JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2023

P-V07

 

Signalment (JPC #2237801): Adult female king snake

 

HISTORY: This is one of six snakes in a private collection of over 250 snakes that developed vomiting and runny yellow feces over a period of 6 months. Three snakes died.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Diffusely faveolar septa are markedly expanded up to 100 microns by edema, fibrin, congestion, and low numbers of macrophages, lymphocytes, and heterophils. Faveolar lumina are multifocally to diffusely lined by hyperplastic cuboidal epithelial cells (type II pneumocyte hyperplasia). Pneumocytes are often swollen and vacuolated (degenerate) or rarely shrunken with a hypereosinophilic cytoplasm and a pyknotic or karyorrhectic nucleus (necrotic). Multifocally, pneumocytes form approximately 30 µm diameter syncytial cells with up to 10 nuclei. Pneumocytes and syncytial cells contain variably shaped, 3-5 µm, eosinophilic intracytoplasmic viral inclusion bodies. Multifocally, faveolar lumina contain an exudate composed of degenerate heterophils, occasional macrophages, fibrin, sloughed epithelial cells, and abundant necrotic cellular and karyorrhectic debris. The respiratory epithelium lining the septal apices and central lumen is diffusely hyperplastic, piling up to 7 cell layers thick, and these epithelial cells are often swollen and vacuolated (degenerate) and contain similar intracytoplasmic inclusions. The pleura is diffusely expanded up to 1 mm by edema, congested blood vessels, low numbers of lymphocytes, plasma cells, macrophages, and heterophils.  

  

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, interstitial, proliferative and lymphohistiocytic, diffuse, moderate, with type II pneumocyte hyperplasia, syncytial cells, and intracytoplasmic eosinophilic inclusion bodies, King Snake (Lampropeltis spp.), reptile.

 

ETIOLOGY: Ferlavirus

 

ETIOLOGIC DIAGNOSIS: Ferlaviral pneumonia

 

SYNONYMS: Ophidian (snake) paramyxovirus (OPMV), Viper pneumonitis virus, Fer-de-lance virus

 

GENERAL DISCUSSION:   

• Single-stranded enveloped pleomorphic RNA virus; Family Paramyxoviridae; genus Ferlavirus 
• Causes respiratory, central nervous system, and pancreatic disease in snakes
• Reported most commonly in captive viperids and crotalids, but colubrids, elapids, and boids are also susceptible
• Can also infect lizards and tortoises, but rarely causes disease
• Secondary gram-negative bacterial infections are common sequelae

 

PATHOGENESIS: 

• Inhalation of contaminated respiratory secretions > virions bind and fuse to respiratory epithelium via two glycoproteins located on their envelopes:  
  • Hemagglutinin-neuraminidase (HN) protein - Hemagglutinin is an attachment protein and neuraminidase mediates virion release by cleaving receptor attachments
  • Fusion (F) protein - Mediates fusion of the viral envelope with the cellular membrane, assists in viral attachment, and mediates syncytia formation
• Virions enter epithelial cells > transcription of viral progeny > infected cells undergo virus-induced lysis > desquamate from the mucosa >  secondary bacterial infection
• Syncytia allow for spread without virus release in the presence of antibodies

 

TYPICAL CLINICAL FINDINGS:

• Nasal discharge
• Caseous debris in oral cavity 
• Gaping of the mouth with abundant clear mucus 
• Prostration and loss of muscle tone (appearing “stretched out”), head tremors  
• Expulsion of brown bloody fluid from the glottis or regurgitation of previously eaten prey  
• May die within 24 hrs of initial signs; often found dead   

 

TYPICAL GROSS FINDINGS:   

• Respiratory tract is the primary target of Paramyxovirus in snakes  
• Lungs are thickened, edematous, and congested
• Hemorrhage and/or mucoid or caseous necrotic exudate within the airways 
• Blood may be found in the coelomic cavity or mouth   
• Terminally, many snakes expel a caseopurulent material (due to secondary bacterial infection) from the glottis which may fill the nasal passages, cover the oral mucosa, and may be swallowed into the upper esophagus
• Pancreatic inflammation and necrosis, and encephalitis are also reported 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Proliferative interstitial pneumonia with prominent type II pneumocyte hyperplasia and variable lymphocytic interstitial inflammation 
• Epithelial syncytia and eosinophilic intracytoplasmic inclusion bodies within pneumocytes together are diagnostic features of OPMVs      
• Variable degeneration, necrosis, hypertrophy, and hyperplasia of airway epithelium +/- alveolar exudate composed of desquamated epithelial cells, heterophils, and erythrocytes 
• Secondary gram-negative bacterial infections are a common sequela and often spread to the liver, kidneys, and the female reproductive system 
• Pancreas - pancreatic ductular hyperplasia and acinar necrosis with heterophilic and lymphocytic infiltrates
• Liver - diffuse hepatic necrosis or multifocal pyogranulomatous inflammation with eosinophilic intracytoplasmic inclusions
• Nervous system – meningoencephalitis with demyelination, lymphocytic perivascular cuffing, neuronal degeneration +/- neuronal intranuclear and glial intracytoplasmic viral inclusion bodies

 

ULTRASTRUCTURAL FINDINGS:  

• Aggregates of 12-18 nm ribonucleic-like tubular particles (“herringbone” nucleocapsid material)
• Budding virions from epithelial cell plasma membrane   

 

ADDITIONAL DIAGNOSTIC TESTS: 

 

DIFFERENTIAL DIAGNOSIS:

• Aspiration pneumonia
• Viral 
  • Nidovirus – Causes segmental esophagitis in addition to epithelial syncytia and intracytoplasmic viral inclusions
  • Sunshine coast virus (family Sunviridae, order Mononegavirales) – Neurorespiratory disease of Australian pythons that causes spongiosis and gliosis of the hindbrain white matter +/- mild bronchointerstitial pneumonia with syncytia
  • Reovirus – Causes mild proliferative pneumonia and tracheitis, but syncytia, viral inclusions, and hemorrhage are not reported
  • Adenovirus – Large, basophilic intranuclear inclusion bodies
  • Boid Inclusion Body Disease (Arenavirus) – Eosinophilic intracytoplasmic inclusion bodies with lack of associated inflammation
• Bacterial
  • Pasteurella multocida, P. hemolytica, P. testudinis – pyogranulomatous interstitial pneumonia
  • Pseudomonas and Aeromonas spp.
  • Edwardsiella tarda, Klebsiella and Proteus spp.
  • Staphylococcus aureus and hemolytic Streptococcus spp.
  • Salmonella spp.
  • Escherichia coli  
  • Mycobacterium spp. – in acute cases, suppurative pneumonia; in chronic cases, granulomatous pneumonia
• Fungal 
  • Aspergillus
  • Candida spp.
• Parasitic 

• Severe lungworm (Rhabdias spp.) infestation
• Severe pentastome infestation

 

COMPARATIVE PATHOLOGY:

Family Paramyxoviridae (7 genuses)

• Genus Ferlavirus:
  • Fer-de-Lance virus and all other identified reptile/ophidian paramyxoviruses (OPMVs) 
  • Paramyxovirus-associated disease in lizards has only been reported in Caiman lizards and a water dragon
    • Gross lesions - yellow/gray mucoid fluid and flocculent material in the central airway of the lungs
    • Microscopic lesion - proliferative heterophilic and histiocytic interstitial pneumonia with type II pneumocyte hyperplasia, syncytia, and intracytoplasmic eosinophilic inclusions 
• Genus Aquaparamyxovirus (salmon paramyxoviruses)
• Genus Avulavirus
  • Newcastle Disease (Avian paramyxovirus 1) 
  • Avian paramyxoviruses (types 2-9) 
• Genus Henipavirus
  • Hendra virus
  • Nipah virus
• Genus Morbillivirus
  • Rinderpest
  • Pests de petits ruminants virus
  • Canine distemper virus
  • Marine morbillivirus
  • Feline morbillivirus
  • Measles virus
• Genus Respirovirus:
  • Sendai virus (Murine parainfluenza -1)
  • Bovine parainfluenza -3 
• Genus Rubulavirus:
  • Canine parainfluenza virus 5 (Simian virus 5)
  • Porcine rubulavirus 
  • Manangle virus

 

References:

 

 

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