Mouse encephalomyelitis virus (mouse polio)

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

April 2017

N-V05 (NP)

 

Signalment (JPC Accession # 1327071):  Mouse

 

HISTORY:   None

 

HISTOPATHOLOGIC DESCRIPTION:  Cerebrum:  Diffusely the neuropil is pale and vacuolated and blood vessels are congested. Multifocally, there are few scattered degenerate neurons that are swollen with loss of Nissl substance and large vacuoles that distend the perikaryon. Frequently, degenerate neurons are surrounded by neutrophils, gitter cells that are phagocytizing myelin and neuronal debris (neuronophagia), and scattered karyorrhectic and cellular debris.

 

MORPHOLOGIC DIAGNOSIS:  Cerebrum:  Neuronal necrosis, multifocal, with spongiosis, strain unspecified, mouse.

 

ETIOLOGIC DIAGNOSIS:  Picornaviral encephalitis

 

CAUSE:  Mouse encephalomyelitis virus (MEV)

 

ETIOLOGY SYNONYMS:  Theilovirus (ThV), Theiler’s murine encephalomyelitis virus (TMEV)

 

CONDITION:  Mouse polio

 

GENERAL DISCUSSION: 

·       Single-stranded RNA cardiovirus of the Picornaviridae family; an enteric virus with numerous strains (TO, GDVII, FA, DA, and BeAn, among others) that in natural infection is typically asymptomatic but in immunodeficient mice can enter the CNS and cause neurologic disease

·       Highly neurovirulent strains (GDVII, FA) cause severe fatal encephalitis, regardless of inoculation route

·       Less virulent strains (TO, BeAn, DA) cause a biphasic disease with acute poliomyelitis initially that in susceptible mice (SJL) is followed by a late-onset demyelinating disease

·       Experimentally-induced MEV infection is used as an animal model for human poliomyelitis (acute poliomyelitis) and multiple sclerosis (late-onset demyelination)

 

PATHOGENESIS:

·       Natural transmission via fecal‑oral route with transient viremia limited by host immune response

·       Endothelial cells may facilitate entry into brain

·       Virus targets neurons and glia of hippocampus, thalamus, brainstem, and spinal cord

·       CNS viral persistence may occur for over a year with white matter-restricted residual infection and viral replication in macrophages, leukocytes, astrocytes, and oligodendrocytes

·       Demyelination results from the host immune response to the infected white matter in the spinal cord, brainstem, and cerebellum

 

TYPICAL CLINICAL FINDINGS: 

·       Under natural conditions, there is rarely clinical disease in immunocompetent mice

·       Acute poliomyelitis results in flaccid limb paralysis and high morbidity and mortality in exposed immunodeficient mice

·       Gait disorders, tremors, ataxia, extensor spasm, and urinary incontinence in late-onset demyelination phase

 

TYPICAL GROSS FINDINGS: 

·       None in the intestine or CNS

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

·       Acute phase (poliomyelitis): 

o   Neuronal necrosis, neuronophagia, microgliosis, nonsuppurative meningitis, and perivasculitis most prevalent in brainstem and ventral horns of spinal cord

o   In SCID and nude mice, marked neuronal vacuolation and enlargement, vacuolation of adjacent astrocytes and oligodendrocytes, and minimal to no inflammation

·       Late phase (demyelination): 

o   Nonsuppurative spinal meningitis and leukomyelitis

o   Multifocal white matter spongiosis, spheroids, and gitter cells

o   Acute myositis and focal myocarditis with IP inoculation

 

ULTRASTRUCTURAL FINDINGS:

·       Nonenveloped, 27nm diameter, icosahedral virions in paracrystalline arrays

·       Vesicular degeneration of myelin and stripping by macrophages

 

ADDITIONAL DIAGNOSTIC TESTS:

·       Serology (hemagglutination-inhibition, neutralization, enzyme immunoassay)

·       Virus isolation

·       Immunohistochemistry

 

DIFFERENTIAL DIAGNOSIS:

For microscopic findings:

·       Mouse hepatitis virus (Coronaviridae; coronavirus):  Neurotropic strains cause nonsuppurative encephalitis with spongiosis and demyelination in brainstem; viral-induced leukocytic, endothelial, or parenchymal syncytia in target organs

·       Lactate dehydrogenase elevating virus (Coronaviridae; arterivirus):  Non-suppurative encephalitis and scattered neuronal necrosis in ventral and dorsal horns of spinal cord of immunosuppressed C58 and AKR mice; nonsuppurative meningitis, myelitis, and radiculitis without clinical signs in C57 mice

·       Polyomavirus (Papovaviridae):  Nude mice develop infection of oligodendroglia with demyelination

·       Reovirus-3 (Reoviridae; orthoreovirus):  Acute diffuse encephalitis, focal necrotizing myocarditis and hepatitis, lymphoid necrosis, pancreatitis, and sialodacryoadenitis in experimentally-inoculated neonatal mice

·       Encephalomyocarditis virus (Picornaviridae; cardiovirus):  Rodents are natural reservoir; rarely causes encephalomyelitis in wild rodents but is not known to infect laboratory mice

 

COMPARATIVE PATHOLOGY:

Important Picornaviridae:

GENUS

VIRUS

SPECIES AFFECTED

DISEASE

Aphthovirus

Foot and Mouth Disease Virus

Wild & Domestic Ruminants, Swine

Foot and Mouth Disease

Enterovirus

Swine Vesicular Disease Virus

Swine

Swine Vesicular Disease

 

Avian Encephalomyelitis Virus

Chickens, Quail, Turkeys, Pheasants

Avian Encephalomyelitis/Epidemic Tremor

 

Duck Hepatitis Virus

Ducks

Duck Hepatitis

 

Polioviruses 1-3

Humans

Poliomyelitis

 

Coxsackieviruses

Humans

Hand-Foot-and-Mouth Disease

Cardiovirus

Encephalomyocarditis Virus

Primarily Swine, African Elephants; Also Humans, Monkeys, Cattle, Horses

Encephalomyocarditis

 

Theiler's Murine Encephalomyelitis Virus

Mice

Murine Poliomyelitis

Hepatovirus

Simian Hepatitis A Virus

Monkeys

Hepatitis

 

Human Hepatitis A Virus

Humans

Hepatitis

Rhinovirus

Human Rhinoviruses

Humans

Common Cold

Teschovirus

Porcine Teschoviruses

Swine

Teschen/Talfan Disease; Benign Enzootic Paresis

 

 

References:

1.      Laborde JM, Carbone C, Corva SG, Galosi CM. Evaluation of an indirect enzyme-linked immunosorbent assay for routine screening of Theiler’s murine encephalomyelitis virus antibodies in mice colonies. J Vet Diagn Invest. 2008;20:789-791.

2.      MacLachlan NJ, Dubovi EJ. Fenner’s Veterinary Virology. 4th ed. Oxford, UK: Elsevier; 2011:438-439.

3.      Oleszak EL, Chang JR, Friedman H, Katsetos, Platsoucas CD. Theiler's virus infection: Model for multiple sclerosis. Clin Micro Rev. 2004;17:174-207.

4.      Percy DH, Barthold SW. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing Professional; 2016:35-36.

5.      Summers BA, Cummings JF, de Lahunta A. Veterinary Neuropathology. St. Louis, MO: Mosby-Year Book, Inc; 1995:123-125.

 


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