1. Case AP07-2606 Danielle L. Brown NC State University, College of Veterinary Medicine Co-presenters: Dr. Talmage Brown, Dr. James Guy Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

2. History and PE Findings 7-year-old Paint Horse mare 7-year-old Paint Horse mare Presented for 2 day history of colic, anorexia, and depression Presented for 2 day history of colic, anorexia, and depression Normal TPR Normal TPR Rectal examination within normal limits Rectal examination within normal limits Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

3. Clinical Pathology Data and Case Progress CBC: Leukopenia with neutropenia and lymphopenia, thrombocytopenia CBC: Leukopenia with neutropenia and lymphopenia, thrombocytopenia Chemistry panel: Elevated liver enzymes (ALP, AST, GGT, Bilirubin), Elevated CK Chemistry panel: Elevated liver enzymes (ALP, AST, GGT, Bilirubin), Elevated CK Next morning: Next morning: Dyspnea, mucopurulent nasal discharge Dyspnea, mucopurulent nasal discharge Toxic mucous membranes Toxic mucous membranes Very uncomfortable Very uncomfortable Laterally recumbent Laterally recumbent Humanely euthanized and submitted for necropsy Humanely euthanized and submitted for necropsy Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

4. Gross examination Moderate subcutaneous edema Moderate subcutaneous edema Intestinal serosal petechiae and ecchymoses Intestinal serosal petechiae and ecchymoses Hepatic blood vessels prominent and congested Hepatic blood vessels prominent and congested Several small strongyles within large colon Several small strongyles within large colon Lungs: Lungs: Failed to collapse Failed to collapse Mottled appearance with coalescing slightly firm white foci Mottled appearance with coalescing slightly firm white foci Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

12. Morphologic Diagnosis Liver: Multifocal to coalescing, severe, acute hepatic necrosis with intranuclear inclusion bodies and fibrinoid vascular necrosis Liver: Multifocal to coalescing, severe, acute hepatic necrosis with intranuclear inclusion bodies and fibrinoid vascular necrosis Etiology: Equine herpesvirus-4 isolated from liver and kidney Etiology: Equine herpesvirus-4 isolated from liver and kidney Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

13. EHV-1 vs EHV-4 Show considerable cross-reactivity Show considerable cross-reactivity Until 1981 were considered as subtypes of same virus Until 1981 were considered as subtypes of same virus Both are endemic in horse populations worldwide Both are endemic in horse populations worldwide Horses are repeatedly infected by both viruses in nature and disease signs become less severe with progressive episodes later in life Horses are repeatedly infected by both viruses in nature and disease signs become less severe with progressive episodes later in life Both cause rhinopneumonitis Both cause rhinopneumonitis EHV-1 is main cause of abortions, paresis, and neonatal foal deaths EHV-1 is main cause of abortions, paresis, and neonatal foal deaths Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

14. Pathogenesis Mainly transmitted through inhalation Mainly transmitted through inhalation Virus first replicates in upper respiratory epithelium and local lymph nodes Virus first replicates in upper respiratory epithelium and local lymph nodes Results in leukocyte-associated viremia Results in leukocyte-associated viremia Virus later replicates within endothelial cells Virus later replicates within endothelial cells Latency in lymphoid and neural tissues demonstrated for both viruses Latency in lymphoid and neural tissues demonstrated for both viruses Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

15. Unusual presentations of equine herpesvirus infection Neonatal mortality due to EHV-4 in a foal (O’Keefe et al, 1995) Necrosis and intranuclear inclusions seen in lung, liver and small intestinal mucosa PCR detected EHV-4 Disseminated EHV-1 infection in a 2-year-old filly (Hamir et al, 1994) Random necrosis seen in lung, liver, spleen, and adrenal glands with numerous intranuclear inclusion bodies Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

16. Acknowledgements Dr. Talmage Brown Dr. James Guy Sandra Horton and rest of NCSU-CVM histology laboratory staff Resident mates and senior pathologists Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

17. Questions? Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

18. References Reed SM and Toribio (2004) Equine herpesvirus 1 and 4. Vet Clin Equine 20:631-642. Hamir AN et al (1994) Disseminated equine herpesvirus-1 infection in a 2-year-old filly. JVDI 6:493-496. O’Keefe JS et al (1995) Neonatal mortality due to equid herpesvirus 4 (EHV-4) in a foal. Aust Vet J 72:353-354. Patel JR and Heldens J (2005) Equine herpesviruses 1 (EHV- 1) and 4 (EHV-4) – epidemiology, disease and immunoprophylaxis: a brief review. Vet J 170:14-23. van Maanen C (2002) Equine herpesvirus 1 and 4 infections: an update. Vet Q 24:58-78. Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only