Herpesviruses

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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
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The elephant herpesvirus Richman et al. 1999.
Science 2831171
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The case of the elephant herpesviruses (Richman
et al. 1999. Science 2831171)
African elephant herpesvirus (cold sores)
Fatal hemorrhagic Disease in Asian elephants
Asian elephant herpesvirus (cold sores)
Fatal hemorrhagic Disease in African elephants
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Viruses with ds DNA genomes
Papovaviridae
bovine herpesvirus-1,2
equine herpesviruses -1,4
Adenoviridae


porcine cytomegalovirus
Herpesviridae

malignant catarrhal fever virus
Poxviridae
African swine fever virus
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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

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Structure
nucleocapsid
envelope
tegument
glycoproteins
(gB, gCgL)
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Productive and latent infections
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Latency and Reactivation
Viral DNA
LAT
IE genes (regulatory) E genes (enzymes) L genes
(structural)
reactivation
stress immunosuppression corticosteroids cAMP
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Bovine herpesviruses
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BHV-1(IBR virus)

• Infectious bovine rhinotracheitis
• Disseminated fatal disease of newborns
• Abortions
• Genital lesions
• Encephalitis

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Infection in the animal
Infection of

replication in
reactivation
susceptible animal
epithelial cells
from
latency
replication in

epithelial cells
(rhinotracheitis)
systemic
cell-associated
spread
infection of the fetus
encephalitis
- abortion
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Primary lesion
chemokines
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Clinical and immunological parameters
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Complications of BHV-1 infection

• abortions
• encephalitis
• fatal disease in newborn calves
• Shipping fever (M. hemolytica, P. multocida)
• Bronchopneumonia - fibrinous pleuropneumonia

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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

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Diagnosis of BHV

• virus isolation
• immunofluorescence
• immunohistochemistry
• PCR
• serology
• virus neutralization
• ELISA

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Vaccination against BHV-1

• modified-live (attenuated)
• intra nasal
• intra muscular
• inactivated
• intra muscular

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

• 9 types, 1,3 and 4 are of veterinary importance

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EHV-1 and EHV-4

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

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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

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EHV-1 associated neurological disease - An
emerging disease
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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 38283 )

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Risk factors for EHV-1 myeloencephalitis

• Viral (Nugent et al. 206. J. Virol 804047
• N752D mutation
• Host (Goehring et al. 2006. J. Vet. Int. Med.
  20601)
• sex - female
• age - 3 yrs
• season - fall, winter
• fever
• breed - Hispanic, Standardbred, Draught

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Viraemia by neuropathogenic and
non-neuropathogenic EHV-1
Allen and Breathnach 2006. Eq Vet Jn 38252
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EHV-1 abortions

• late in gestation (7th to 11th month)
• few weeks to several months after respiratory
  outbreak
• abortion storms

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

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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??

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Other herpesviruses

• alpha herpesviruses
• porcine herpesvirus 1 (pseudorabies/Aujeszkys
  disease)
• Canine herpesvirus
• Feline herpesvirus
• Mareks disease
• beta herpesviruses
• porcine cytomegalovirus
• gamma herpesviruses
• malignant catarrhal fever

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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

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canine herpesvirus

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

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feline herpesvirus

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

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Mareks 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

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beta herpesvirus - porcine cytomegalovirus

• asymptomatic if endemic in herds
• in susceptible herds
• inclusion body rhinitis
• fetal death
• runting, poor growth in young piglets

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

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acute MCF