Polyomaviruses



Polyomaviruses


John A. Vanchiere

Gail J. Demmler



Polyomaviruses are small DNA viruses that infect most humans, persist for life, and rarely cause disease. In patients who are severely immunosuppressed, however, polyomaviruses can produce serious illness of the central nervous system (CNS) or urinary tract. The polyomaviruses that infect humans include JC virus (JCV), BK virus (BKV), and simian virus 40 (SV40). Polyomaviruses, especially SV40, are named for their ability to cause tumors in laboratory animals, and they have been increasingly identified in human tumors, including tumors of the CNS, mesotheliomas, osteosarcomas, and lymphomas. In humans, these viruses are neurotropic, nephrotropic, and lymphotropic, with each virus having different affinities for each of these target organs.


JC VIRUS

Progressive multifocal leukoencephalopathy (PML) is a rare, demyelinating disease of the CNS seen in hosts who are immunosuppressed, most commonly in patients with acquired
immunodeficiency syndrome (AIDS). The causative agent—JCV—first was isolated in fetal glial cell culture in 1971 from the brain homogenate of a patient (initials, JC) with fatal PML. Although PML is a rare, opportunistic disease, infection with JCV is a common occurance in childhood, especially in school-aged children; 65% of 14-year-old children have antibody to the virus. JCV usually causes few or no symptoms, although it has been associated with mild respiratory illness. The virus can reactivate and be detected in the urine of normal pregnant women, renal and bone marrow transplant recipients, and children and adults with malignancies.


Pathology

The histopathologic changes seen in the brains of patients with PML consist of multiple areas of gross demyelination, enlarged hyperchromatic nuclei of the oligodendrocytes, and proliferation of bizarre-appearing astrocytes. Neurons are typically unaffected. Electron microscopy reveals large numbers of polyomavirus particles in the nuclei of oligodendrocytes, and viral antigen can be identified by immunofluorescence. While viral DNA can be detected easily by DNA hybridization assays and polymerase chain reaction (PCR), a striking lack of inflammatory response is evident in the brains of patients with PML. This disparate finding is not surprising given the profound T-cell immune suppression that predisposes patients to PML.


Clinical Manifestations

The diagnosis of PML should be considered in any immunocompromised host who develops a progressive, multifocal neurologic illness. Among adult patients with AIDS, PML has an incidence of nearly 5%, but it is much less common in children. PML often begins with personality and behavioral changes, altered mental status, hemiparesis, ataxia, aphasia, or cortical blindness and progresses to coma over a period of weeks to months. Death usually results in 2 to 4 months, although some patients have lived for 1 to 2 years. Paradoxically, the cerebrospinal fluid is often normal. The electroencephalogram shows diffuse and nonspecific slowing. Computed tomography (CT) of the brain reveals areas of demyelination.


Diagnosis

The diagnosis of PML may be suggested clinically in any immunocompromised patient who develops multifocal brain disease. Other neurodegenerative diseases of known or presumed viral etiology include multiple sclerosis, subacute sclerosing panencephalitis, herpesvirus infections of the CNS, and AIDS. A tentative diagnosis of PML can be made if CT or magnetic resonance imaging (MRI) shows areas of decreased density in the white matter areas of the brain.

Definitive diagnosis of PML is made by brain biopsy or by examination at autopsy. The unique histopathology usually establishes the diagnosis. Polyomavirus particles are demonstrated frequently in oligodendrocytes by electron microscopy, and JCV antigens may be detected in the brain by immunofluorescence. Given its high sensitivity and specificity, the detection of JCV DNA in spinal fluid by PCR has become the noninvasive assay of choice for diagnosis of PML in the appropriate clinical setting.

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Jul 24, 2016 | Posted by in ORTHOPEDIC | Comments Off on Polyomaviruses

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