Chapter 103 : Human Polyomaviruses

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Lymphotropic polyomavirus (LPyV), a nonhuman primate polyomavirus, is classified as a strain of African green monkey polyomavirus. The newly identified putative human polyomaviruses (HPyV) WU polyomavirus (WUPyV), KI polyomavirus (KIPyV), and Merkel cell polyomavirus (MCPyV) have yet to be formally classified. Antemortem direct microscopic examination of tissue is performed less commonly for progressive multifocal leukoencephalopathy (PML) than for polyomavirus-associated nephropathy (PVAN) due to the risks involved in obtaining brain biopsy material. PCR methods can be classified as having either conventional or real-time formats. For JCPyV and BKPyV, two types of serological tests have been described, including hemagglutination inhibition (HAI) and enzyme immunoassays (EIAs) employing either crude antigens or the use of virus-like particles (VLPs). Detection of an antibody response by HAI is based on the capacity of specific antiviral antibodies to inhibit the agglutination of human erythrocytes mediated by the viral structural VP1 proteins of JCPyV and BKPyV. Current approaches to therapy include having optimal highly active antiretroviral therapy (HAART) for HIV-infected patients, with the aim of increasing CD4 cell counts and decreasing the HIV RNA level. The current trend in laboratory testing for PVAN is to monitor levels of the BKPyV in urine and blood and to reduce immunosuppression when viruria or viremia reaches levels that predict progression to disease.

Citation: Buller R. 2011. Human Polyomaviruses, p 1624-1635. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch103

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TaqMan Real-Time PCR Assay
Central Nervous System Diseases
Highly Active Antiretroviral Therapy
Merkel cell polyomavirus
Simian virus 40
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Image of FIGURE 1

MR image showing the brain of a patient with lesions of advanced PML. Lesions are seen bilaterally in frontal lobes and in parieto-occipital subcortical regions. Note that the cortex is spared, with lesions primarily in the white matter, consistent with the pathology of demyelination of white matter tracts (fluid-attenuated inversion recovery T2-weighted MR). Reprinted from ( ) with permission of the publisher.

Citation: Buller R. 2011. Human Polyomaviruses, p 1624-1635. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch103
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Image of FIGURE 2

PVAN pathology. (A) Photomicrograph of a hematoxylin- and eosin-stained renal biopsy specimen showing nuclear inclusion (arrow) in an epithelial cell in a collecting duct (magnification, ×200). (B) Photomicrograph of Papanicolaou-stained decoy cells from the urine of a patient with PVAN demonstrating the typical enlarged basophilic nuclei (magnification, ×400). (C) Electron micrograph of a renal biopsy specimen showing arrays of typical 40 to 45 nm diameter polyomavirus virions (magnification, ×12,000). (D) Photomicrograph of an immunostained renal biopsy specimen showing staining of homogenous type 1 nuclear inclusions (arrows) in epithelial cells of distal tubes. (Images courtesy of Helen Liapis, Washington University.)

Citation: Buller R. 2011. Human Polyomaviruses, p 1624-1635. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch103
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Image of FIGURE 3

PML pathology. (A) Gross section of the brain from a patient with PML demonstrating asymmetric focal patches of involvement mostly confined to the white matter. (B) Photomicrograph of a hematoxylin- and eosin-stained section of the brain from a patient with PML showing “plum-colored” oligodendroglial nuclei (arrows), some with marginated chromatin and inclusions. Infected oligodendrocytes are markedly enlarged compared to more normal sized oligodendroglia (arrowheads) (magnification, 3400). (C) Electron micrograph of the brain from a patient with PML showing the “stick and ball” or “spaghetti and meatballs” (arrows) appearance of JCPyV in an oligodendrocyte (magnification, 358,000). (D) Photomicrograph of an immunostained brain section demonstrating JCPyV proteins in enlarged immunoreactive oligodendroglial nuclei (arrowhead) but little involvement of atypical astrocytes (arrow) (magnification, 3600). (E) Photomicrograph of in situ hybridization using a labeled JCPyV probe showing a positive signal in oligodendrocytes (arrowheads) and an atypical labeled astrocyte (arrow) (magnification, 31,000). (Images courtesy of Robert Schmidt, Washington University.)

Citation: Buller R. 2011. Human Polyomaviruses, p 1624-1635. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch103
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Diseases associated with HPV

PBMC, peripheral blood mononuclear cells.

Citation: Buller R. 2011. Human Polyomaviruses, p 1624-1635. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch103
Generic image for table

Commercial nucleic acid amplification products for the detection of JCPyV and BKPyV

RUO, research use only; MGB, minor groove binder; ASR, analyte-specific reagent.

Citation: Buller R. 2011. Human Polyomaviruses, p 1624-1635. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch103

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