October 2024

D-V12 (NP)

Signalment (JPC #1171326): A guinea pig

HISTORY: Incidental finding

HISTOPATHOLOGIC DESCRIPTION: Salivary gland: Multifocally within periductal areas the interstitium is expanded by moderate numbers of lymphocytes and fewer plasma cells and macrophages, admixed with small amounts of necrotic cellular and karyorrhectic debris. Multifocally, rare acinar cells are enlarged up to ten times normal (cytomegaly), with abundant eosinophilic granular cytoplasm and one to two nuclei containing an 8-12 µm diameter, deeply eosinophilic, round to oval intranuclear inclusion body which marginates the chromatin (“owl eye cells”). Multifocally, there is deeply basophilic mineral.

MORPHOLOGIC DIAGNOSIS: Salivary gland: Sialoadenitis, lymphoplasmacytic, multifocal, mild, with rare acinar cytomegaly with intranuclear inclusions, guinea pig (Cavia porcellus), rodent.

ETIOLOGIC DIAGNOSIS: Herpesviral sialoadenitis

CAUSE: Guinea pig cytomegalovirus (GPCMV); Caviid herpesvirus 2

GENERAL DISCUSSION:

Cytomegaloviruses belong to the family Herpesviridae, subfamily betaherpesvirus; species-specific
1. Enveloped linear dsDNA virus with fibrous core, icosahedral capsid
2. Replicates in host cell nucleus; slowly cytolytic and causes cytomegalic inclusion disease (eosinophilic intranuclear and intracytoplasmic inclusions) acquires envelope by budding through the host nuclear membrane; fragile, does not survive in environment
3. Can take many forms as multiple tissues can be infected
Transmission requires close contact with infected body secretions (e.g. coitus, nursing, closely confined populations)
Latent phase, with relapses during periods of stress
1. Persists in glandular tissue, lymphoreticular cells, and kidneys
2. Periodically shed in body secretions
Common incidental finding in guinea pigs, affecting up to 70-80% of adults, salivary gland most commonly affected
Animal model for congenital human cytomegalovirus infection
Natural and experimental infection have shown to cause abortion, stillbirth, and neonatal mortality

PATHOGENESIS:

Transmission via oronasal exposure to infected saliva or urine and transplacentally
Guinea pigs are used as an animal model because both humans and guinea pigs have hemochorial placentation with a single trophoblast layer; transplacental transmission and fetal infection occur in both species
Maternal and fetal outcomes are dependent on many variables (timing and route of infection, strain of guinea pig, source of virus and maternal immunity); viral inoculation early in pregnancy tends to lead to pup resorption, whereas challenge in late pregnancy tends to lead to pup mortality; maternal immunity may reduce in utero transmission and improve fetal outcomes
Salivary glands, kidney, and liver are the primary target tissues for GPCMV in the guinea pig

TYPICAL CLINICAL FINDINGS:

Experimentally infected neonates have shown growth retardation, thymic involution and splenomegaly
Congenital infection can be associated with encephalitis and labyrinthitis

TYPICAL GROSS FINDINGS:

Experimentally infected dams developed visceral lesions in the salivary gland, liver, spleen, lung, and liver
Rare acute systemic form will result in multifocal areas of necrosis in lymph nodes, spleen, liver, kidney, and lungs

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Lesions are primarily to the ductal epithelial cells of the salivary glands
Karyomegaly with large eosinophilic intranuclear inclusion bodies that marginate chromatin (“owl eye cells”); intracytoplasmic inclusions are occasionally present
Lymphoplasmacytic (mononuclear)inflammation
Interstitial pneumonitis and multifocal necrosis within lymph nodes, spleen, liver, kidney, and lung may be present in acute systemic form of the disease

DIAGNOSIS:

Viral isolation from actively shedding animals
Serology (ELISA)
In situ hybridization (ISH)
Immunohistochemistry (IHC)

DIFFERENTIAL DIAGNOSIS: (For intranuclear inclusions)

Guinea pig herpes-like virus (Caviid herpesvirus 1): Lymphotropic virus isolated from many strains of experimentally infected guinea pigs; no clinical signs; no gross or microscopic lesions; produces intranuclear inclusions in degenerating kidney cell cultures
Guinea pig X virus (Caviid herpesvirus 3): Experimentally, Hartley guinea pigs develop focal hepatic necrosis and mortality; has not been shown to cause natural disease, but could be a complicating factor in laboratory animals
Guinea pig adenovirus infection: Large basophilic intranuclear inclusions in respiratory epithelium; severe pneumonia

COMPARATIVE PATHOLOGY:

CMV in other species:

Rodents:
- Mice (mouse CMV): Studied for animal model of HCMV using original or derivatives of the Smith strain; wild mice commonly infected but show no overt disease, uncommon in laboratory mice, no placental transmission)
- Rats (rat CMV, common in wild rats, but nonexistent in laboratory rats)
- Chinese hamsters (Cricetid herpesvirus, CrHV-1); usually asymptomatic, inclusion body sialoadenitis; does not cross the placenta
Swine (Suid herpesvirus-2, CMV)
- Inclusion body rhinitis: mild to severe nonsuppurative necrotizing rhinitis in suckling piglets 3-5 weeks of age; histologically, there are large 8-12µm basophilic intranuclear inclusion bodies within the epithelial cells of nasal mucosal glands/ducts; may go systemic in piglets <3 weeks old, affecting the kidneys and other organs and death without premonitory signs
- Porcine cytomegalovirus abortion: When pregnant sows are infected, they may deliver small litters, mummified fetuses, or stillborn or weak piglets
- Acute viral glomerulonephritis is a common finding in neonates
Non-human primates: Common, asymptomatic, host-specific, latent infection in many species of NHP (new world and old world monkeys)
- Macaques (macacine herpesvirus-3): most are seropositive by 6 months old; can cause disease in immunosuppressed (common with SIV or SRV or drug therapy with cyclophosphamide, cortisone, and antithymocyte globulin), including disseminated necrotizing lesions in the brain, lymph nodes, liver, spleen, kidney, small intestine, and nervous system
- Chimpanzees: develop disseminated CMV infection in captivity; occasional intranuclear inclusions in myocardium, retina, brain, salivary gland, spleen, lymph node, stomach, tonsil, pancreas, intestine, arteries, and adrenal gland
- Other primates that have their own CMV specific virus are capuchin monkeys, woolly monkey, squirrel monkeys, chimpanzees, baboons, drill monkeys, saddleback tamarins and African green monkeys
Bovids (bovine herpesvirus-4, BoHV-4, Movar virus): An important cause of abortion in cattle (and occasionally swine); classified as a gammaherpesvirus; also responsible for infectious bovine cervicovaginitis and epididymitis (epivag) in African bovids; other wide variety of clinical conditions include pneumonia, enteritis, metritis, and mammillitis
Bats: CMV has been detected in the acinar cells of the submandibular gland of two captive Myotis lucifugus; asymptomatic with cytomegaly microscopically
Hedgehogs: CMV has been isolated from the salivary glands of asymptomatic African hedgehogs with cytomegalic inclusion disease (CID)
Humans (human cytomegalovirus, HCMV or human herpesvirus-5, HHV5): Most frequent congenital infection worldwide; leading cause of sensorineural hearing loss, developmental delay, and neurological deficits; transplacental transmission during maternal viremia

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