Risk factors for development of neurologic disease after experimental exposure to equine herpesvirus-1 in horses.

OBJECTIVE To identify risk factors associated with development of clinical neurologic signs in horses exposed to equine herpesvirus-1 (EHV-1). ANIMALS 36 adult horses. PROCEDURES Blood samples collected before and after challenge inoculation with nonneuropathogenic or neuropathogenic EHV-1 were analyzed for leukocyte-associated viremia, serum neutralizing antibody, and EHV-1-specific cytotoxic T-lymphocyte precursors (CTLPs). Associations between variables and neurologic disease and correlations between age category or breed and development of neurologic disease were examined. RESULTS 9 horses developed CNS signs (ataxia, hind limb paresis or paralysis, bladder atony, or recumbency). Neurologic deficits were correlated with infection by a neuropathogenic strain of EHV-1, age>20 years, high postexposure viremic load, and low preexposure concentration of CTLPs. No significant correlations were observed between preinfection titers or horse breed and postinfection development of neurologic signs. CONCLUSIONS AND CLINICAL RELEVANCE Horses with high concentrations of preexisting CTLPs, regardless of age, strain of virus, or titer, were more likely to control the magnitude of postinfection leukocyte-associated viremia and subsequent development of neurologic disease; therefore, CTLPs appear to be a critical requirement for protective immunity against EHV-1-induced myeloencephalopathy. The importance of achieving immunity related to high concentrations of vaccine-induced CTLPs in horses at high risk for exposure to neuropathogenic strains of EHV-1 is indicated.

[1]  G. Allen,et al.  Outbreak of neurologic disease caused by equine herpesvirus-1 at a university equestrian center. , 2007, Journal of veterinary internal medicine.

[2]  G. Allen,et al.  Quantification by real-time PCR of the magnitude and duration of leucocyte-associated viraemia in horses infected with neuropathogenic vs. non-neuropathogenic strains of EHV-1. , 2010, Equine veterinary journal.

[3]  R. Bowden,et al.  Analysis of Equid Herpesvirus 1 Strain Variation Reveals a Point Mutation of the DNA Polymerase Strongly Associated with Neuropathogenic versus Nonneuropathogenic Disease Outbreaks , 2006, Journal of Virology.

[4]  R. Toribio,et al.  Equine herpesvirus 1 and 4. , 2004, The Veterinary clinics of North America. Equine practice.

[5]  J. Kydd,et al.  Pre-infection frequencies of equine herpesvirus-1 specific, cytotoxic T lymphocytes correlate with protection against abortion following experimental infection of pregnant mares. , 2003, Veterinary immunology and immunopathology.

[6]  R. Slocombe,et al.  Outbreak of equine herpesvirus type 1 myeloencephalitis: new insights from virus identification by PCR and the application of an EHV-1 -specific antibody detection ELISA , 2003, Veterinary Record.

[7]  A. Sheoran,et al.  The mucosal humoral immune response of the horse to infective challenge and vaccination with equine herpesvirus-1 antigens. , 2010, Equine veterinary journal.

[8]  C. van Maanen,et al.  Neurological disease associated with EHV-1-infection in a riding school: clinical and virological characteristics. , 2010, Equine veterinary journal.

[9]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[10]  J. Kydd,et al.  Determination of equid herpesvirus 1-specific, CD8+, cytotoxic T lymphocyte precursor frequencies in ponies. , 1999, Veterinary immunology and immunopathology.

[11]  W. D. Wilson,et al.  Equine herpesvirus 1 myeloencephalopathy. , 1997, The Veterinary clinics of North America. Equine practice.

[12]  C. Sweeney,et al.  Equine herpes myeloencephalopathy , 1997 .

[13]  A. Arvin Cell-mediated immunity to varicella-zoster virus. , 1992, The Journal of infectious diseases.

[14]  K. Whitwell,et al.  Pathological findings in horses dying during an outbreak of the paralytic form of Equid herpesvirus type 1 (EHV-1) infection. , 1992, Equine veterinary journal.

[15]  I. Mayhew Large Animal Neurology: A Handbook for Veterinary Clinicians , 1989 .

[16]  B. Rouse,et al.  Herpes simplex virus type 1-specific cytotoxic T lymphocytes recognize virus nonstructural proteins , 1988, Journal of virology.

[17]  C. Kohn,et al.  Equine herpes myeloencephalopathy. , 1987, The Veterinary clinics of North America. Equine practice.

[18]  W A Buurman,et al.  Limiting dilution assays. Experimental design and statistical analysis. , 1987, Journal of immunological methods.

[19]  H. Platt,et al.  Pathological observations on an outbreak of paralysis in broodmares. , 1980, Equine veterinary journal.

[20]  R. Greenwood,et al.  Clinical report of a paralytic syndrome affecting stallions, mares and foals on a thoroughbred studfarm. , 1980, Equine veterinary journal.

[21]  P. Little,et al.  Disseminated Necrotizing Myeloencephalitis: A Herpes-Associated Neurological Disease of Horses , 1976, Veterinary pathology.

[22]  A. Corner,et al.  Meningoencephalomyelitis in Horses Associated with Equine Herpesvirus 1 Infection , 1976, Veterinary pathology.

[23]  T. Jackson,et al.  Paralysis of horses associated with equine herpesvirus 1 infection. , 1971, Journal of the American Veterinary Medical Association.