Paramyxoviridae

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VIRUSES



Introduction

Morphology

  • Single-stranded negative-sense unsegmented RNA virus
  • Reassortment and antigenic shift cannot occur
  • Spike proteins include HN (Haemagglutinin and Neuraminidase) and 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

Virulence

  • Paramyxoviruses replicate in the epithelium of the upper respiratory tract as well as occasionally in the gut

Types and Subtypes

Paramyxoviridae by Species

Overview


Classification


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
  • 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
  • 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 34oC but not at 37oC
      • 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

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 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

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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