JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2593663): An adult male cynomolgus monkey (Macaca fascicularis)
HISTORY: This monkey developed generalized, acute, multifocal to coalescing, erythematous and vesicular skin lesions and died.
MICROSCOPIC DESCRIPTION: Mucocutaneous junction, lip: Multifocally, expanding and disrupting the hyperplastic epithelium of the oral mucosa are multiple vesicles that contain enlarged, pale, sloughed epithelial cells that often form syncytial cells with up to 10 nuclei and multifocal eosinophilic intranuclear viral inclusion bodies that measure up to 15um and are surrounded by a clear halo with peripheralized chromatin. These cells are often individualized and are admixed with low numbers of neutrophils and pale flocculent eosinophilic material. Within the surrounding epithelium, cells are discohesive, often exhibit intracellular edema (hydropic degeneration), and often form similar syncytial cells with intranuclear viral inclusions. There is an ulcerated vesicle with similar sloughed cells, syncytial cells with intranuclear inclusions and flocculent material within the adjacent epidermis. Intranuclear viral inclusion bodies are also present within the subjacent sebaceous glands. There is hyperplasia of the mucosal epithelium and (to a lesser degree) the epidermis, with prominent rete ridges and spongiosis. Multifocally within both the superficial subepithelial connective tissue and dermis are areas of hemorrhage admixed with few neutrophils and few moderately ectatic lymphatics (edema). Multifocally, separating, surrounding, and occasionally replacing labial glands are moderate numbers of plasma cells, fewer Mott cells, occasional lymphocytes, macrophages, and rare neutrophils.
MORPHOLOGIC DIAGNOSIS: Mucocutaneous junction: Cheilitis, vesicular, multifocal, moderate, with viral syncytia, eosinophilic intranuclear viral inclusion bodies, epithelial hyperplasia, and mild lymphoplasmacytic hidradenitis, cynomolgus monkey (Macaca fascicularis), primate.
ETIOLOGIC DIAGNOSIS: Herpesviral dermatitis and cheilitis
CAUSE: Simian varicella virus (Cercopithecine herpesvirus 9)
ETIOLOGY SYNONYMS: Delta herpes, Liverpool vervet virus, patas herpesvirus, medical lake macaque virus
CONDITION: Simian varicella
- Simian varicella virus (SVV) is an alphaherpesvirus sharing similar antigenic properties with the human varicella-zoster (chickenpox/shingles) virus that affects a variety of Old World nonhuman primates; SVV affects the cutaneous, digestive, respiratory and lymphoid organs
- Acute, fatal, highly contagious, systemic disease of African green monkeys (Ceropithecus aethiops), pig-tailed macaques (Macaca nemestrina), Japanese macaques (Macaca fuscata), cynomolgus monkey (Macaca fascicularis), and patas monkeys (Erythrocebus patas)
- Simian varicella pathogenesis closely parallels fatal human varicella zoster virus; rapid spread via respiratory route with possible transmission through direct contact with skin lesions
- Attaches to host cell via surface heparin sulphates, engages mannose 6-phosphate receptor
- Transient viremia by day 3; virus transported in B and T cells
- Vesicular dermatitis by day 10 which is often hemorrhagic; lesions progress from papule to vesicle to crust
- By eight days the virus has disseminated to the liver, lungs, spleen, adrenal glands, kidneys, lymph nodes, and trigeminal ganglion, and causes necrotizing lesions in the liver, lungs and throughout the gastrointestinal tract
- Latency established within neural ganglia; competing hypotheses suggest hematogenous versus transaxonal transport to ganglia
- Disseminated, hemorrhagic vesicular exanthema with fever, pneumonia, and hepatitis
- Vesicular eruption first seen in inguinal region and spares palms and soles
- Animals may experience spontaneous resolution or a high fatality rate
TYPICAL GROSS FINDINGS:
- Lungs- edema, hemorrhage, necrosis and emphysema
- Diffuse ulcerative, hemorrhagic and necrotic gastrointestinal tract
- Generalized hemorrhagic epidermal rash with vesicle formation in skin, oral mucosa, and esophagus
- Necrosis - liver, spleen, lymph nodes, endocrine organs, and bone marrow
TYPICAL MICROSCOPIC FINDINGS:
- Cutaneous lesions- characterized by multiple vesicles within epidermis that contain debris, erythrocytes, and rare syncytial cells; hyperplasia of basal cell layer; eosinophilic Cowdry-type A intranuclear inclusions in cells adjacent to vesicle; necrotizing vasculitis in dermis with inclusions in endothelial cells
- Lungs - Hemorrhage and necrosis of alveolar walls and vasculature, ulcerated bronchiolar epithelium, vascular endothelial hyperplasia, intranuclear inclusions in endothelial cells, vascular smooth muscle and bronchial epithelium and a diffuse neutrophilic and histiocytic infiltrate
- Multifocal to diffuse necrosis and hemorrhage of liver, spleen, lymph nodes, adrenal cortex and bone marrow with intranuclear inclusions bordering foci of necrosis
- Enveloped, 150 nm diameter virions with a 100 nm icosahedral nucleocapsid
- Capsid surrounded by "tegument" enclosed by a lipoprotein envelope
- Envelope covered by small glycoprotein peplomers (heparan sulfate proteoglycan)
- Viral capsids form in the nucleus and bud through the nuclear membrane to acquire the cell derived envelope
ADDITIONAL DIAGNOSTIC TESTS:
- Electron microscopy
- Viral culture
- Macacine herpesvirus 1 (B virus)- commonly causes latent infection in young macaques via trigeminal and lumbosacral ganglia; Vesicles and ulcers may occur on dorsal surface of tongue, on the lip and the skin
- Monkey pox – syncytial cells, large eosinophilic intracytoplasmic inclusion bodies, generalized cutaneous rash and pocks
- Chimpanzee, gorilla, and orangutan varicella virus causes a mild self-limiting vesicular dermatitis
- Bailey C, Mansfield K. Emerging and reemerging infectious diseases of nonhuman primates in the laboratory setting. Vet Pathol. 2010;47:462-481.
- Gray GL. Simian varicella in old world monkeys. Comp Med. 2008;58:22-30.
- Jones TC, Hunt RC, King NW. Diseases Caused by Viruses. In: Veterinary Pathology, 6th ed. Baltimore, MD: Williams & Wilkins; 1997:222-223.
- MacLachlan NJ, Dubovi EJ. Herpesvirales. In: Fenner’s Veterinary Virology. 4th ed. San Diego, CA: Elsevier, Inc.; 2011:188.
- Murphy HW. Great apes. In: Miller RE, Fowler ME, ed. Fowler’s Zoo and Wild Animal Medicine. Vol 8. Louis, MO: Elsevier Saunders; 2015: 348.
- Ouwendijk WJD, Verjans GMGM. Pathogenesis of varicelloviruses in primates. J Pathol. 2015;235:298-311.
- Wachtman L, Mansfield K. Viral diseases of nonhuman primates. In: Abee CR, Mansfield K, Tardiff S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases Vol 2. San Diego, CA: Elsevier Inc.; 2012:17-18.