1. Herpesviruses September 9,14, 2010

2. Shanthi and Kumari, December 1993 –April 1995 Smithsonian National Zoological Park, Washington

3. The elephant herpesvirus Richman et al. 1999. Science 283:1171

4. The case of the elephant herpesviruses (Richman et al. 1999. Science 283:1171) Asian elephant herpesvirus (“cold sores”) Fatal hemorrhagic Disease in African elephants African elephant herpesvirus (“cold sores”) Fatal hemorrhagic Disease in Asian elephants

5. Viruses with ds DNA genomes Poxviridae African swine fever virus Herpesviridae Adenoviridae Papovaviridae bovine herpesvirus-1,2 porcine cytomegalovirus equine herpesviruses -1,4 malignant catarrhal fever virus

6. Herpesviridae Alphaherpesvirinae (BHV-1, EHV-1,4, FelineHV, CanineHV) –Grow rapidly –Latency in sensory neurons Betaherpesvirinae –Cytomegaloviruses (large balloon-like cells) –Grow slowly –Latency in salivary glands, kidneys, lymphocytes Gammaherpesvirinae (malignant catarrhal fever virus) –Lymphoproliferative diseases –Latency in lymphoid cells

7. Structure nucleocapsid envelope tegument glycoproteins (gB, gC…gL)

8. Productive and latent infections

9. Viral DNA Latency and Reactivation LAT IE genes (regulatory) E genes (enzymes) L genes (structural) stress immunosuppression corticosteroids cAMP reactivation

10. Bovine herpesviruses TypeClinical entity BHV-1.1respiratory (IBR), abortions BHV-1.2genital (IPV) BHV-1.3 (5)emcephalitis BHV-2mammalitis Bovine herpesvirusClinical BHV-1.1Respiratory (IBR), abortions, encephalitis BHV-1.2Genital lesions (IPV) BHV-1.3 (5)Encephalitis BHV-2Mammalitis

11. BHV-1(IBR virus) Infectious bovine rhinotracheitis Disseminated fatal disease of newborns Abortions Genital lesions Encephalitis

12. Infection in the animal reactivation from latency replication in epithelial cells (rhinotracheitis) Infection of susceptible animal establishment of latency (infection for the first time) systemic cell-associated spread infection of the fetus -> abortion encephalitis replication in epithelial cells

13. Clinical and immunological parameters

14. Complications of BHV-1 infection abortions encephalitis fatal disease in newborn calves Shipping fever (M. hemolytica, P. multocida) –Bronchopneumonia -> fibrinous pleuropneumonia

15. Factors contributing to shipping fever environmental –crowding animals from different sources –stress host-virus –paralysis of mucociliary escalator –release of iron and nutrients –increased colonization –immunosuppression

16. Diagnosis of BHV virus isolation immunofluorescence immunohistochemistry PCR serology –virus neutralization –ELISA

17. Vaccination against BHV-1 modified-live (attenuated) –intra nasal –intra muscular inactivated –intra muscular

18. Equine alpha herpesviruses 5 other known herpesviruses Equine herpesvirusClinical EHV-1Respiratory, abortions, encephalomyelitis EHV-3Genital lesions (coital exanthema) EHV-4Respiratory EHV-9Asymptomatic in equids, severe disease in other species

19. EHV-1 and EHV-4 Immunologically related Respiratory disease EHV-1causes abortions, neurological disease Immunity short lived Reinfection or reactivation

20. EHV-1 and EHV-4 (respiratory disease) Incubation period (1-10 days) Primary infection in young horses Biphasic fever Nasal discharge, cough Uncomplicated cases -> complete recovery 1-2 weeks

21. EHV-1 associated disease Acute respiratory disease in young horses Abortions (3 rd trimester but can also occur at other times) Myeloencephalopathy (EHM)

22. EHV-1 associated neurological disease - An emerging disease ?

23. Myeloencephalopathy by EHV-1 often but not always associated with respiratory disease often several horses sudden onset rapid progression, early stabilization ataxia, paresis, urinary incontinence, cystitis little evidence of viral replication in neural tissues (immune mediated?) vasculitis, thrombosis, hemorrhages (See EHV-1 Consensus Statement. J Vet Int Med. 2009. 23:450-461)

24. Risk factors for EHV-1 myeloencephalitis Viral (Nugent et al. 206. J. Virol 80:4047 –N752D mutation Host (Goehring et al. 2006. J. Vet. Int. Med. 20:601) –sex - female –age - > 3 yrs –season - fall, winter –fever –breed - Hispanic, Standardbred, Draught

25. Goodman et al. 2007. A point mutation in a herpesvirus polymerase determines neuropathogenecity. PLoS Pathogen. 3(11):e160.doi.1371

26. Viraemia by neuropathogenic and non-neuropathogenic EHV-1 Allen and Breathnach 2006. Eq Vet Jn 38:252

27. EHV-1 abortions third trimester most likely few weeks to several months after respiratory outbreak abortion storms

28. Pathogenesis of abortion viraemia endometrial endothelial cell infection endometrial vasculitis and thrombosis extensive infarction: virus negative fetus

29. Pathogenesis of abortion viraemia endometrial endothelial cell infection endometrial vasculitis and thrombosis extensive infarction: virus negative fetus limited infarction: virus positive fetus

30. Prevention of EHV-1 disease management vaccines –short-lived immunity (mares - 5,7,9 months of gestation) –reduce severity but do not prevent –no vaccines licensed to prevent encephalomyelitis

31. Diagnosis Virus isolation PCR Type 1 vs 4 D752 vs N752 serology

32. Prevention and Control

33. Other herpesviruses alpha herpesviruses –porcine herpesvirus 1 (pseudorabies/Aujeszky’s disease) –Canine herpesvirus –Feline herpesvirus –Marek’s disease beta herpesviruses –porcine cytomegalovirus gamma herpesviruses –malignant catarrhal fever

34. porcine herpesvirus endemic in most parts of the world - Canada considered free (reportable disease) wide host range pigs –asymptomatic –abortions –fatal disease in new born piglets –respiratory, neurological other species

35. canine herpesvirus wide-spread, usually asymptomatic generalized fatal disease in puppies (fading puppy syndrome) Ocular (Ledbetter, 2009. Vet Ophthalmol. 12:242-7) hypothermia no vaccine in N. America

36. feline herpesvirus feline rhinotracheitis wide spread in catteries respiratory infections abortions - no direct viral involvement vaccines

37. Marek’s disease lymphoproliferative, neurological disease of young chickens unilateral paralysis, ataxia due to infiltration of spinal nerves involvement of iris, skin stable in feather follicle dander

38. beta herpesvirus - porcine cytomegalovirus asymptomatic if endemic in herds in susceptible herds –inclusion body rhinitis –fetal death –runting, poor growth in young piglets

39. malignant catarrhal fever (gamma herpesvirus) other ruminants ? other species malignant catarrhal fever

40. clinical signs in susceptible species peracute –high fever, diarrhoea, death in 1-3 days acute –fever, depression, enlarged lymph nodes, serous nasal discharge, erosive lesions, corneal opacity, high mortality chronic form

41. acute MCF