JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2026 P-V10

HISTOPATHOLOGIC DESCRIPTION:

Lung: Diffusely, bronchial and bronchiolar epithelium is either sloughed or necrotic with shrunken, hypereosinophilic cytoplasm and pyknotic nuclei, or is degenerate with swollen cytoplasm and loss of cilia. There are frequent multinucleated viral syncytial cells of the bronchial and bronchiolar epithelium. Epithelial and syncytial cells multifocally contain 4 µm, eosinophilic, intranuclear inclusion bodies that marginate the chromatin. The bronchiolar submucosa is expanded by necrotic debris, viable and necrotic neutrophils, macrophages, fibrin, hemorrhage, and edema. Multifocally, alveolar septa are replaced by eosinophilic cellular debris (septal necrosis) or expanded by neutrophils and macrophages. Alveolar epithelial cells are covered by a brightly eosinophilic, 7µm thick layer of polymerized fibrin (hyaline membrane). Alveolar spaces frequently contain a variable amount of fibrin, hemorrhage, edema, scattered necrotic cellular debris, and neutrophils. Diffusely, the subpleural space, intralobular septa, perivascular, peribronchial, and peribronchiolar areas are markedly expanded up to 500µm by abundant hemorrhage, fibrin, edema, and few macrophages, neutrophils, and lymphocytes.

GENERAL DISCUSSION:

• Equid herpesvirus 1 (EHV-1), family Herpesviridae, subfamily Alphahepesvirinae, genus Varicellovirus
• EHV-4 may cause similar disease; less common and sporadic without systemic neurologic or abortions
• Worldwide distribution
• Respiratory, neurologic, systemic neonatal disease, abortion with first exposure before 1yo.Equine Gammaherpesvirus 5 may also cause interstitial pneumonia, but within the first month of life (Ochi et al 2026)

PATHOGENESIS:

• Pulmonary (EHV-1 and EHV-4): Virus infects nasal respiratory epithelial cells > virus replication in the nasopharynx > local epithelial necrosis and inflammation > rhinitis, nasal discharge > virus shed 2-10 days post infection during pyrexia (virus shedding can last up to 3 weeks) >latency established in neuronal cells (ex. trigeminal ganglion), lymphocytes, and lung epithelial cells (EHV-4 only)
  • Rarely extends to the trachea
  • Viremia dependent on the strain of the virus and prior exposure of the host
• Systemic (EHV-1 only): Virus infects nasal respiratory epithelial cells > virus replication in the nasopharynx and associated lymphoid tissue > virus transported to sites of secondary infection by monocytes > endothelial cell infection > inflammation/vasculitis, thrombosis, and tissue necrosis due to infarction
• Seroconversion is common; nearly 100% of horses have EHV-4 seroconversion
• S. zooepidemicus and other streptococci are common respiratory co-isolates
• Classic low-level immunity; common with herpesviruses
• Abortion: See R-V01 – Equine Viral Abortion for detailed pathogenesis of EHV-1 abortions
  • Mares that abort generally do not experience respiratory disease

TYPICAL CLINICAL FINDINGS:

• Juvenile and adult horses
  • Usually uncomplicated rhinitis; febrile; mucopurulent nasal discharge
  • Cough if the infection extends to trachea, less common
  • Rarely fatal unless complicated by secondary bacterial infection
  • Late term abortion
• Young horses: Rare; biphasic fever, depression, anorexia, coughing and nasal and ocular discharge; may lead to secondary bacterial infection lasting 2-3 weeks

TYPICAL GROSS FINDINGS:

• Aborted fetus:
  • Consistent severe pulmonary edema; lungs are heavy and rubbery with impressions of the ribs and pitting under pressure; edema of interlobular septa; lungs may be darker or lighter than normal with multiple 2-4 mm tan to white foci of necrosis and petechial hemorrhages; casts of fibrin and sloughed epithelial cells in bronchi and trachea
  • Petechia and ecchymoses throughout body, but most common in the upper respiratory mucosae
  • Edema of subcutis and fascia; amber fluid in body cavities
  • Slight icteric discoloration and meconium staining of the eponychia and amnion
  • 50% of aborted fetuses have minute to 5 mm, gray to white foci of necrosis in the liver
  • Occasional hemorrhagic necrosis of renal cortices
• Neonatal foals
  • Lungs are heavy with a diffuse rubbery-firm texture; multifocal areas of inconspicuous focal necrosis
  • Necrosis of intestinal crypts with hemorrhage may be observed
• Yearlings or adult horses
  • Rare systemic disease
  • Pulmonary or systemic necrotizing vasculitis; pulmonary edema and hemorrhage; lymphoid necrosis; encephalomyelitis with vasculitis
• Foals may be born alive, but it is unknown whether any survive

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Aborted fetus
  • Pulmonary interlobular septa are edematous and contain mononuclear inflammation; edema, hemorrhage, and necrosis throughout lung; fibrinous alveolar exudation and necrosis of bronchial and alveolar epithelial cells
  • Acidophilic intranuclear inclusion bodies in the bronchial and alveolar epithelial cells are specific
  • Liver lesions are minute and may be overlooked; inconsistently there are few intranuclear acidophilic inclusion bodies in hepatic parenchymal cells; focal necrosis; edema; leukocytes admixed with necrosis and within portal regions
  • Rarely, diffuse hepatitis without focal necrosis
  • Necrosis of germinal centers in splenic follicles, thymus and other lymphoid tissues; focal splenic hemorrhage; rare inclusions
  • No placental lesions
• Neonatal foal
  • Severe bronchointerstitial pneumonia; multifocal necrosis in liver, spleen, adrenal gland, and other tissues; prominent intranuclear inclusion bodies; rare syncytia
• CNS: Characteristic lesion is nonsuppurative necrotizing vasculitis and thrombosis

ULTRASTRUCTURE:

• Enveloped, 150 nm diameter virions with a 100 nm icosahedral nucelocapsid
• Capsid surrounded by "tegument" enclosed by a lipoprotein envelope
• Envelope covered by small glycoprotein peplomers (heparan sulfate proteoglycan)

ADDITIONAL DIAGNOSTIC TESTS:

• Serology is not useful due to widespread exposure and frequency of seroconversion
• Frequently PCR positive animals are not viremic (Pusterla et al 2025)

DIFFERENTIAL DIAGNOSIS:

Viral respiratory infections in foals:

• Equine arteritis virus (Arterivirus, Arteriviridae) - Rapidly progressive bronchointerstitial pneumonia and intestinal necrosis in foals and yearlings; no inclusions
• Equine adenovirus (Mastadenovirus, Adenoviridae) in SCID foals - Bronchiolitis and pneumonia, pancreatic and salivary gland necrosis; basophilic INIB
• EHV-2 (Equine Cytomegalovirus, Gammaherpesvirus) - Purulent nasal discharge and lymphadenopathy
• EHV-3 (Equine coital exanthema, Alphaherpesvirus) - Subclinical respiratory infection in yearling horses
• EHV-4 (Equine rhinopneumonitis, Alphaherpesvirus) - Acute respiratory disease in foals > 2 months, weanlings and yearlings; less common and sporadic
• EHV-5 (P-V27) (Equine multinodular pulmonary fibrosis, Gammaherpesvirus) – Multinodular pulmonary fibrosis
• Equine paramyxoviral pneumonia (P-V26) (Hendra virus; family Paramyxoviridae, genus Henipavirus) - Marked pulmonary edema with gelatinous sub-pleural lymphangiectasia; diffuse alveolar edema with vasculitis, capillary thrombosis, ectatic lymphatics, fibrinous exudate, hemorrhage, and syncytial cells within vessels
• African horse sickness (Orbivirus; family Reoviridae) – Massive pulmonary edema

COMPARATIVE PATHOLOGY:

Herpesviral Respiratory Diseases:

• Guinea Pigs: Equine Herpesvirus 1 associated with neurologic disease, abortions and still births
• Canine Herpesvirus (U-V03) (Canine Herpesvirus 1, Alphaherpesvirus)
• Feline Herpesvirus (P-V09) (Feline Herpesvirus 1, Alphaherpesvirus)
• Infectious Bovine Rhinotracheitis (Bovine Herpesvirus 1, Alphaherpesvirus)
• Malignant Catarrhal Fever (D-V15, S-V01, U-V02) (Alcelaphine Herpesvirus 1 or Ovine Herpesvirus 2, Gammaherpesviruses)
• Bovine Herpesvirus (Bovine Herpesvirus 4)
• Caprine Herpesvirus (Caprine Herpesvirus 1, Alphaherpesvirus)
• Pseudorabies (N-V07) (Suid Herpesvirus 1, Alphaherpesvirus)
• Porcine Cytomegalovirus (P-V13) (Porcine Herpesvirus 2, Betaherpesvirus)
• Avian Infectious laryngotracheitis (P-V11) (Gallid Herpesvirus 1, Alphaherpesvirus)
• OWM & NWM NHP and Apes (Cytomegaloviruses, Betaherpesviruses): several species are human-derived zoonotic (ex. B virus, human simplex virus)
• Apes: Human Herpesvirus (Human Herpesvirus 1 & 2, Alphaherpesviruses): Chimpanzee Alphaherpesvirus ChHV only verifiable ape-specific
• Elephant Endotheliotropic Herpes Virus (EEHV) Disease (C-V05) (EEHV 1-7, Betaherpesvirus)
• Rabbits (Leporid Herpesvirus 3, Gammaherpesvirus): note rabbits are extremely sensitive to human herpesvirus 1 with nonsuppurative meningoencephalitis

REFERENCES:

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