JPC SYSTEMIC PATHOLOGY
RESPIRATORY SYSTEM
October 2023
P-V26
Signalment (JPC #2641092): Adult horse, breed and gender unspecified.
HISTORY: This horse was experimentally inoculated with Hendra virus. Seven days post-inoculation the horse developed tachycardia, tachypnea, anorexia and lethargy.
HISTOPATHOLOGIC DESCRIPTION: Lung: Multifocally, approximately 50% of alveolar septa are thickened up to 10X normal by fibrin, edema, increased numbers of macrophages and lymphocytes, and small aggregates of brown globular pigment within macrophages (hemosiderin). Multifocally, lumina of smaller bronchi, bronchioles, and alveoli contain variable amounts of edema admixed with hemorrhage and previously described inflammatory cells. Endothelial cells lining small to medium caliber blood vessels and alveolar capillaries occasionally form viral syncytial cells with up to six nuclei. Diffusely, perivascular, peribronchiolar, and subpleural interstitium and interlobular septa are markedly expanded by homogenous pale eosinophilic fluid or increased clear space (edema), previously described inflammatory cells, and ectatic lymphatics. Multifocally alveolar septa are discontinuous, forming large confluent airways (emphysema).
Kidney: Endothelial cells lining glomerular capillaries and renal vessels are often swollen (degeneration) or necrotic with occasional syncytial cell formation. Multifocally, the tunica media of arteries and arterioles is characterized by myocyte degeneration and fibrin deposition, and the tunica adventitia is mildly expanded by fibrosis and multifocally infiltrated or surrounded by lymphocytes and fewer macrophages and plasma cells. Rarely, glomerular tuft architecture is lost and replaced by thick, homogenous, eosinophilic collagenous material (glomerular sclerosis) or glomerular tufts are markedly shrunken (glomerular obsolescence). Medullary tubules occasionally contain granular basophilic material (mineral).
MORPHOLOGIC DIAGNOSIS: 1. Lung: Pneumonia, interstitial, lymphohistiocytic, multifocal, subacute, moderate, with endothelial viral syncytial cells and perivascular, interlobular, subpleural, and alveolar edema, breed not specified, equine.
2. Kidney: Endothelial degeneration and necrosis, multifocal to coalescing, with endothelial syncytial cell formation, multifocal arteriolar degeneration, and multifocal mild lymphoplasmacytic perivasculitis.
ETIOLOGIC DIAGNOSIS: Equine paramyxoviral (Hendraviral) pneumonia
CAUSE: Hendra virus
GENERAL DISCUSSIOIN:
- Hendra virus (HeV) is an enveloped, single stranded RNA virus with tropism for endothelial cells that causes an acute interstitial pneumonia with severely damaged endothelium and widespread alveolar edema
- It was first recognized in September 1994 during an outbreak in a stable in the Brisbane, Australia suburb of Hendra
- Fruit bats (flying foxes) in the genus Pteropus are the reservoir host
- Initially called equine morbillivirus, it is the prototype species of a relatively new genus Henipavirus within the family Paramyxoviridae; it is closely related to Nipah virus of swine which is also a member of this genus
- HeV is currently classified as a biolevel 4 pathogen because it has proven to be zoonotic; HeV equine vaccine released in November 2012 (HeVsG glycoprotein subunit-based)
- HeV is not highly infectious under natural or experimental conditions; natural transmission of virus to horses occurs sporadically
- HeV has been isolated from:
- Fetal tissues and blood of four species of fruit bats (flying foxes, family Pteropodidae) in Eastern Australia
- Oral cavity, saliva, and urine of infected horses
- Urine of experimentally inoculated cats
- Outbreaks in the Hendra and Mackay suburbs have been associated with the flying fox breeding season; bat urine, aborted bat fetuses or reproductive fluids containing virus are thought to be involved in transmission
PATHOGENESIS:
- The pathogenesis of HeV is not completely understood
- Horses can be experimentally infected by the oronasal route; transmission is thought to occur by the ingestion of pasture contaminated with urine or reproductive fluids from infected flying foxes
- Virus localizes in blood vessel walls in the lungs and other organs leading to endothelial cell damage and endothelial syncytial cell formation
- Ephrin-B2, a transmembrane protein expressed on endothelial cells, is the functional receptor for the henipaviruses
- Hendra virus P gene encodes proteins that interfere with interferon induction and signaling; pathogenicity is due to evasion of this interferon response
TYPICAL CLINICAL FINDINGS:
- Incubation period between 8 and 11 days (maximum of 16 days)
- Clinical course is short with high mortality; death occurs in approximately three days
- Acute respiratory distress, anorexia, fever, depression, and ataxia
- Copious yellow frothy nasal discharge, ataxia, and head pressing are common in the terminal stages
- Coughing is not a feature
TYPICAL GROSS FINDINGS:
- There is a notable absence of upper respiratory tract lesions
- Marked pulmonary edema and congestion with gelatinous distention of sub-pleural lymphatics; ventral consolidation of the lungs; excess thoracic and pericardial fluid
- Petechial hemorrhages on pleural surfaces; patchy hemorrhages of varying sizes within the parenchyma
- Fluid may ooze from cut surfaces; airways are often blocked by white to blood-tinged foam; trachea may contain abundant froth
- Other gross findings include visceral edema and petechial and ecchymotic hemorrhages in the perirenal tissue, stomach, and intestines
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Diffuse serofibrinous alveolar edema with vasculitis, capillary thrombosis, ectatic lymphatics, hemorrhage, and increased numbers of alveolar macrophages
- Endothelial syncytial cells are inconsistently present in small blood vessels and alveolar capillaries
- Subtle vascular lesions may be present in a wide range of organs including lung, heart, and kidney
- Inclusion bodies are not visible by light microscopy (except in guinea pig neurons)
ULTRASTRUCTURAL FINDINGS:
- Measures 38 to 600 nm; envelope has a unique double-fringed appearance due to surface projections of different lengths (15 and 18 nm)
ADDITIONAL DIAGNOSTIC TESTS:
- Virus readily detected in pulmonary endothelial cells and alveolar epithelial cells by immunohistochemistry or IFA
- Identification of characteristic virion structure on EM
- Virus isolation
- PCR and ELISA
DIFFERENTIAL DIAGNOSIS:
- Pulmonary form of African horse sickness
- Pulmonary edema, distended subpleural lymphatics, froth within the airways and failure of lungs to collapse
- Occurs in Africa, Middle East, India, Pakistan and Spain
- Equine viral arteritis (Arterivirus)
- Interstitial pneumonia with vasculitis, distended lymphatics and bronchioalveolar edema
- Occurs throughout the world
- Anaphylaxis
- Alveolar and interlobular edema, bronchoconstriction, congestion, emphysema and blood-tinged froth within airways
- Heart failure
- Edema with low protein content within interstitium and alveoli, erythrocytes and hemosiderin-laden macrophages (“heart failure cells”) within alveoli; white froth within airways
- Heart failure
COMPARATIVE PATHOLOGY:
- Golden hamster: Highly susceptible to experimental infection
- Cat: Develop a fatal pneumonia similar to the equine disease
- Guinea pig: Develop generalized vascular disease and encephalitis, but little or no pulmonary disease
- Mice, rats and dogs do not develop clinical disease nor seroconvert
- Rabbits do not develop clinical disease but seroconvert
References:
- Barclay AJ, Paton DJ. Hendra (equine morbillivirus). Vet Jour. 2000;160:169-176.
- Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier; 2016:569.
- Field HE, Mackenzie JS, Daszak P. Henipaviruses: emerging paramyxoviruses associated with fruit bats. Curr Top Microbiol Immunol. 2007;315:133-159.
- Hooper PT, Ketterer PJ, Hyatt AD, Russell GM. Lesions of experimental equine morbillivirus pneumonia in horses. Vet Pathol. 1997;34(4):312-322.
- Lopez, A. and Martinson, SA. Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO:Elsevier; 2022: 604.
- MacLachlan NJ, Dubovi EJ. Paramyxoviradae. In: MacLachlan NJ, Dubovi EJ, eds. Fenner’s Veterinary Virology. 4th ed. London, UK: Academic Press; 2011:321-323.
- Middleton D, Pallister J, Klein R, et al. Hendra virus vaccine, a one health approach to protecting horse, human, and environmental health. Emerg Infect Dis. 2014;20(3)372-379.
- Westbury HA. Hendra virus disease in horses. Rev Sci Tech. 2000;19:151-159.
- Williamson MM. Hendra virus infection. In: Coetzer JAW, Tustin RC, eds. Infectious Diseases of Livestock. Vol 2. 2nd ed. Cape Town, South Africa: Oxford University Press; 2004:681-686.
- Williamson MM, Torres-Velez FJ. Henipavirus: a review of laboratory animal pathology. Vet Pathol. 2010;47(5):871-880.
- Wang LF, Yu M, Hansson E, et al. The exceptionally large genome of Hendra virus: support for creation of a new genus within the family Paramyxoviridae. J.Virol. 2000;74(21):9972-9979.