Respiratory Viral Infections

()Map CARDIORESPIRATORY SYSTEM (Map) RESPIRATORY SYSTEM INFLAMMATION

In general

• Some viruses are thought to induce modifications of the pulmonary defences by:
  • Damaging the upper respiratory tract, thereby facilitating bacterial attachment and colonisation, with reduced mucociliary clearance
  • Decreasing surfactant levels by destroying Type 2 pneuMonocytes - WikiBlood
  • Impairing the phagocytic ability of alveolar macrophages

In Dogs

Canine distemper

• Caused by a morbillivirus
• Rhinitis
• Although many organs can be affected by CDV, a relatively constant feature is the respiratory signs which occur in varying severity
• A syndrome of catharral oculonasal discharge, pharyngitis and bronchitis is relatively common in the initial stages
• Since one of the primary sites of action of this virus is lymphoid tissue, the resultant immunosuppression -> predisposition to secondary bacterial infection
• May cause interstitial pneumonia where inclusions are found within alveolar macrophages
• Gross pathology:
  • Oedematous lungs, diffuse interstitial pneumonia
• Micro pathology:
  • Necrosis of pneumocytes, necrotising bronchiolitis, alveolar oedema, thickening of alveolar walls and type II pneumocyte hyperplasia

Parainfluenza- 2

• Caused by an parainfluenza- 2 virus
• Rhinitis, tracheobronchitis

Infectious canine tracheitis

• Synonyms: Kennel cough, Infectious tracheobronchitis
• tracheitis, bronchitis
• Multiple agents implicated:
  • Canine adenovirus-2
  • Canine parainfluenza-2 virus
  • Canine distemper virus
  • Bordetella bronchoseptica
• Symptoms are of a persistent, non-productive cough
• Persistent tracheobronchial inflammation
• The outcomes is generally recovery (may persist >3 weeks), but extension to chronic bronchitis or cranioventral bronchopneumonia may occur
• In severe cases can extend to serous/mucopurulent rhinitis
• Lesions are neither specific nor always significant (catarrhal / mucopurulent tracheobronchitis)
• Enlarged tonsils and retropharyngeal lymph nodes

Canine adenovirus

Adenovirus pneumonia (Image sourced from Bristol Biomed Image Archive with permission)

• Adenoviridae
• Usually mild bronchointerstitial pneumonia, necrosis of bronchiolar and alveolar epithelium, oedema, type II pneumocyte hyperplasia
• May cause necrotising bronchiolitis in immune-deficient dogs (distemper)
• Can be associated with kennel cough described above

Canine herpes virus

• Caused by canine herpes virus 1
• Part of fading puppy syndrome
• Presents with necrotising rhinotracheitis and secondary bronchopneumonia in older dogs
• Seems to be common subclinically

Canine respiratory coronavirus

• (CRCV)
• Shown to be involved in an outbreak of disease in large kennels with rapidly changing population and high incidence of respiratory disease
• Erles, K., Toomey, C. et al.(2003) "Detection of a group 2 coronavirus in dogs with canine infectious respiratory disease." Virology 310(2):216-223

In Cats

Feline viral rhinotracheitis

• Caused by a herpesvirus
• Tends to be more rhinitis than tracheitis, may extend to sinusitis
• Feline herpesvirus -1
  • One of the causes of Feline viral rhinotracheitis
    • Viruses and bacteria are involved in the complex. The most frequent aetiologic agent is FHV-1, and less frequently feline calicivirus and/or Chlamydophila psittaci (NB: previously called Chlamydia psittaci var felis)
• All three agents infect URT respiratory epithelium, although FHV-1 has the highest affinity for this epithelium
• Feline calicivirus more frequently infects the oral mucosa -> ulcerative stomatitis
• C.psittaci more frequently infects the conjunctival epithelium -> chronic conjunctivitis
• Infection of the respiratory epithelium by FHV-1 results in a typical neutrophilic rhinitis with intraepitheial intranuclear eosinophilic inclusion bodies
• Uncomplicated cases resolve in 2-3 weeks
• FHV-1 remains latent in the trigeminal ganglion, and can reactivate at times of stress
• Can infect the cornea -> ulcerative keratitis
• Mortality may be high in young kittens, debilitated and immune-suppressed animals, usually associated with secondary bacterial infection.

Feline calicivirus

• Causative agent: feline calicivirus
• Rhinitis,
• Suggested in the presence of ulceration of the dorsal and lateral edges of the tongue, hard palate and external nares
• Lesions present may include interstitial pneumonia with necrotising bronchiolitis
• Also see Feline viral rhinotracheitis above

In Horses

Equine respiratory viruses Concept Map (Courtesy of B. Stanikova)

Equine rhinovirus

• Causative agent: equine rhinovirus
• Rhinitis
• Most common in young horses
• May cause acute upper respiratory disease

Equine influenza

• Causative agent: equine influenza virus (Orthomyxovirus)
• Rhinitis,
• Pathogenesis:
  • Inhalation -> replication in epithelial cells of upper and lower airways (attaches via haemaglutinin spike and gains entry into cell) -> neuramidase alters efficiency of mucociliary apparatus
• Sloughing of the affected area
• Severity of signs will depend on dose of virus
• Acute tracheobronchitis with coughing, and fever
• May be accompanied by secondary bacterial infections
• No viraemia
• In severe cases may cause bronchointerstitial pneumonia
• Secondary invaders are usually Streptococci

Equine rhinopneumonitis

• Causative agent: equine herpesvirus type 1 and type 4
• Primary viral lesions in nasal mucosa and lungs
• Mild, transient bronchointerstitial pneumonia
• Latent infection acting as a reservoir
• Sites of latency: bronchial lymph nodes and trigeminal ganglia
• Replicates in upper respiratory tract epithelium
• Disseminated to lower respiratory tract
• Transported to other organs in T-lymphocytes - viraemia up to 3 weeks
• Vasculitis, abortion
• May be accompanied by secondary bacterial infection

Equine viral arteritis (EVA)

• Causative agent: equine arterivirus
• Rhinitis, peripheral oedema, bronchitis/bronchiolitis, conjunctivitis, periorbital oedema
• Replicates in macrophages and endothelial cells
• Disseminates via the circulatory system causing necrotising arteritis
• Interstitial pneumonia
• Transmitted by respiratory and venereal routes through direct contact with infected horse or its secretions
• Stallion are a reservoir of infection as they are chronic shedders

Equine adenovirus

Adenovirus in equine lung (Image sourced from Bristol Biomed Image Archive with permission)

• Adenoviridae
• May cause necrotising bronchiolitis in immune-deficient foals (Arabian foals)
• Grossly:
  • Atelectasis and consolidation of lobules in cranioventral region
  • Mucopurulent exudate in airways
• Histologically:
  • Severe bronchiolitis, necrotising -> proliferative
  • Bronchiolar obstruction by sloughed debri and neutrophils -> alveolar atelectasis
• May lead to secondary bacterial infections

African horse sickness

Lung oedema in African horse sickness (Image sourced from Bristol Biomed Image Archive with permission)

• Caused by orbivirus, family reoviridae
• Respiratory distress or cardiovascular failure
• Rapid death due to massive pulmonary oedema
• Hydrothorax may also develop
• Large amounts of froth present in airways

Hendra virus

• Causative agent equine morbillivirus
• Oedematous lungs with distention of pleura
• Micro: diffuse alveolar oedema, syncytial cells

In Cattle

Infectious bovine rhinotracheitis (IBR)

IBR in nasal cavity (Image sourced from Bristol Biomed Image Archive with permission)

IBR in trachea (Image sourced from Bristol Biomed Image Archive with permission)

• Causative agent is bovine herpesvirus, type 1
• URT infection with serous nasal discharge, increases respiratory rate, coughing and moderate fever,from nasal mucosa down to bronchioles
• Rhinitis, pharyngitis, laryngitis, tracheitis, bronchiolitis
• Morbidity is high, mortality is low
• Highly infectious URT disease of cattle
• Spread by movement of animals, aerosol transmission - requires close contact between animals
• Early stages (only first few days) may show intracellular inclusions in the respiratory mucosal epithelial cells
• Leading to neutrophilic inflammation of varying severity.... serous -> catarrhal -> purulent
• With secondary bacterial infection (eg: Pasturella spp., Mycoplasma spp., Fusobacterium necrophorum) can lead to fibrinous to necrotizing inflammation; mucosal sloughing, ulceration... pyrexia, dyspnoea ... inhalation pneumonia... death
• Underlying hyperaemic inflammatory response
• Can become latent following primary infection
• Clinical signs:nasal discharge, sneezing, coughing, lacrimation, and increased respiratory rate
• Clinical disease most severe in young calves - can develop mucosal ulcerative lesions in the oesophagus and forestomachs and viraemia with multiorgan infection
• Cause of abortion >5 months of gestation
• May contribute to Enzootic pneumonia of calves

Parainfluenza- 3

• Causative agent: parainfluenza- 3 virus (PI3)
• On its own causes rhinitis
• Often part of multi-aetiology disease complex (e.g. Enzootic pneumonia of calves), often followed by Pasteurella sp. obscuring viral origin
• Replicates in airway epithelial cells and results in an initial bronchitis -> bronchiolitis -> extension into alveoli, causing bronchointerstitial pneumonia
• Early stages may show intracytoplasmic inclusions
• The resulting exudate is predominantly neutrophilic
• Positive confirmation lies in a Fluorescent Antibody Test (FAT) to the specific virus on frozen sections of tissue

Bovine adenovirus

• Causative agent: bovine adenovirus
• Rhinitis
• May contribute to Enzootic pneumonia of calves

Respiratory syncytial virus

• Causative agent Respiratory syncytial virus (RSV), synonym: bovine RSV (BRSV)
• Outbreaks of RSV associated disease usually occur associated with winter housing
• Gross pathology in severe cases
  • Cranioventral atelectasis and consolidation
  • Interstitial emphysema
    • More prominent in the caudal lung lobes
    • Results from bronchoconstriction which results in airway obstruction - this constriction is thought to arise from mast cell degranulation and histamine release
• Histologically
  • Acute bronchiolitis, characteristic of the bronchiolar response is the formation of syncytial giant cells (formed by proliferating bronchiolar epithelial cells which may contain intracytoplasmic inclusion bodies), alveolar epithelium sometimes affected
  • Obstruction of bronchioles by exudate - these may later become obliterated by the fibrous tissue of organisation
• May contribute to Enzootic pneumonia of calves

Bovine rhinovirus

• Causative agent: bovine rhinovirus
• May cause mild respiratory disease

In Sheep

Maedi Visna

• Caused by a retrovirus
• The respiratory from of the disease caused by maedi-visna virus (Maedi) is also called lymphoid interstitial pneumonia
• Transmitted by close contact and via milk
• The pulmonary lesions develop very slowly hence this disease is uncommon in sheep < 2 years old
• Increased respiratory rate upon exertion, loss of weight
• Remains in Monocytes - WikiBlood and macrophages
• Gross findings
  • Severe interstitial pneumonia
  • Lungs fail to collapse properly on opening the chest and can weigh more than twice the normal weight
  • Impressions of the ribs remain on the visceral pleura
  • Lungs are a mottled grey/ tan colour - the lesions can vary from irregular grey speckling to homogeneous grey consolidation
  • Rubbery in consistence
  • Diaphragmatic lobes most affected
  • Associated bronchial and mediastinal lymph nodes are often enlarged
• Histologically
  • Major features are extensive lymphoid proliferation around perivascular, peribronchial and peribronchiolar sheaths associated with pulmonary lymphatics
  • Many of these areas contain germinal centres and smooth muscle hyperplasia (in walls of terminal bronchioles and alveoli)

Parainfluenza -3

• As in cattle

Pulmonary adenomatosis

• See neoplasia

In Goats

Caprine Arthritis-Encephalitis (CAE)

• Caused by retrovirus (lentivirus) similar to Maedi Visna in sheep described above
• Two forms:
  • Non-suppurative leukoencephalomyelitis in young goats and kids
  • Chronic, non-suppurative arthritis-synovitis in adult goats
• Also causes interstitial pneumonia which tends to be obscured by other clinical signs
• Gross pathology:
  • Mainly caudal lobes
  • Lungs are firm, grey-pink with grey-white focal lesions on cut surface
• Micro pathology:
  • Thickened alveolar wall
  • Lymphocyte infiltration and type II pneumocyte hyperplasia
• Can be confused with or coexisting with Parasitic pneumonia

In Pigs

Inclusion body rhinitis

Inclusion body rhinitis (Image sourced from Bristol Biomed Image Archive with permission)

• Herpesviridae, porcine cytomegalovirus
• Disease of suckling piglets 1-5 wks of age
• Clinical signs: those associated with acute/subacute rhinitis (ie: serous nasal discharge, progressing to catarrhal or purulent discharge with time and secondary bacterial infections; sneezing; pyrexia), fever in young piglets (3-8wks old)
• May progress to sinusitis, otitis media or pneumonia
• Morbitity high, mortality low
• Gross pathology - catarrhal discharge becoming purulent (secondary infection)
• Histology:
  • Large basophilic intranuclear inclusion bodies in the surface and subepithelium of nasal and sinus glandular epithelium with lymphocytic infiltration of the mucosa
  • Bursting of nucleus with cell necrosis and sloughing of necrotic epithelium
• Can develop viraemic stage, with inclusions and focal necrotising lesions in other organs eg: renal tubular epithelium
  • Usually younger piglets, can die during this phase
• Usually resolves if uncomplicated but rhinitis may persist if secondary infection is present
• May persist in pulmonary macrophages

Swine influenza

• Caused by Swine influenza virus
• Rhinitis, may progress to pneumonia
• Clinical signs: pyrexia, lethargy, skin erythema, anorexia, severe cough and sneezing, dyspnoea, conjunctivitis, pregnant sows may abort
• Grossly:
  • Tracheobronchitis, airway obstruction -> atelectasis
  • Pleura normal or covered with serous or serofibrinous exudate
  • Pleural cavity filled with excess fluid
  • Lung lesions
    • Clear demarcation of lesions in cranial and middle lobes
    • Interstitial pneumonia
• Histologically:
  • Acute inflammation of mucosa of trachea and bronchi
• Zoonotic
• Circumstantial evidence of mutation from human strain
• Migrating ascarids thought to precipitate the disease, reservoir of infection in earthworms containing infected lungworm larvae

Porcine reproductive and respiratory syndrome

• The syndrome is caused by a small enveloped RNA virus which belongs to the new Arteriviridae group
• Replicates in and destroys macrophages and endothelial cells causing vasculitis -> viraemia -> virus shedding (nasal secretions, faeces)
• Clinical signs: respiratory and reproductive failure, weaned pigs, tachypnoea, eyelid oedema, conjunctivitis
• Moderate to severe interstitial pneumonia in the cranial lobe
• Superimposed bacterial infections are common
• Infectious disease in swine that emerged 10 years ago
• Today, PRRS is endemic in many if not all the pig-producing countries

Postweaning multisystemic wasting syndrome (PMWS)

• Caused by a porcine circovirus alone or in combination with porcine parvovirus
• May cause mild interstitial pneumonia, failure of lungs to collpse on opening the thoracic cavity
• Microscopically: thickening of alveolar wall due to type 2 pneumocyte hyperplasia

Porcine respiratory coronavirus (PRCV)

• Caused by a coronavirus
• Usually mild pneumonia unless complicated by other agents
• Virus replicates in epithelial lining of airways