JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2023

N-V18 (NP)

 

Signalment (JPC #0875478): A mouse 

 

HISTORY: This mouse was experimentally infected with an infectious agent; the animal exhibited signs of drowsiness, emaciation, and roughened hair coat.

 

HISTOPATHOLOGIC DESCRIPTION: Cerebrum and brainstem: Multifocally infiltrating the leptomeninges as well as the ependymal lining of the ventricles are moderate to high numbers of lymphocytes, plasma cells, and rare neutrophils. A similar infiltrate multifocally extends from the meninges into the neuropil and surrounds vessels (perivascular cuffing), expanding the Virchow-Robin space, and multifocally extends from the ependymal lining into the periventricular neuroparenchyma. The submeningeal neuropil diffusely contains increased clear space and occasional eosinophilic amorphous fluid (edema) and multifocal hemorrhage with fibrin. Low numbers of lymphocytes infiltrate the choroid.

 

MORPHOLOGIC DIAGNOSIS: Cerebrum: Meningoencephalitis and ventriculitis, lymphoplasmacytic, multifocal, mild to moderate, with perivascular cuffing and mild choroiditis, mouse, breed unspecified, murine.

 

ETIOLOGIC DIAGNOSIS: Arenaviral choriomeningitis

 

CAUSE: Lymphocytic choriomeningitis virus (LCMV); Arenavirus

 

CONDITION: Lymphocytic choriomeningitis

 

GENERAL DISCUSSION: 

• Arenavirus (family Arenaviridae); ssRNA virus
• Zoonotic
• Named for the ability to produce lymphocytic choriomeningitis in intracerebrally inoculated mice and monkeys; this is not a feature of natural infection
• The mouse is the natural host; the hamster and mouse are the primary sources for human infection 

 

PATHOGENESIS:

• Maintained by persistently infected mice that shed virus in saliva, urine, and feces
• Vertical infection is a major means of transmission in mouse populations
  • Infected fetal and neonatal mice develop immune tolerance and become persistently infected 
  • Some LCMV-specific antibody is produced à complex with excess viral antigen à deposited in tissues (arterial walls, choroid plexus, glomeruli) à eventually develop lymphocytic infiltrates in many tissues, vasculitis, and immune complex glomerulonephritis
• Natural infection of immunocompetent adults result in short term, acute infection from which they recover and seroconvert
• Experimental infections follow a different course depending on route of administration, virus strain, mouse age, and genotype
  • Aggressive strains produce host response with CD8+ T cell-mediated disease
  • Docile strains cause immune exhaustion with no clinical T cell-mediated disease
    • Immune exhaustion results in marked lymphoid depletion and severe immunodeficiency
• Definitive diagnosis of LCMV cannot be based on pathology alone

 

TYPICAL CLINICAL FINDINGS:

• Dependent on virus strain, mouse age, genotype, and route of infection
• Runting of infant mice and chronic wasting in older mice

 

TYPICAL GROSS FINDINGS:

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• In persistently infected mice, vasculitis and lymphocytic infiltrates in a variety of tissues
• Immune mediated glomerulonephritis
• Acute disease results from experimental inoculation and can produce nonsuppurative choriomeningitis, necrotizing hepatitis, and lymphoid depletion

 

ULTRASTRUCTURAL FINDINGS:

 

ADDITIONAL DIAGNOSTIC TESTS:  

• PCR
• Serology
  • Must be applied to a large sample size in order to detect immunotolerant mice within a colony
  • Adult sentinels housed with persistently infected mice will seroconvert and enhance diagnosis via serology
• Intracerebral inoculation of adult mice (LCMV is the only virus of mice currently recognized that will kill adults, but not neonates, when inoculated intracerebrally)

 

DIFFERENTIAL DIAGNOSIS:

• Chronic illness in older mice:
  • Glomerulonephritis associated with other persistent viral infections or immune disorders
  • Chronic renal disease of aging mice
  • Amyloidosis
  • Generalized lymphoproliferative disorders
• Runting in infant mice:
  • Murine adenovirus-1 and -2, reovirus, other viral infections

 

COMPARATIVE PATHOLOGY: 

LCMV in other species:

• Humans – 3 syndromes
  • Fever, headache, myalgia, malaise – most common
  • Aseptic meningitis
  • Severe encephalomyelitis
• Guinea pigs 
  • Highly susceptible to interstitial pneumonia when infected experimentally
• Hamsters – all ages are susceptible to persistent infection 
  • Amplify virus; very high zoonotic risk
  • Clinical disease is rare
• New World Monkeys – Marmoset (callitrichid) hepatitis (D-V27)
  • Tamarins and marmosets
  • Acute, fatal epizootic disease
  • Transmitted via contact with or ingestion of infected mice
  • Clinical signs:  Dyspnea, weakness, jaundice
  • Gross lesions:  Hepatomegaly, splenomegaly, pleural & pericardial effusion, and SQ & IM hemorrhage
  • Histo lesions:  Multifocal hepatic necrosis, prominent hepatocellular swelling, intracytoplasmic acidophilic inclusions, +/- lymphoplasmacytic meningitis

 

References:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley & Sons, Inc; 2016: 23-25,178.
2. Mätz-Rensing K, Lowenstine LJ. New World and Old World Monkeys. Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Academic Press; 2018: 355-356.
3. Wachtman L, Mansfield K. Viral Diseases of Nonhuman Primates. In: Abee, ed. Nonhuman Primates in Biomedical Research: Diseases. Volume 2. San Diego, CA: Elsevier Inc; 2012:54-56.

 

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