott, J.C., Dutta, S.K. and Myrup, A.C. (1983) In Vivo Harboring of Equine Herpesvirus-1 in Leukocyte Populations and Subpopulations and Their Quantitation from Experimentally Infected Ponies. American Journal of Veterinary Research, 44, 1344-1348.
[89]	Dutta, S.K. and Myrup, A.C. (1983) Infectious Center Assay of Intracellular Virus and Infective Virus Titer for Equine Mononuclear Cells Infected in Vivo and in Vitro with Equine Herpesviruses. Canadian Journal of Comparative Medicine, 47, 64-69.
[90]	Van Der Meulen, K.M., Nauwynck, H.J., Buddaert, W. and Pensaert, M.B. (2000) Replication of Equine Herpesvirus Type 1 in Freshly Isolated Equine Peripheral Blood Mononuclear Cells and Changes in Susceptibility Following Mitogen Stimulation. Journal of General Virology, 81, 21-25.
[91]	Gryspeerdt, A.C., Vandekerckhove, A.P., Garre, B., Barbe, F., Van De Walle, G.R. and Nauwynck, H.J. (2010) Differences in Replication Kinetics and Cell Tropism between Neurovirulent and Non-Neurovirulent EHV1 Strains during the Acute Phase of Infection in Horses. Veterinary Microbiology, 142, 242-253. http://dx.doi.org/10.1016/j.vetmic.2009.10.015
[92]	Goodman, L.B., Loregian, A., Perkins, G.A., Nugent, J., Buckles, E.L., Mercorelli, B., Kydd, J.H., Palù, G., Smith, K.C., Osterrieder, N. and Davis-Poynter, N. (2007) A Point Mutation in a Herpesvirus Polymerase Determines Neuropathogenicity. PLoS Pathogens, 3, e160. http://dx.doi.org/10.1371/journal.ppat.0030160
[93]	Wilsterman, S., Soboll-Hussey, G., Lunn, D.P., Ashton, L.V., Callan, R.J., Hussey, S.B., Rao, S. and Goehring, L.S. (2011) Equine Herpesvirus-1 Infected Peripheral Blood Mononuclear Cell Subpopulations during Viremia. Veterinary Microbiology, 149, 40-47. http://dx.doi.org/10.1016/j.vetmic.2010.10.004
[94]	Ambagala, A.P.N., Gopinath, R.S. and Srikumaran, S. (2004) Peptide Transport Activity of the Transporter Associated with Antigen Processing (TAP) Is Inhibited by an Early Protein of Equine Herpesvirus-1. Journal of General Virology, 85, 349-353. http://dx.doi.org/10.1099/vir.0.19563-0
[95]	Favoreel, H.W., Van Minnebruggen, G., Van De Walle, G.R., Ficinska, J. and Nauwynck, H.J. (2006) Herpesvirus Interference with Virus-Specific Antibodies: Bridging Antibodies, Internalizing Antibodies, and Hiding from Antibodies. Veterinary Microbiology, 113, 257-263. http://dx.doi.org/10.1016/j.vetmic.2005.11.003
[96]	Van De Walle, G.R., May, M.L., Sukhumavasi, W., Von Einem, J. and Osterrieder, N. (2007) Herpesvirus Chemokine- Binding Glycoprotein G (gG) Efficiently Inhibits Neutrophil Chemotaxis in Vitro and in Vivo. Journal of Immunology, 179, 4161-4169. http://dx.doi.org/10.4049/jimmunol.179.6.4161
[97]	Van De Walle, G.R., Goupil, R., Wishon, C., Damiani, A., Perkins, G.A. and Osterrieder, N. (2009) A Single-Nucleo- tide Polymorphism in a Herpesvirus DNA Polymerase Is Sufficient to Cause Lethal Neurological Disease. Journal of Infectious Diseases, 200, 20-25.
[98]	Van De Walle, G.R., Jarosinski, K.W. and Osterrieder, N. (2008) Alphaherpesviruses and Chemokines: Pas De Deux Not Yet Brought to Perfection. Journal of Virology, 82, 6090-6097. http://dx.doi.org/10.1128/JVI.00098-08
[99]	Stokes, A. and Wardley, R.C. (1988) ADCC and Complement-Dependent Lysis as Immune Mechanisms against EHV-1 Infection in the Horse. Research in Veterinary Science, 44, 295-302.
[100]	Huemer, H.P., Nowotny, N., Crabb, B.S., Meyer, H. and Hübert, P.H. (1995) gp13 (EHV-gC): A Complement Receptor Induced by Equine Herpesviruses. Virus Research, 37, 113-126. http://dx.doi.org/10.1016/0168-1702(95)00027-N
[101]	Rappocciolo, G., Birch, J. and Ellis, S.A. (2003) Down-Regulation of MHC Class I Expression by Equine Herpesvirus-1. Journal of General Virology, 84, 293-300. http://dx.doi.org/10.1099/vir.0.18612-0
[102]	Nugent, J., Birch-Machin, I., Smith, K.C., Mumford, J.A., Swann, Z., Newton, J.R., Bowden, R.J., Allen, G.P. and Davis-Poynter, N. (2006) Analysis of Equid Herpesvirus 1 Strain Variation Reveals a Point Mutation of the DNA Polymerase Strongly Associated with Neuropathogenic versus Nonneuropathogenic Disease Outbreaks. Journal of Virology, 80, 4047-4060. http://dx.doi.org/10.1128/JVI.80.8.4047-4060.2006
[103]	Van Der Meulen, K.M., Nauwynck, H.J. and Pensaert, M.B. (2003) Absence of Viral Antigens on the Surface of Equine Herpesvirus-1-Infected Peripheral Blood Mononuclear Cells: A Strategy to Avoid Complement-Mediated Lysis. Journal of General Virology, 84, 93-97. http://dx.doi.org/10.1099/vir.0.18864-0
[104]	Crabb, B.S. and Studdert, M.J. (1996) Equine Rhinopneumonitis (Equine Herpesvirus 4) and Equine Abortion (Equine Herpesvirus 1). In: Studdert, M.J., Ed., Virus Infections of Equines, Elsevier Sciences, 11-37.
[105]	Slater, J. and Hannant, D. (2000) Equine Immunity to Viruses. Veterinary Clinics of North America, 16, 49-68.
[106]	Mumford, J.A., Rossdale, P.D., Jessett, D.M., Gann, S.J., Ousey, J. and Cook, R.F. (1987) Serological and Virological Investigations of an Equid Herpesvirus 1 (EHV-1) Abortion Storm on a Stud Farm in 1985. Journal of Reproduction and Fertility Supplement, 35, 509-518.
[107]	Rosas, C.T., Goodman, L.B., Von Einem, J. and Osterrieder, N. (2006) Equine Herpesvirus Type 1 Modified Live Virus Vaccines: Quo vaditis? Expert Review of Vaccines, 5, 119-131. http://dx.doi.org/10.1586/14760584.5.1.119                   eww141215lx