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#REDIRECT[[:Category:Paramyxoviridae]]
<big><center>[[Viruses|'''BACK TO VIRUSES''']]</center></big>
 
 
===Overview===
 
*Systemic infections - controlled by '''live monotypic vaccination'''
*Respiratory infections - ''not'' controled by '''live monotypic vaccinations'''
*[http://www.pitt.edu/~super1/lecture/lec3401/index.htm On line Paramyxoviridae lecture by P. Russell]
 
 
===Classification===
 
*'''Paramyxovirinae'''
**[[Paramyxoviridae#Bovine Parainfluenza - 3 (PI-3)| Bovine Parainfluenza 3]]
**[[Paramyxoviridae#Canine Parainfluenza - 2|Canine Parainfluenza 2]]
**[[Paramyxoviridae#Murine Parainfluenza - 1 (Sendai virus)|Murine Parainfluenza 1 (Sendai virus)]]
**[[Paramyxoviridae#Newcastle Disease Virus (NDV)|Newcastle Disease (NDV)]] - avian paramyxovirus serotype 1
**Avian Paramyxoviruses serotypes 2-9
**[[Paramyxoviridae#Reptilian Paramyxoviruses|Reptilian Paramyxoviruses]]
**Mumps
*'''Morbilliviruses'''
**[[Paramyxoviridae#Canine Distemper Virus (CDV)|Canine Distemper (CDV)]]
**Rinderpest
**Pest de petit ruminant (PPR)
**Measels
**Seal virus - phocine distemper
**Dolphin Morbillivirus
**[[Paramyxoviridae#Hendra Virus|Hendra virus]]
**[[Paramyxoviridae#Nipah Virus|Nipah virus]]
*'''Pneumovirinae'''
**[[Paramyxoviridae#Bovine Respiratory Syncytial Virus (BRSV)|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 ([[Paramyxoviridae#Canine Distemper Virus (CDV)|Distemper]], [[Paramyxoviridae#Newcastle Disease Virus (NDV)|NDV]])
*Links to the readiness to cleave Fo and Ho precursors in different cells
 
====Antigenic differentiation====
 
*Major conserved immunodominant virus-specific antigens on [[Paramyxoviridae#Structure|F and HN]]
**-> Vaccines protect against all isolates of the same virus
*Minor morbillivirus-specific epitopes on [[Paramyxoviridae#Structure|F]]
**Some crossprotectin between [[Paramyxoviridae#Canine Distemper Virus (CDV)|canine distemper]], measels and rinderpest
*Minor variable epitopes of [[Paramyxoviridae#Structure|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 Viral Infections - Pathology|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 [[Orthomyxoviridae|avian influenza]]
**Animal test: virulence of isolate tested by the speed it kills chicks
**Sequencing the cleavage site of [[Paramyxoviridae#Structure|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 [[General Pathology - Antigen Recognition, Processing and Presentation#NK Receptors|NK cells]] via high circulating [[Innate Immunity - Anatomy & Physiology#Interferons|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, [[Nasal cavity - inflammatory#Infectious causes of rhinitis|rhinitis]]
**Virus shed for a short time only
*Also part of kennel cough ([[Respiratory Viral Infections - Pathology#Infectious canine tracheitis|Infectious canine tracheitis]]), together with [[Bordetella bronchiseptica and Bordetella avium|''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 [[Respiratory System General Introduction - Pathology#Mucociliary escalator|ciliary clearance]] and epithelial necrosis predisposes to secondary bacterial infections -> cough
*May cause [[Respiratory Viral Infections - Pathology#Parainfluenza- 3|rhinitis]] of cattle
*With other agents causes [[Respiratory Bacterial Infections - Pathology#Enzootic pneumonia of calves|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<sup>o</sup>C but not at 37<sup>o</sup>C
***Re-infection is common
 
 
===Bovine Respiratory Syncytial Virus (BRSV)===
 
*'''Pathogenesis''':
**More serious than [[Paramyxoviridae#Parainfluenza -3 (PI-3)|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 [[Lungs - ventilation#Emphysema|emphysema]] and [[Lungs - circulatory#Pulmonary oedema|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 [[Paramyxoviridae#Parainfluenza -3 (PI-3)|PI-3]]
*'''Control'''
**Improve husbansry as in [[Paramyxoviridae#Parainfluenza -3 (PI-3)|PI-3]]
**Vaccines are available but not effective as need to stimulate [[Lymphocytes - Anatomy & Physiology#Cytotoxic CD8+|cytotoxic T-cells]]
*<small>'''Reference''': Bryson, 1999, Update on calf pneumonia, CPD Veterinary Medicine, 1,3, 90-95</small>
 
===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 - Anatomy & Physiology|macrophages]] or [[Oral Cavity - Oropharynx|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 Viral Infections - Pathology#Canine distemper|Respiratory]] and alimentary tracts, skin and later (1-5 wk. post infection) to the brain
*'''Clinical signs''':
**Mucopurulent oculonasal discharge
**Keratitis
**[[Lungs - inflammatory#Interstitial pneumonia|Interstitial pneumonia]]
**Severe clinical pneumonia follows secondary infection with [[Bordetella bronchiseptica and Bordetella avium|''Bordetella bronchiseptica'']]
**Smelly sometimes bloody diarrhoea
**Eruptions on the skin including hyperkeratosis of the nose and pads (hardpad)
**[[PNS Repsonses to Injury#Segmental Demyelination|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 [[Respiratory Viral Infections - Pathology#In Dogs|Infectious canine tracheitis]]
*May be involved in [[Pancreas - inflammatory#Chronic interstitial pancreatitis|chronic interstitial pancreatitis]]
*May cause [[Bones - developmental#Retention of elongated primary trabeculae|growth retardation lattice]]
*May also trigger latent [[Tissue cyst-forming coccidia|Toxoplasmosis]] due to suppressing effect on lymphoid tissue
 
===Hendra Virus===
 
*Equine Paramyxovirus
*Causes [[Respiratory Viral Infections - Pathology#Hendra virus|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
 
 
 
 
 
<big><center>[[Viruses|'''BACK TO VIRUSES''']]</center></big>

Revision as of 16:48, 31 July 2008

BACK TO VIRUSES


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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