Paramyxoviridae

VIRUSES

Morphology

• Single-stranded negative-sense unsegmented RNA virus
• Reassortment and antigenic shift cannot occur
• Spike proteins include
  • HN (Haemagglutinin and Neuraminidase)
  • F (Fusion glycoprotein), which allows the virus to fuse directly to the plasma membrane and release its RNA
    • F also causes syncitium to form, which aids diagnosis
    • Host antibody response to the F protein is the basis for vaccination

Virulence

• Paramyxoviruses replicate in the epithelium of the upper respiratory tract as well as occasionally in the gut
  • Sites of spike protein cleavage
• Virulence varies by virus, see below

Types and Subtypes

Paramoyxoviridae was reclassified in 2000 to include 2 subfamilies and 5 genera:

• Paramoyxovirinae:
  • Bovine Parainfluenza 3
  • Canine Parainfluenza 2
  • Murine Parainfluenza 1 (Sendai virus)
  • Newcastle Disease (NDV) - avian paramyxovirus serotype 1
  • Avian Paramyxoviruses serotypes 2-9
  • Reptilian Paramyxoviruses
  • Mumps
  • Morbilliviruses
    • Canine Distemper (CDV)
    • Rinderpest
    • Pest de petit ruminant (PPR)
    • Measels
    • Seal virus - phocine distemper
    • Dolphin Morbillivirus
    • Hendra virus
    • Nipah virus
• Pneumovirinae
  • Bovine Respiratory Syncytial Virus (BRSV)
  • Turkey Rhinotracheitis Virus

Antigenic Variation

• Antigenic conservation allows some cross protection by vaccination:
  • Conservation of major virus-specific F/HN antigens means vaccines protect against all isolates of the same virus
  • Minor morbillivirus-specific epitopes on F allows some cross protection between canine distemper, measles, and rinderpest
• Antigenic "fingerprinting" is possible for some viruses based on minor variable epitopes of HN, F and NP on specific isolates as detected by monoclonal antibodies
  • These are detected by immunostaining infected cells

Paramyxoviridae by Species

Avian

Newcastle Disease Virus (NDV)

Hosts

• Gallinaceous birds, pigeons, parrots, finches
• Subclinical carriers: ducks, ostriches
• Causes conjunctivitis in humans

Pathogenesis

• Transmission via aerosol and direct contact
• Disease ranges from subclinical respiratory tract infections -> torticollis -> haemorrhages and death

Diagnosis

Two diagnostic tests currently exist:

• Animal test:
  • Samples of trachea and gut of 20 birds are tested in eggs
  • HI using anti-NDV serum (to differentiate HA caused by avian influenza
  • Virulence of isolate tested by the speed it kills chicks
• DNA test (which will soon replace the animal test):
  • Sequencing the cleavage site of H gene
  • The more basic amino acids the more virulent the virus

Control

• Newcastle Disease is NOTIFIABLE
• Vaccination of chickens and racing pigeons
• Surveillance of imported exotic birds
• Isolation of infected stock
• Infected premises to be culled and firebreak cull if spread

Canine

Canine Parainfluenza - 2 (aka Parainfluenza - 5)

Hosts

• Infects dogs

Pathogenesis

• May cause mild upper respiratory infection, rhinitis
• Virus shed for a short time only

Control

• Live attenuated vaccine may be incorporated in multivalent vaccines
• Immunity is short-lived
• Only reduces severity of clinical signs

Secondary Concerns

• Also associated with kennel cough (Infectious canine tracheitis), together with Bordetella bronchiseptica

Canine Distemper Virus (CDV)

Hosts

• Dogs, ferrets, seals, lions, mink
• Has been a major pathogen of dogs prior to vaccination

Pathogenesis

• Variable mortality depending on virulence
• May occur subclinically
• Involvement of central nervous system generally results in death
• Aerosol infection
• Infects alveolar macrophages or oropharynx
• Multiplies in the bronchial and other lymph nodes, infects monocytes and dendritic cells
• Viraemia
• Spreads via monocytes to a variety of epithelium depending upon the strain of virus
• Respiratory and alimentary tracts, skin and later (1-5 wk. post infection) to the brain
• Clinical signs:
  • Mucopurulent oculonasal discharge
  • Keratitis
  • Interstitial pneumonia
  • Severe clinical pneumonia follows secondary infection with Bordetella bronchiseptica
  • Smelly sometimes bloody diarrhoea
  • Eruptions on the skin including hyperkeratosis of the nose and pads (hardpad)
  • Demyelination (especially in cerebellum) -> incoordination or muscle tremors -> paralysis and coma or convulsions -> death
  • Encephalitis
  • Secondary pyogenic infections associated with immunosuppression and damage to epithelia
  • Recovered animals may have persistent or spasmodic chorea
  • The severity of the disease may vary; if enough neutralising antibody develops in the early stages, the virus maybe kept restricted largely to the lymph nodes.

Diagnosis

• May present as series of infections
• Immunocytochemistry of inclusion bodies
  • Intracytoplasmic inclusions may be found in most affected tissues
  • Inclusions persist longest in the brain (may be intranuclear) and the alveolar macrophages
  • Sections of fixed bronchial tissue, lung, macrophages, bladder may be used or nasal or conjunctival epithelium from live animals
• Giant cells may be seen in the alveoli

Control

• Live attenuated virus vaccines given at 10 and 12 weeks of age
  • Some now given at 7 and 10 weeks to allow socialisation
• Homeopathic vaccines do not work
• Live attenuated vaccines may kill some wildlife therefore Iscom vaccine is used in seal sanctuaries

Secondary Concerns

• Can contribute to Infectious canine tracheitis
• May be involved in chronic interstitial pancreatitis
• May cause growth retardation lattice
• May also trigger latent Toxoplasmosis due to suppressing effect on lymphoid tissue

Bovine

Bovine Parainfluenza - 3 (PI-3)

• Virulence varies with isolates
• Cessation of ciliary clearance and epithelial necrosis predisposes to secondary bacterial infections -> cough
• May cause rhinitis of cattle
• With other agents causes calf pneumonia
  • Together with managemental factors (overcrowding, poor ventilation, high humidity, deprivation of colostrum and stress caused by transport or mixing of stock)
• Diagnosis
  • Diseased lung tissue from dead animals or centrifuged cells from lung lavage
  • Virus is too fragile for cell culture isolation (often inactivated intransport)
  • Antigen detection by immunocytochemistry for intracytoplasmic viral inclusions containing labelled viral protein
  • Serology: 4-fold rise in ELISA antibody in paired serum samples from several animals
• Control
  • Improve managemental factors
  • All-in, all-out systems
  • Some vaccination
    • Temperature sensitive mutant that replicates at 34^oC but not at 37^oC
    • Re-infection is common

Bovine Respiratory Syncytial Virus (BRSV)

• Pathogenesis:
  • More serious than PI-3
  • Causes [Respiratory Viral Infections - Pathology#Respiratory syncytial virus|respiratory infection]]
  • Replicates in nasal epithelium -> throughout upper respiratory tract -> bronchial tree
  • Syncytia form -> shed into bronchioles
  • Complications include emphysema and oedema, drop in milk yield in adult cattle
• Epidemiology:
  • Subclinical reinfections are important in spreading disease
  • More than 70% of cattle in the UK have antibodies to BRSV
• Diagnosis is same as for PI-3
• Control
  • Improve husbansry as in PI-3
  • Vaccines are available but not effective as need to stimulate cytotoxic T-cells
• Reference: Bryson, 1999, Update on calf pneumonia, CPD Veterinary Medicine, 1,3, 90-95

Equine

Hendra Virus

• Equine Paramyxovirus
• Causes respiratory infections with respiratory distress and paralysis
• Potentially zoonotic (beware palpating inside the throat for obstruction)

Porcine

Nipah Virus

• Infects pigs and humans
• Humans exposed to pig blood are at risk

Reptiles

Reptilian Paramyxoviruses

• Infect central nervous system and lungs
• Kill particularly snakes
• Healthy reptiles may be carriers
• Testing by serology - HI test
• Aim to keep virus free collection and prevent spread back into the wild

Rodentia

Murine Parainfluenza - 1 (Sendai virus)

• Endemic in many mouse colonies
• Most mice show no symptoms due to maternal antibodies
• But minor respiratory lesions may invalidate carcinogenic or toxicological studies
• Immunological studies also confused due to virus activating NK cells via high circulating IF 3-4 days post-infection
• Control achieved by:
  • Purchasing specific pathogen free (SPF) mice
  • Kill whole colony in an outbreak -> disinfection -> formalin fumigation

Other resources

• On line Paramyxoviridae lecture by P. Russell

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