JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2023

P-V17

 

Signalment (JPC #2127420): 2‑year‑old ewe

 

HISTORY: This ewe had sustained severe weight loss over the winter while receiving a ration adequate for maintenance.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Alveolar septa are diffusely expanded up to eight times normal by a cellular infiltrate composed of lymphocytes, macrophages, and neutrophils admixed with minimal fibrous connective tissue (fibrosis) and small amounts of fibrin and edema. Multifocally, there is an increased amount of bronchiolar and alveolar smooth muscle (smooth muscle hypertrophy and metaplasia). Multifocally, the peribronchiolar and perivascular connective tissue is expanded by a similar inflammatory infiltrate, increased clear space and dilated lymphatics (edema), and numerous variably-sized aggregates of lymphocytes forming lymphoid follicles with germinal centers (BALT hyperplasia). Multifocally, bronchial and bronchiolar lumina occasionally contain amphophilic fibrillar to flocculent material (mucin) that is admixed with sloughed epithelial cells, cellular and karyorrhectic (necrotic) debris, and/or pale eosinophilic homogenous (seroproteinaceous) fluid, fibrin, and small amounts of hemorrhage.  

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, interstitial, lymphohistiocytic, chronic, diffuse, marked, with bronchus-associated lymphoid hyperplasia and bronchiolar smooth muscle hypertrophy, breed unspecified, ovine.

 

ETIOLOGIC DIAGNOSIS: Lentiviral pneumonia

 

CONDITION: Ovine progressive pneumonia (OPP); Maedi

 

CAUSE: Small ruminant lentivirus

 

Signalment (JPC #2127420): 2-year-old LaMancha goat

 

HISTORY: This LaMancha goat had severe weight loss and clinical signs of respiratory disease.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Multifocally, 70% of bronchioles and blood vessels are surrounded by large aggregates of inflammatory cells composed predominantly of lymphocytes and macrophages with fewer plasma cells that form lymphoid follicles with prominent germinal centers (BALT hyperplasia). Diffusely alveolar septa are expanded to up to 50 µm by lymphocytes, macrophages, fewer plasma cells, and fibrosis, and they are often lined by plump, cuboidal pneumocytes (type II pneumocyte hyperplasia). Alveolar lumina are filled with abundant eosinophilic proteinaceous fluid (surfactant and edema), mucin, foamy alveolar macrophages, few neutrophils, cellular debris, and occasional small areas of hemorrhage and mineral.  Bronchial and bronchiolar lumina multifocally contain edema and mucin admixed with degenerate and viable neutrophils and sloughed epithelium. Multifocally, the interlobular septa and pleura are expanded up to two times normal by ectatic lymphatics (edema), moderate amounts of fibrin, low numbers of lymphocytes, macrophages, rare eosinophils, occasional mineral, and a focally extensive area of mild hemorrhage.  

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, interstitial, lymphohistiocytic, chronic, diffuse, severe, with bronchus-associated lymphoid hyperplasia, type II pneumocyte hyperplasia, and abundant pulmonary edema, LaMancha, caprine.

 

ETIOLOGIC DIAGNOSIS: Lentiviral pneumonia

 

CAUSE: Small ruminant lentivirus (caprine arthritis encephalitis virus [CAEV])

 

SYNONYMS: Lymphoid interstitial pneumonia, maedi-visna (MVV), Graaff-Reinet (South Africa), Zwoegerziekte (Netherlands) and La bouhite (France) 

 

GENERAL DISCUSSION: 

• Small ruminant lentiviruses (SRLV) are closely related/overlapping non-oncogenic, single-stranded, enveloped, RNA virus in the family Retroviridae 
• Cause lifelong, persistent viral infection with varying disease severity in sheep and goats
• Multiple syndromes: Slowly progressive interstitial pneumonia, encephalitis, arthritis, and mastitis; syndromes may occur independently or concurrently; presentations influenced by breed, genetics, and tissue microenvironments
• Sheep: Maedi-Visna

• Respiratory form (ovine progressive pneumonia) is the most common; occurs in sheep > 3 years old; known as maedi (dyspnea) in Icelandic
• Encephalitis (N-V13) occurs in sheep > 2 years old; known as visna (fading away/neurologic form) in Icelandic 
• Encephalitis, arthritis, and mastitis are uncommon presentations in sheep

• Goats: Caprine arthritis encephalitis

• Neurologic disease (nonsuppurative leukoencephalomyelitis, N-V13) in kids and young goats (<4 months)
• Arthritis (chronic nonsuppurative, M-V02) in adults; may be the only manifestation of infection in a herd

• Pneumonia in adults or kids

 

PATHOGENESIS:

     (1) gag encodes nucleocapsid and matrix glycoproteins, basis of antibody test

     (2) pol encodes reverse transcriptase and other enzymes  

      (3) env encodes surface glycoproteins which mediate receptor binding and entry; target for neutralizing antibody

     (4) vif, rev, and vpr-like encode regulatory proteins

• Transmission: Virus may be free or cell-associated (macrophages); colostrum or milk (most common); inhalation of nasal secretions following prolonged close contact; in utero (infrequent)
• Virus infects alveolar macrophages or mucosal dendritic cells à lymph nodes à enters macrophages via mannose receptor à systemic spread
• Replication is restricted in most cells and occurs only in mature macrophages after cytokine-dependent activation; requires integration of provirus into the host genome; Kupffer cells in liver not permissive
• Infection of monocyte-precursors in bone marrow à infected monocytes migrate and mature into tissue macrophages à cytokine-dependent activation of mature macrophages à viral replication in macrophages à infected macrophages secrete high concentrations of IL-8; recruited inflammatory cells also secrete variety of cytokines (particularly from cytotoxic T cells) that result in chronic inflammation à interstitial pneumonia
• Incubation > 2 years; disease develops slowly
• Infection and shedding are life-long
• Immunosuppression is NOT a feature of small ruminant lentiviral infection (compared to other lentiviruses in primates and cats)

 

TYPICAL CLINICAL FINDINGS:

• Slowly progressive disease with emaciation and death
• Pneumonia: Dyspnea (especially during exertion)
• Arthritis and synovitis: Lameness with swollen joints (“big knee”), mostly in adults (especially carpal and tarsal joints)
• Mastitis: Hard, indurated udder and reduced milk production (agalactia)

 

TYPICAL GROSS FINDINGS:  

• Lungs:  

• Sheep: Heavy, pale gray or tan, diffusely firm to rubbery with rib imprints; failure to collapse; cut surfaces bulge but are not edematous or exudative; coinfection or   

• Goat: Diffuse or multifocal well-demarcated pale firm lesions; caudal lung lobes most severely affected

• Concurrent bronchopneumonia or lungworms may be superimposed
• Mediastinal and tracheobronchial lymph nodes enlarged, white, and edematous
• Arthritis: Swollen joints with thickened capsules; most commonly affects the carpal joints (carpal hygromas)
• Encephalomyelitis: Typically none; may have foci of malacia
• Mastitis: Udder firm, swollen; reduced milk production 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Lung:  

• Sheep (ovine progressive pneumonia, maedi) 

• Interstitial pneumonia; alveolar septa thickened by lymphocytes, plasma cells, and macrophages which coalesce into lymphoid nodules with germinal centers around vessels and airways
• Smooth muscle hypertrophy around terminal bronchioles and in alveolar septae
• Mild interstitial fibrosis

• Goats: 

• Chronic interstitial pneumonia with expansion of alveolar septa by lymphocytes, macrophages, and plasma cells; cuffs of lymphoid cells around blood vessels and airways
• Type II pneumocyte hyperplasia (this does NOT occur in sheep!)
• Alveoli filled with dense eosinophilic proteinaceous material (surfactant) and foamy macrophages

• Joint: Villous hyperplasia of synovial membrane with infiltration of lymphocytes and plasma cells
• Mammary gland: Massive infiltration of lymphocytes and plasma cells; degeneration, necrosis, and loss of acini and ducts; often subclinical lesion
• Artery: Non-suppurative arteritis of small muscular arteries and arterioles in carpal joint capsules, kidney, meninges, brain, lung and trachea
• CNS (N-V13): Lymphocytic leukoencephalomyelitis; mainly periventricular; zones of demyelination and malacia

 

ULTRASTRUCTURAL FEATURES:

 

ADDITIONAL DIAGNOSTICS: 

• Serology (AGID or ELISA) used for screening of flocks
• Quantitative PCR assays on blood or lung tissue
• Immunohistochemistry for p27, gp130 viral protein within macrophages in lesions

 

DIFFERENTIAL DIAGNOSIS:

• For respiratory lesions:
  • Peste des petits ruminants (morbillivirus): Can cause type II pneumocyte hyperplasia and alveolar edema; presence of bronchointerstitial pneumonia, syncytial cells, intranuclear or intracytoplasmic inclusions, and digestive tract lesions can help differentiate
  • Sheep:

• Ovine pulmonary carcinoma (Jaagsiekte sheep retrovirus, P-V16):  Prominent proliferative foci of cuboidal to columnar cells line alveoli and form papillary projections

• Mycoplasma ovipneumoniae (P-B02): Causes interstitial lymphoid cuffs and bronchiolitis; absence of smooth muscle hypertrophy
• Goats
• Muelleris capillaris can cause lymphocytic interstitial pneumonia 
• Mycoplasma capricolum subsp. capripneumoniae (contagious caprine pleuropneumonia, P-B02): Causes acute fibrinous pleuropneumonia
• Mannheimia haemolytica: causes sporadic acute bronchopneumonia, pleuritis in kids
• Pasteurella multocida: Less fulminating fibrinopurulent bronchopneumonia

 

 

COMPARATIVE PATHOLOGY:

• A recent study described an effort to eradicate CAEV in goats in an Italian province; found higher prevalence and seroconversion rate in goats in farms that also had sheep; sheep can serve as a SRLV genotype A reservoir and contribute to continued positive tests in goats (Nardelli, J Vet Diagn Invest 2020)

• Five SRLV genotypes: SRLV B most pathogenic in goats; SRLV A most pathogenic in sheep; SRLV A-C all cross species barrier

• Selected lentiviruses in other species

• Equine infectious anemia virus
• Human immunodeficiency virus
• Simian immunodeficiency virus (N-V14, P-V19)
• Bovine immunodeficiency virus
• Jembrana disease (cattle)
• Feline immunodeficiency virus

 

References:

1. Cantile C, Youssef S. Maxie MG, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, Palmer's Pathology of Domestic Animals. Vol.1. 6th ed. Philadelphia, PA: Elsevier; 2016:378-379.
2. Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, Palmer's Pathology of Domestic Animals. Vol. 2. 6th ed. Philadelphia, PA: Elsevier; 2016:558-559.
3. Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6^th ed. St. Louis, MO: Elsevier; 2016: 154-155.
4. López A, Martinson SA.  Respiratory system, mediastinum, and pleurae.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Mosby, Inc.; 2022:620-621.
5. Nardelli S, Bettini A, Capello K, et. al. Eradication of caprine arthritis encephalitis virus in the goat population of South Tyrol, Italy: analysis of the tailing phenomenon during the 2016-2017 campaign. J Vet Diagn Invest. 2020; 32(4): 589-593.
6. Zachary JF.  Mechanisms of microbial infections. In: Zachary JF, eds.  Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Mosby Elsevier; 2022:254.

 

 

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