JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2023

P-V24

 

Signalment (JPC #2156896): Tissue from a sheep.

 

HISTORY: None.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Approximately 30% of the section is characterized by multifocal nodules of consolidation up to 2mm in diameter centered on bronchioles (pocks). In these nodules, type I pneumocytes are replaced by markedly hyperplastic type II pneumocytes. In these areas, alveolar lumina are often filled with an exudate composed of eosinophilic fluid, hemorrhage, degenerate neutrophils, necrotic debris, lymphocytes, plasma cells, and moderate numbers of macrophages that have vesiculate nuclei and abundant amphophilic, foamy cytoplasm that contains one to multiple, round to oval, 2‑8µm diameter, pale eosinophilic, intracytoplasmic viral inclusion bodies (sheeppox cells). The bronchioles within the consolidated nodules are lined by hyperplastic epithelium that is piled up to five layers thick, that occasionally contains 2-4µm diameter eosinophilic intracytoplasmic viral inclusion bodies and few mitotic figures, and is transmigrated by degenerate neutrophils. Multifocally bronchiolar lumina contain a small amount of fibrinous exudate. The majority of the remaining alveolar septa are mildly expanded up to 4x normal by lymphocytes, macrophages, and neutrophils. Predominantly in areas of consolidation there is moderate expansion of the arterial and arteriolar and tunica intima and tunica adventitia by edema, fibrin, lymphocytes, and few necrotic neutrophils (vasculitis). Endothelial cells are multifocally hyperplastic (reactive).  

 

MORPHOLOGIC DIAGNOSIS: Lung: Alveolitis and bronchiolitis, proliferative, subacute, multifocal, moderate, with nodular type II pneumocyte hyperplasia, mild lymphohistiocytic interstitial pneumonia, intrahistiocytic eosinophilic intracytoplasmic viral inclusions (sheeppox cells), and intraepithelial eosinophilic intracytoplasmic viral inclusions, breed unspecified, ovine. 

 

ETIOLOGIC DIAGNOSIS: Capripoxviral pneumonia

 

CAUSE: Sheeppox virus (Capripoxvirus, ovine strain)

 

GENERAL: 

• Capripoxvirus (subfamily Chordopoxvirinae; family Poxviridae) – dsDNA virus with complex ovoid or brick shaped virons 
• Acute to chronic, contagious, systemic disease characterized by generalized pox lesions throughout the skin (especially sparsely wooled areas) and mucous membranes, persistent fever, lymphadenitis, and often pneumonia 
• Endemic in North Africa, Asia, and the Middle East; exotic to the Americas, Australia and New Zealand; OIE list A disease with expanding range and occasional epidemics
• Occurs in all ages, but most severe in young lambs, with high mortality (80‑100%, 50% in adults)  
• Fine‑wooled sheep (Merinos) are especially sensitive; breeds native to endemic areas are more resistant to infection (i.e. Algerian sheep)
• Extensive losses result from high mortality in lambs, abortions and mastitis in ewes, and skin defects (loss of milk, meat, and/or fiber yield); also costs of quarantine and disease prevention efforts
• The virus is resistant to desiccation and may remain viable in wool for 2 months or in dried crusts for up to 6 months

 

PATHOGENESIS:

• Sheeppox and goatpox are the most virulent of the pox diseases in domestic animals, and cause systemic illness
• Introduction of virus is predominately via the respiratory tract, but also through skin abrasions > local viral replication in epidermis, dermis, or oronasal pharynx (epitheliotropic) > regional lymph nodes via macrophages > replicates in cytoplasm of epithelial cells, mucosal lymphocytes and macrophages, and dendritic cells > exits via efferent lymphatics into blood > cell-associated viremia occurs causing extensive vasculitis in arterioles and post‑capillary venules (immune‑mediated complex deposition), thrombosis, and ischemic necrosis with intense infiltration of neutrophils; virus has not been identified in endothelial cells
• Stomoxys calcitrans (stable fly) is an efficient mechanical vector of capripox, though the role of mechanical vectors in spread of the disease is probably limited
• Sheeppox cells are CD14 and CD172a positive (antigens expressed on monocytes and macrophages)
• Pulmonary pock lesions mainly composed of hyperplastic type II pneumocytes and bronchiolar epithelial cells,  variable numbers of neutrophils/lymphocytes, extracellular eosinophilic fluid, and foci of caseous necrosis 

 

TYPICAL CLINICAL FINDINGS:

• Fever, seromucous oculonasal discharge, increased respiratory rate, eyelid edema, drooling, and hyperesthesia
• Vesicular stage: Generalized prominent, umbilicated, multilocular vesicles and cutaneous nodules (0.5‑1.5 cm in diameter) 
• Pustular phase: Coalescing vesicles covered by a thin crust  
• In animals that recover, the lesions ultimately heal, leaving permanent depressed scars (stellate on the skin)

 

TYPICAL GROSS FINDINGS:

• Most cutaneous lesions (vesicles, nodules, ulcerations, and crusts) are confined to sparsely wooled skin and mucous membranes (eyelids, cheeks, nostril, udder, etc), characterized by a prominent vesicular stage followed by a pustule stage with thin crusts and gelatinous dermal edema
• One-third of the animals develop respiratory lesions: disseminated random miliary to nodular white foci of consolidation due to hematogenous infection; there may be a concurrent tracheitis (hyperplastic nodules)  
• Renal lesions consist of multifocal, circular, fleshy nodules throughout cortex  

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Cutaneous lesions:  
  • Epidermis and follicular epithelium displays marked hydropic degeneration, marked vacuolar degeneration of stratum spinosum, microvesiculation, eosinophilic intracytoplasmic viral inclusion bodies (ICIB), epidermal hyperplasia (including stratum spinosum hyperplasia [acanthosis)], hemorrhage, and pustule formation 
  • Extensive dermal edema during the papular phase with accumulation of many mononuclear cells around blood vessels and between collagen bundles; these cells (sheeppox cells, cellules claveleuses of Borrel) have vacuolated cytoplasm with eosinophilic ICIB and vacuolated nuclei with marginated chromatin
  • Sheeppox cells are virus-infected monocytes, macrophages, and fibroblasts, but not endothelial or epithelial cells
  • Severe necrotizing vasculitis develops in arterioles and post-capillary venules resulting in dermal and epidermal ischemic necrosis 
• Respiratory lesions:
  • Lung: proliferation of virus-containing bronchiolar epithelium and type II pneumocytes (proliferative alveolitis and bronchiolitis) with areas of focal caseous necrosis with infiltration of sheeppox cells, neutrophils, and lymphocytes, and formation of gland-like structures; alveolar septal and bronchiolar epithelial cells may contain ICIB 
  • Trachea: May cause hyperplastic nodules in the trachea
• Additional lesions:
  • Accumulation of sheeppox cells may occur in heart, kidney, adrenal glands, thyroid gland, and pancreas; may see necrosis and lymphoid depletion in lymphoid organs

 

ULTRASTRCTURAL FINDINGS:  

• Intracytoplasmic oval (brick shaped) virions measuring 220-300 X 140-170nm in keratinocytes and macrophages
• Infected cell nuclei often have marginated chromatin and a central, less electron dense area with fine filaments arranged singly or in bundles

 

ADDITIONAL DIAGNOSTIC TESTS:

• Virus isolation from enlarged lymph nodes; Virus neutralization; Indirect fluorescent antibody
• PCR

 

DIFFERENTIAL DIAGNOSIS:

Respiratory Lesions:

• Ovine Pulmonary Adenocarcinoma (P-V16, Betaretrovirus): Multifocal well-differentiated pulmonary carcinoma
• Ovine Progressive Pneumonia (P-V17, Lentivirus; Retroviridae): Mononuclear interstitial pneumonia, BALT hyperplasia, smooth muscle hyperplasia, minimal type II pneumocyte hyperplasia; no intraalveolar inflammation; no viral inclusions
• Parainfluenza type 3 (Paramyxovirus): Bronchointerstitial pneumonia with eosinophilic ICIB and occasional syncitial cells

Cutaneous Lesions:

• Foot and Mouth Disease (D-V17, Aphthovirus; Picornavirus): Vesicles on feet and mucosa of dental pad
• Contagious ecthyma (I-V11, Orf virus, Parapoxvirus): Lesions muzzle, eyelids, and teats; most severe in lambs and kids zoonotic 
• Bluetongue (D-V16, M-V01, N-V02; Orbivirus; Reoviridae): Nonpurulent conjunctivitis; congested and edematous muzzle; coronitis; deformed aborted fetuses
• Peste des Petits Ruminants (P-V04, Morbillivirus; Paramyxoviridae): White, raised, necrotic oral lesions; pneumonia and diarrhea

 

COMPARATIVE PATHOLOGY:

Selected other poxviruses:

• Capripoxvirus: 

• Goats: Goatpox - clinically similar disease, but is usually milder 
• Cattle: lumpy skin disease (reportable) - ulcers in mouth, nares; circumscribed lesions in lungs and alimentary tract; Jersey and Guernsey most susceptible

• Orthopoxvirus: Camelpox, Cowpox, Ectromelia (mousepox), Monkeypox, Vaccinia (buffalopox, rabbitpox), Uasin Gishu disease virus, Elephant pox
• Parapoxvirus: Bovine popular stomatitis, Orf, Parapox of red deer, Squirrel pox, Pseudocowpox, Sealpox, Camel and chamois contagious ecthyma
• Avipox: Fowlpox, Pigeonpox
• Leporipox: Myxomatosis, Rabbit (Shope) fibroma, squirrel fibroma virus
• Suipox: Swinepox
• Molluscipox: Molluscum contagiosum
• Yatapox: Tanapox, Yaba monkey tumor
• Cetacean poxvirus:  forms a unique tattoo pattern on skin; has characteristics of both parapox and orthopoxviruses via TEM and SEM
• Crocodile poxvirus

 

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