Equine Herpesvirus 1, 4, and 5 Study Guide

Overview and Clinical Importance

Equine herpesviruses (EHV) are among the most clinically significant viral pathogens affecting horses worldwide. The family includes nine identified herpesviruses, with EHV-1, EHV-4, and EHV-5 being the most important for NAVLE preparation. These viruses are ubiquitous in horse populations, with estimates suggesting that 60-80% of horses harbor latent infections.

EHV-1 and EHV-4 are alphaherpesviruses that cause respiratory disease (rhinopneumonitis), while EHV-1 additionally causes abortion, neonatal foal death, and the devastating neurologic form known as equine herpesvirus myeloencephalopathy (EHM). EHV-5 is a gammaherpesvirus associated with equine multinodular pulmonary fibrosis (EMPF).

Viral Classification and Characteristics

Taxonomic Classification

EHV-1 Strain Variation: The D752/N752 Polymorphism

A critical concept for NAVLE is understanding the DNA polymerase (ORF30) single nucleotide polymorphism that distinguishes neuropathogenic from non-neuropathogenic strains. At amino acid position 752:

• D752 (Aspartic acid): Associated with increased neuropathogenic potential, higher and longer viremia, found in approximately 75-86% of EHM outbreaks
• N752 (Asparagine): Wild-type strain, causes 95-98% of abortion outbreaks but can still cause EHM (15-25% of neurologic outbreaks)
• H752 (Histidine): Recently identified third variant (C2254), pathogenic potential still under investigation

Pathogenesis

EHV-1 and EHV-4: Respiratory Disease Pathway

Stage 1: Primary Infection of Upper Respiratory Tract

Transmission: Direct nose-to-nose contact, aerosolized respiratory secretions, fomites (contaminated equipment, hands, clothing). The incubation period is 2-10 days.

Initial replication: Virus replicates in epithelial cells of nasal septum, nasopharynx, and trachea in a restricted, plaque-wise manner. Viral plaques appear 2-7 days post-inoculation. Destruction of respiratory epithelium causes serous nasal discharge that may become mucopurulent with secondary bacterial infection.

Stage 2: Cell-Associated Viremia (Critical for EHM and Abortion)

Following epithelial infection, EHV-1 crosses the basement membrane using infected leukocytes as a "Trojan horse". The primary carrier cells are:

• CD172a+ monocytic cells (primary carriers)
• T lymphocytes (especially CD4+ cells)
• B lymphocytes

Infected leukocytes reach draining lymph nodes (submandibular, retropharyngeal, bronchial) where infection is amplified. Discharge of infected cells into blood creates cell-associated viremia detectable from 1-14 days post-infection. The virus silences late gene expression in circulating leukocytes, preventing exposure of viral glycoproteins on the cell surface and allowing evasion of neutralizing antibodies.

Stage 3: Secondary Replication in Target Organs

Endothelial Cell Infection: Infected PBMC adhere to and transfer virus to endothelial cells lining blood vessels of target organs. This occurs via cell-to-cell contact mediated by adhesion molecules (ICAM, E-selectin, P-selectin on endothelium; integrins on leukocytes).

Pregnant Uterus (Abortion):

• Vasculitis and thrombosis of small arterioles in endometrial glandular layer
• Avascular necrosis and edema of endometrium
• May cause abortion of virus-negative fetus (placental detachment) or virus-positive fetus (transplacental infection)
• Abortions typically occur in last trimester (months 7-11), 2-12 weeks after infection

Central Nervous System (EHM):

• Vasculitis with or without hemorrhage in brain and spinal cord
• Thrombo-ischemic necrosis leads to neuronal degeneration
• Spinal cord is most commonly affected
• Neurologic signs appear 6-8 days after initial infection

Latency and Reactivation

EHV-1 establishes lifelong latent infection in the trigeminal ganglia, respiratory lymphoid tissues, and circulating T lymphocytes. It is estimated that greater than 60% of horses are latently infected. During latency, only latency-associated transcripts (LATs) are expressed, antisense to the immediate-early gene (ORF64).

Reactivation triggers include:

• Stress (transport, weaning, competition, hospitalization)
• Immunosuppression
• Corticosteroid administration
• Concurrent infections

EHV-5: Equine Multinodular Pulmonary Fibrosis (EMPF)

EHV-5 is strongly associated with EMPF, though whether it is causative, precipitating, or incidental remains under investigation. The virus establishes latency in T and B lymphocytes, which may serve as lifelong reservoirs. Despite EHV-5 being ubiquitous in horse populations, only a small percentage develop clinical EMPF, suggesting host-specific factors (age, immunologic response) play a role.

Pathologic findings: Progressive fibrosing interstitial lung disease with loss of functional pulmonary parenchyma. Multiple nodules of interstitial fibrosis form throughout the lungs, creating a characteristic radiographic and gross pathology appearance.

Clinical Presentations

Summary of Clinical Manifestations by Virus Type

Equine Herpesvirus Myeloencephalopathy (EHM) - Detailed Clinical Features

Classic clinical presentation includes:

• Fever (greater than or equal to 101.5°F/38.6°C): Often precedes neurologic signs by 24-48 hours
• Hindlimb weakness/ataxia: Ranges from mild incoordination to complete paralysis
• Urinary dysfunction: Bladder atony, urine dribbling, overflow incontinence
• Tail and anal hypotonia: Loss of tail tone, fecal incontinence
• Limb edema ("stocking up"): Due to impaired lymphatic return
• Dog-sitting posture: Classic finding in severe cases
• Recumbency: Poor prognostic indicator; 30-50% mortality in EHM cases

EHV-1 Abortion - Clinical Features

• Timing: Last trimester (months 7-11), typically 2-12 weeks post-infection
• Premonitory signs: Usually NONE - mare aborts suddenly without udder development or milk production
• Fetal condition: Fresh or minimally autolyzed, often still enclosed in membranes
• Fetal lesions: Subcutaneous edema, jaundice, excess pleural/peritoneal fluid, enlarged spleen, hepatic necrosis with 1mm white foci, pulmonary edema
• Mare: No reproductive tract damage; subsequent fertility unimpaired

Diagnosis

Preferred Diagnostic Methods

EHV-5/EMPF Diagnosis

• Thoracic radiography: Severe, diffuse, uniformly distributed nodular interstitial pattern
• Thoracic ultrasound: Multiple nodular densities, comet-tail artifacts
• BAL/Tracheal wash: EHV-5 PCR positive (found in 70-80% of cases); neutrophilia common
• Lung biopsy: Definitive diagnosis; interstitial fibrosis with collagen expansion, intranuclear inclusions in alveolar macrophages
• Blood work: Neutrophilia, hyperfibrinogenemia, hypoxemia on arterial blood gas

Treatment

Treatment Summary by Condition

Prevention and Vaccination

AAEP Vaccination Guidelines

Vaccine Types Available

• Inactivated (killed) vaccines: Available for respiratory disease and abortion prevention; high-antigen load products (Pneumabort-K, Prodigy) preferred for pregnant mares
• Modified-live vaccine (Rhinomune): Licensed for respiratory disease only; may reduce nasal shedding and fever; NOT for use in pregnant mares

Biosecurity and Outbreak Management

• Isolation: Immediate isolation of febrile or symptomatic horses
• Quarantine duration: Minimum 21 days from last case; restart 28-day clock if new cases identified
• Temperature monitoring: Twice daily for all exposed horses (greater than or equal to 101.5°F triggers isolation)
• Movement restrictions: Cease all horse movement in and out of facility during outbreak
• Disinfection: Virus easily killed by common disinfectants and detergents
• Reporting: EHM is reportable in most states; notify state veterinarian

Prognosis