Chapter 105 : Human Polyomaviruses

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Novel human polyomaviruses (HPyVs) continue to be reported, with a total of 12 HPyVs now reported in the literature. The original HPyVs, BK polyomoavirus (BKPyV) and JC polyomavirus (JCPyV), are important human pathogens, causing infections in immunocompromised patients. Merkel cell polyomavirus (MCPyV) appears to be the causative agent of some forms of Merkel cell carcinoma, a rare form of skin cancer. Another novel HPyV has been linked to trichodysplasia spinulosa, an uncommon skin disease seen in immunocompromised patients. The remaining novel HPyVs have been isolated from respiratory, stool, and skin samples and have not yet been linked to any specific human diseases. Clinical microbiology laboratories are therefore generally not concerned with testing for most of the newly identified HPyVs. Rather, it is molecular-based testing for BKPyV and JCPyV that is of greatest importance. While there are still no FDA-approved assays for these viruses, there are several analyte-specific and research use only reagents available. Testing for BKPyV is performed to monitor kidney transplant recipients for the development of polyomavirus-associated nephropathy and less commonly when searching for a cause of hemorrhagic cystitis. Detection of JCPyV is undertaken to make a diagnosis of progressive multifocal leukoencephalopathy, a disease of the central nervous system that occurs in patients with certain types of underlying immune dysfunction. Looking to the future, it is likely that more HPyVs will be identified. It will be interesting to see if any are linked to specific diseases or if they are simply part of what is being recognized as the human virome.

Citation: Buller R. 2015. Human Polyomaviruses, p 1803-1817. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch105
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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 white matter, consistent with the pathology of demyelination of white matter tracts (fluid-attenuated inversion recovery T2-weighted MR). Reprinted with permission of Lippincott Williams & Wilkins from . doi:10.1128/9781555817381.ch105.f1

Citation: Buller R. 2015. Human Polyomaviruses, p 1803-1817. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch105
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Image of FIGURE 2

PVAN pathology. (A) Photomicrograph of hematoxylin and eosin-stained renal biopsy specimen showing nuclear inclusion (arrow) in epithelial cell in 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. doi:10.1128/9781555817381.ch105.f2

Citation: Buller R. 2015. Human Polyomaviruses, p 1803-1817. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch105
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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 hematoxylin and eosin-stained section of 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, ×400). (C) Electron micrograph of brain from a patient with PML showing the “stick and ball” or “spaghetti and meatballs” (arrows) appearance of JCPyV in an oligodendrocyte (magnification, ×58,000). (D) Photomicrograph of an immunostained brain section demonstrating JCPyV proteins in enlarged immunoreactive oligodendroglial nuclei (arrowhead) but little involvement of atypical astrocytes (arrow) (magnification, ×600). (E) Photomicrograph of ISH using a labeled JCPyV probe showing a positive signal in oligodendrocytes (arrowheads) and an atypical labeled astrocyte (arrow) (magnification, ×1,000). Images courtesy of Robert Schmidt, Washington University. doi:10.1128/9781555817381.ch105.f3

Citation: Buller R. 2015. Human Polyomaviruses, p 1803-1817. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch105
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Diseases associated with HPyV

Citation: Buller R. 2015. Human Polyomaviruses, p 1803-1817. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch105
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Commercial nucleic acid amplification products available in the United States for the detection of JCPyV and BKPyV

Citation: Buller R. 2015. Human Polyomaviruses, p 1803-1817. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch105

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