Introduction

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

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

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 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

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.

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

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

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

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

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