Herpesviridae

VIRUSES

Introduction

Herpes viruses are some of the more difficult viruses to combat as they quite contentedly go latent for long periods of time. They often produce an initial respiratory response but go subclinical until the animal becomes immunosuppressed. Protection against herpes is challenging, as immunity relies on stimulating a CD8+ T-cell response, which is difficult to provoke by conventional vaccination.

Morphology

• Double stranded DNA that becomes a closed circle in the host nucleus
• Remains unintegrated while latent

Virulence and Pathogenesis

• Three types of genes involved in replication:
  • Immediate early genes (IE genes): strong promoter of the expression of adjacent viral genes
  • Early genes: stimulate viral DN replication; potential cause of lymphoproliferation and tumors in the absence of cell lysis
  • Late genes: encode viral structural proteins
    • Cause large intranuclear inclusion bodies typical of herpes viruses as capsid proteins are assembled
    • Envelope buds through nuclear membrane, containing spike glycoproteins (gA to gE)
    • Masses of virus then either lyse or fuse cells, causing ulceration, etc.
• Initial replication in respiratory tract
• Spread determines pathogenicity:
  • Cell-associated spread means that virus is spread by cell fusion
  • Can target crucial tissues: brain, placenta, etc
• All become latent and reactivate under stress
• Reactivation is associated with the presence of thymidine kinadse (tk) gene (which is deleted in GE vaccines)
  • Accelerates DNA synthesis

Research

• Some herpes and pox viruses express non-structural proteins known as virokines
• Virokines appear to help the virus evade the Th-1 response by altering the inflammatory response

Virus by Species

Virus	Abbreviation	Clinical signs
Equine Herpesvirus 1	EHV1	Respiratory disease, abortion, paresis
Equine Herpesvirus 2	EHV2	Avirulent
Equine Herpesvirus 3	EHV3	Pustular lesions on genitalia
Equine Herpesvirus 4	EHV4	Mild respiratory disease
Bovine Herpesvirus 1 Infectious Bovine Rhinotracheitis Virus Infectious Pustular Vulvo Vaginitis	BHV 1 IBVR IPVV	IBRV: Upper respiratory disease, abortion IPVV: Irritant pustular lesions on genitalia
Bovine Mammilitis Virus	BHV2 (BHMV)	Erosive lesions on teat and udder
Malignant Catarrhal Fever Virus	MCFV	Infection of eye and upper respiratory
Suid Herpesvirus 1 (Pseudorabies)	PSV	Respiratory disease, abortion (CNS in piglets, pruritis in cattle)
Suid Herpesvirus 2 (Porcine Cytomegalovirus)	PCMV	Subclinical, atrophic rhinitis
Canine Herpesvirus 1	CHV1	Fading puppies, repro failure
Feline Herpesvirus 1	FHV1	Rhinitis, bronchitis
Channel Catfish virus		Death with hemorrhage
Koi herpes		Death with gill necrosis
Herpesvirus cyprini		Carp pox, also in goldfish
Elephant endotheiliotropic herpes virus		African elephant: mild, skin papillomas Indian elephant: FATAL with hemorrhage
Gallid Herpesviru 1	MDV	Lymphoproliferative, invades CNS, visceral tumors
Gallid Herpesvirus 2	HVT	Avirulent, protective
Gallid Herpesvirus 3 (Infectious Laryngo-tracheitis)	AHV1 (ILT)	Tracheitis and bronchitis
Duck Plague Virus		Endothelial and enteric lesions
Pigeon Herpesvirus		Respiratory disease
Psittacid and Raptor Herpes		Death with yellow diarrhoea and coma
Monkey B virus		Potential zoonosis; oral ulcers in Asiatic monkeys, fatal encephalitis in man

• Equine herpes virus 1 and 4 in rhinitis, see respiratory infections
• Canine herpes virus 1 in respiratory disease

• In skin infections
  • Bovine herpes virus 1, 2 4
  • Equine herpes virus 3
  • Feline herpes virus 1

Feline herpesvirus -1

• Feline viral rhinotracheitis in rhinitis, see respiratory infections
  • One of the causes of Feline viral rhinotracheitis
    • Viruses and bacteria are involved in the complex. The most frequent aetiologic agent is FHV-1, and less frequently feline calicivirus and/or Chlamydophia psittaci (NB: previously called Chlamydia psittaci var felis)
    • All three agents infect URT respiratory epithelium, although FHV-1 has the highest affinity for this epithelium
    • Feline calicivirus more frequently infects the oral mucosa -> ulcerative stomatitis
    • C.psittaci more frequently infects the conjunctival epithelium -> chronic conjunctivitis
    • Infection of the respiratory epithelium by FHV-1 results in a typical neutrophilic rhinitis with intraepitheial intranuclear eosinophilic inclusion bodies, with expected clinical signs
    • Resolution of clinical signs usually occurs by 7-14 days.
    • FHV-1 remains latent in the trigeminal ganglion, and can reactivate at times of stress. Can infect the cornea -> ulcerative keratitis.
    • Occasional mortality in kitten or immunocompromised animals usually associated with secondary bacterial infection.

Bovine herpesvirus -1

• Bovine herpesvirus - 1 (Infectious bovine rhinotracheitis virus) contributes to undifferentiated neonatal calf diarrhoea, a mixed viral enteritis in calves; and rhinitis
• Causes Infectious bovine rhinotracheitis (IBR)
• Highly infectious URT disease of cattle
• High morbidity, low mortality
• Aerosol transmission - requires close contact between animals
• BHV-1 infects the respiratory mucosal epithelial cells (intranuclear inclusion eosinophilic inclusion bodies)from nasal mucosa down to bronchioles
  • leading to neutrophilic inflammation of varying severity.... serous -> catarrhal -> purulent nasal discharge, sneezing, coughing.
  • with secondary bacterial infection (eg: Pasturella spp., Mycoplasma spp., Fusobacterium necrophorum) can lead to fibrinous to necrotizing inflammation; mucosal sloughing, ulceration... pyrexia, dyspnoea ... inhalation pneumonia... death.
• Clinical signs include coughing, discharge, lacrimation, and increased respiratory rate.
• Clinical disease most severe in young calves - can develop mucosal ulcerative lesions in the oesophagus and forestomachs and viraemia with multiorgan infection.
• Cause of abortion >5 months of gestation

• Also causes infectious vulvovaginitis/balanoposthitis and meningoencephalitis
• May contribute to Enzootic pneumonia of calves

Inclusion body rhinitis (porcine cytomegalovirus)

• in rhinitis and sometimes in atrophic rhinitis progressing to pneumonia, see Inclusion body rhinitis

• Cytomegaloviruses
  • Porcine cytomegalovirus
    • Causes Inclusion body rhinitis
      • Disease of suckling piglets 1-5 wks of age
      • Clinical signs: those associated with acute/subacute rhinitis (ie: serous nasal discharge, progressing to catarrhal or purulent discharge with time and secondary bacterial infections; sneezing; pyrexia)
      • Morbitity high, mortality low
      • Histology: large basophilic intranuclear inclusion bodies in the nasal and sinus respiratory epithelium with lymphocytic infiltration of the mucosa.
      • Can develop viraemic stage, with inclusions in other organs eg: renal tubular epithelium. Piglets can die during this phase.

Gammaherpesviridae

Alcephaline-1 Virus