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Herpesviruses ubiquitous, all vertebrate species ds DNA, approximately 100 genes co-evolved with their hosts, well adjusted enveloped latent infections The case of the elephant herpesviruses

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

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

The case of the elephant herpesviruses (Richman et al. 1999. Science 283:1171): 

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

Viruses with ds DNA genomes: 

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


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


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


Productive and latent infections


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

Bovine herpesviruses: 

Bovine herpesviruses

BHV-1(IBR virus): 

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

Infection in the animal: 

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

Primary lesion: 

Primary lesion chemokines

Clinical and immunological parameters: 

Clinical and immunological parameters

Complications of BHV-1 infection: 

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

Factors contributing to shipping fever: 

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

Diagnosis of BHV: 

Diagnosis of BHV virus isolation immunofluorescence immunohistochemistry PCR serology virus neutralization ELISA

Vaccination against BHV-1: 

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

Vaccines for eradication: 

Vaccines for eradication gB gB gB gB gene for gE deleted gE gB infected vaccinated ELISA for antibodies infected vaccinated gD subunits gE gD gD gD

Equine herpesviruses: 

Equine herpesviruses 9 types, 1,3 and 4 are of veterinary importance

EHV-1 and EHV-4: 

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

EHV-1 and EHV-4 (respiratory disease): 

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

EHV-1 associated neurological disease - An emerging disease: 

EHV-1 associated neurological disease - An emerging disease

Myeloencephalopathy by EHV-1: 

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 Borchers et al. 2006. Eq Vet Jn 38:283 )

Risk factors for EHV-1 myeloencephalitis: 

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

Viraemia by neuropathogenic and non-neuropathogenic EHV-1: 

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

EHV-1 abortions: 

EHV-1 abortions late in gestation (7th to 11th month) few weeks to several months after respiratory outbreak abortion storms

Pathogenesis of abortion: 

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

Pathogenesis of abortion: 

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

Circulatory immune responses: summary: 

Circulatory immune responses: summary strong humoral response to infection with transient CF and longer lived VN antibody responses (Thompson et al. 1976) protection from reinfection is short lived (Allen and Bryans 1986) no correlation between circulating antibody levels and protection from re-infection (Hannant et al. 1993; Mumford et al. 1994) MHC I restricted CD8+ CTL responses are generated in response to infection (Allen et al. 1995)

Prevention of EHV-1 disease: 

Prevention of EHV-1 disease management vaccines short-lived immunity (mares - 5,7,9 months of gestation reduce severity but do not prevent exacerbate myeloencephalitis??

Other herpesviruses: 

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

porcine herpesvirus: 

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

canine herpesvirus: 

canine herpesvirus wide-spread, usually asymptomatic generalized fatal disease in puppies (fading puppy syndrome) hypothermia no vaccine in N. America

feline herpesvirus: 

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

Marek’s disease: 

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

beta herpesvirus - porcine cytomegalovirus: 

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

malignant catarrhal fever (gamma herpesvirus): 

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

clinical signs in susceptible species: 

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

acute MCF: 

acute MCF

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