Week 7

• Herpesviridae

  Enveloped, spherical to pleomorphic
• Herpesviridae

  • Tegument
  • Capsid surrounded by layer of globular material
  • Double-stranded DNA genome
• Herpesviridae Viral replication

  1. DNA replication and encapsidation occurs in nucleus

  2. Viral envelope acquired by budding through inner layer of nuclear envelope

  3. Mature virions accumulate within vacuoles in cytoplasm

  4. Released by exocytosis or cytolysis
• Herpesviridae don't survive outside of host

  Moist, cool environmental conditions promote extended survival of Herpesviridae
• Latently infected animals serve as reservoirs for Herpesviridae

  Persistent infection - periodic or continous shedding
• Some Herpesviridae are oncogenic
• Factors that can reactivate latent Herpesviridae infections

  • Stress
  • Intercurrent infections
  • Shipping
  • Cold
  • Crowding
  • Administration of glucocorticoid drugs
• Herpesviridae

  • Eosinophilic intranuclear inclusion bodies
  • Type A cowdry bodies
  • Formation of syncytium
• Alphaherpesvirinae

  • Generally highly cytopathic in cell culture
  • Relatively short replication cycle
  • Produce localized lesions on skin or mucosae of respiratory and genital tracts
  • Can cause generalized infections with foci of necrosis in almost any organ or tissue, typical of infection of very young or immunocompromised animals
• Bovine herpesvirus 1

  • 3 subtypes: BHV-1.1 (respiratory), BHV-1.2 (genital subtype)
  • Transmission via droplet, respiratory disease and conjunctivitis, or coitus/artificial insemination with infective semen, causing genital disease
• Clinical signs of bovine herpesvirus 1 respiratory disease

  • Rhinitis, laryngitis, tracheitis
  • Inflamed nares giving red nose appearance due to hyperemia
  • Grayish necrotic foci
  • Nasal discharge that is serous and mucopurulent
  • Fibronecrotic rhinitis
  • Uncomplicated cases recover in 10-14 days
  • Complications from secondary bacterial infection (Mannheimia hemolytica, Pasteurella multocida)
• Clinical signs of bovine herpesvirus 1 genital disease

  • Infectious pustular vulvovaginits after coitus, with frequent urination, tail held elevated, vaginal mucosa red and swollen, mild vaginal discharge, vulva swollen with red spots and discrete pustules
  • Balanoposthitis with inflammation and pustules in mucosa of penis and prepuce
• Ocular form of bovine herpesvirus 1

  • Conjunctivitis common finding in typical "red nose", with lesions confined to conjunctiva and no lesions on cornea
• Abortion is a common sequel to natural bovine herpesvirus 1 infection, and can also occur as a result of some modified-live virus vaccines in animals in contact with IBR-susceptible pregnant animals
• Systemic disease of newborn calves with bovine herpesvirus 1

  • Severe in calves less than 10 days of age, often fatal, infected in-utero or right after birth
• Bovine herpesvirus 1 vaccines

  • Modified live vaccines
  • Subunit vaccine
  • Inactivated vaccines (parenteral to stimulate humoral antibodies, may cause abortion in pregnant cows; intranasal to stimulate humoral antibodies, safe to use in pregnant cows)
  • Live attenuated
• Bovine herpesvirus 2

  Causes bovine ulcerative mammillitis in cattle, usually within 2 weeks of calving, transmitted by trauma to skin, direct contact, fomite mediated, or mechanical transmission by stable flies
• Clinical signs of bovine herpesvirus 2 infection

  • Severe cases have painful, swollen teat with bluish skin that exudes serum and forms raw ulcers, high incidence of mastitis
• Pseudo-lumpy skin disease

  Caused by bovine herpesvirus 2 in cattle in southern Africa, transmitted mechanically by arthropods, causes mild fever and sudden appearance of skin nodules on face, neck, back, and perineum
• Equine herpesvirus 1

  • Endemic in horse populations around the world
  • transmitted by inhalation of infected aerosols or direct/indirect contact with nasal discharge, aborted fetuses, placenta, or placental fluids
  • Can establish latent infections in tissues of CNS and lymph system without causing clinical symptoms, reactivated in immunosuppressed horses causing disease or viral shedding
• Pathogenesis of equine herpesvirus 1

  1. Infects epithelial cells in respiratory tract, spreads to local lymph nodes, infects leukocytes causing cell-associated viremia, establishes latent infections in T lymphocytes and trigeminal ganglion neurons

  2. Reactivation leads to shedding of virus from nasal epithelium and uterine infection, spreads to and infects endothelial cells lining blood vessels leading to vasculitis, thrombosis, and ischemia
• Clinical forms of equine herpesvirus 1

  • Respiratory disease affects mostly younger horses
  • Encephalomyelopathy affects horses of any age or breed
  • Reproductive form causes abortion, usually sporadic but can occur in abortion storms with large numbers of susceptible mares exposed
• Equine herpesvirus 4

  Causes equine viral rhinopneumonitis, transmitted by droplet infection from infected or inapparently shedding horses

  less severe tissue destruction than EHV-1, rarely causes abortion, rarely results in viremia

  upper respiratory tract disease - rhinopharyngitis, tracheobronchitis
• Equine herpesvirus vaccines

  • Live-attenuated
  • Inactivated
  • Combined vaccines that include EHV-1 & EHV-4
  • Ideally prevent early infection of foals and latency in pregnant mares, but immunity is short-lived
• Porcine herpesvirus 1 (Pseudorabies)


  • Infects pigs as primary hosts, but can also infect secondary hosts like horses, cattle, sheep, goats, dogs, and cats with hyperacute, rapid, and high mortality disease, while humans are refractory
  • Recovered pigs are latent carriers for life, and rodents can also act as reservoirs transmitting disease between farms
  • Virus is shed in saliva, nasal discharge, and milk of infected pigs, and can be transmitted by various routes including ingestion, aerosol, and direct contact
• Pathogenesis of porcine herpesvirus 1 in pigs

  Primary replication in upper respiratory tract, tonsils, and nasopharynx, then spread via lymphatics to regional lymph nodes, brief viremia with virulent strains, localization in different organs including CNS via cranial nerve axons with preference for neurons of pons and medulla
• Porcine herpesvirus 1 infection in pigs

  • Nonimmune piglets have 100% mortality rate
  • nonimmune pregnant sows have 50% mortality rate, infection before 30 days gestation causes death and resorption of embryo, infection in late pregnancy causes mummified, macerated, stillborn, weak, or normal piglets with up to 20% of sows aborting older pigs have mild disease with <2% mortality
• Clinical signs of porcine herpesvirus 1 in secondary hosts

  • Cattle have intense pruritus (itching), progressive CNS involvement, and death from respiratory failure
  • Dogs have frenzy associated with pruritus, self-mutilation, paralysis of jaws and pharynx
  • Cats have rapidly progressive disease with pruritus
• Porcine herpesvirus 1 vaccines

  • Recombinant DNA
  • Deletion mutant
  • Live-attenuated
  • Inactivated
• Feline herpesvirus 1

  • One of the two most common causes of infectious respiratory disease in cats, along with feline calicivirus
  • Transmitted by shedding in ocular, nasal, and oral secretions, with all recovered cats becoming latent carriers that can reactivate and shed virus in oronasal or conjunctival secretions
• Pathogenesis of feline herpesvirus 1

  Replicates in mucosa of nasal septum, turbinates, nasopharynx, and tonsils

  restricted to areas of low temperature in upper respiratory tract, rarely causes viremia

  infection leads to areas of multifocal epithelial necrosis, inflammation, and fibrinous exudate
• Clinical signs of feline herpesvirus 1

  • Kittens up to 4 weeks have severe upper respiratory disease, extensive rhinotracheitis, and fatal bronchopneumonia from secondary bacterial infection, as well as conjunctivitis and ulcerative keratitis
  • Cats over 6 months have mild or subclinical disease
  • Pregnant queens may abort around 6th week of pregnancy, likely due to severe systemic effects rather than placental transmission
• Feline herpesvirus 1 vaccines

  • Modified live virus (parenteral and intranasal)
  • Inactivated vaccine (parenteral)
• Canine herpesvirus 1

  Causes hemorrhagic disease of puppies (fading puppy syndrome), highly fatal generalized hemorrhagic disease
• Pathogenesis of canine herpesvirus 1 in puppies

  1. In-utero infection can cause abortion, stillbirth, or infertility

  2. Systemic neonatal infection develops within 9 days of birth, with initial replication in nasal epithelium, tonsils, and pharynx followed by mucosal invasion and leukocyte-associated viremia, leading to diffuse necrotizing vasculitis, multiple hemorrhagic necrosis, thrombocytopenia, and disseminated intravascular coagulation

  3. CNS infection results in meningoencephalitis
• Transmission of canine herpesvirus-1 (CHV-1) in puppies

  • Contact with infected oral, nasal, or vaginal secretions of dam
  • In-utero transmission
  • From passage through birth canal
  • Contact with secretions of littermates & infected fomites
• Transmission of CHV-1 in older dogs

  • Venereal transmission
  • Contact with saliva, nasal discharge, or urine of infected dogs or puppies
• Pathogenesis of CHV-1 in-utero infection

  abortion, stillbirth, infertility

  develop systemic infection if survives
• Factors governing systemic neonatal CHV-1 infection

  • Body temperature - CHV-1 replicated optimally at 33, pup critically dependent on ambient temperature and maternal contact
  • Maternal immunity - Maternal antibodies provide protection, pups borns from seronegative bitches highly vulnerable
• Clinical signs of CHV-1 in puppies

  • Painful crying
  • Abdominal pain
  • Anorexia
  • Dyspnea
  • Passing soft, odorless, greenish stool
  • No elevation in body temperature