Paramyxoviridae

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Overview

• Systemic infections - controlled by live monotypic vaccination
• Respiratory infections - not controled by live monotypic vaccinations
• On line Paramyxoviridae lecture by P. Russell

Classification

• Paramyxovirinae
  • 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

Virus properties

Structure

• Negative sense RNA, unsegmented, single stranded
  • -> Reasortment and antigenic shift cannot occur
• HN spike contains:
  • Haemagglutinin (H)- attachment protein
  • Neuraminidase (N)
• Fusion glycoprotein (F) spike
  • -> Viral lipid bilayer can fuse directly with host plasma membrane
    • -> RNA released into cytoplasm
  • ->Syncytium (multinucleated giant cells) in lesions and cell culture
  • Host antibody response to this protein is most important
    • Best induced by live attenuated vaccines

Growth in vitro

• Allantoic cavity of 10-day-old eggs
• Followed by haemagglutination

In vivo

• Cell tropism for upper respiratory tract epithelium
  • All replicate in these cells
• Some replicate in the gut
• Most virulent replicate in lymphoid cells and neurons (Distemper, NDV)
• Links to the readiness to cleave Fo and Ho precursors in different cells

Antigenic differentiation

• Major conserved immunodominant virus-specific antigens on F and HN
  • -> Vaccines protect against all isolates of the same virus
• Minor morbillivirus-specific epitopes on F
  • Some crossprotectin between canine distemper, measels and rinderpest
• Minor variable epitopes of F, HN and NP
  • Allows antigenic fingerprinting

Newcastle Disease Virus (NDV)

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

• Virulence
  • Disease ranges from subclinical respiratory tract infections -> torticollis -> haemorrhages and death

• Epidemiology
  • Air-born
  • Direct contact of poultry

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

• Control
  • Isolation of stock
  • Vaccination of chickens and racing pigeons
  • Surveillance of imported exotic birds
  • Notifiable disease
  • Infected premises to be culle and firebreak cull if spread

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

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

Canine Parainfluenza - 2

• or Parainfluenza - 5
• Infects dogs
• May cause mild upper respiratory infection, rhinitis
  • Virus shed for a short time only
• Also part of kennel cough (Infectious canine tracheitis), together with Bordetella bronchiseptica
• Control:
  • Live attenuated vaccine may be incorporated in multivalent vaccines
    • Immunity is short-lived
    • Only reduces severity of clinical signs

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 [Viral infections#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

Canine Distemper Virus (CDV)

• Hosts: dogs, ferrets, seals, lions, mink
• Has been a major pathogen of dogs prior to vaccination
• Variable mortality depending on virulence
• May occur subclinically
• Involvement of central nervous system generally results in death
• Pathogenesis:
  • Aerosol infection
  • Infects alveolar [[General Pathology - Chronic Inflammation#Macrophages|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

• 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

Hendra Virus

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

Nipah Virus

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

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