Ultrastructural Studies in the Lytic Phase of Progressive Multifocal Leukoencephalopathy in AIDS Patients
ABSTRACT Brain fragments from eight cases (four autopsies and four biopsies) of patients with acquired immune deficiency syndrome (AIDS) with JC virus (JCV) lytic infections were examined ultrastructurally. Particular efforts were made to look for virions and their subcellular distribution in cells not usually involved by papovavirus infection. The cellular and subcellular distribution of virions was investigated with emphasis on cell types not normally associated with papovavirus infection. The pattern of JCV infection was as follows: 1) oligodendrocytes; nucleus only, 7 cases; cytoplasm only, no cases; 2) astrocytes (normal and "bizarre"); nucleus and cytoplasm, two cases; cytoplasm only, four cases; 3) macrophages; nucleus and cytoplasm, one case; cytoplasm only, four cases; and 4) neurons; nucleus and cytoplasm, two cases; cytoplasm only, three cases. Perivascular, endothelial, ependymal, and microglial cells were never infected. Our ultrastructural data indicate that cell types other than oligodendrocytes can be involved productively by JCV in the lytic phase of progressive multifocal leukoencephalopathy (PML) in AIDS patients. Neuronal cells, especially, can be infected productively by the JCV, and this should be considered in clinical interpretation of cortical symptoms and signs in suspected or proven cases of PML.
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- "In infected oligodendrocytes JCV DNA was not only found in the nucleus but in some cells also within the cytoplasm. Ultrastructural studies have con®rmed the presence of JCVparticles within these cell compartments (Mazlo and Tariska, 1980; Boldorini et al, 1993; von Einsiedel et al, 1993). Surprisingly, using in situ PCR, oligodendrocytes with cytoplasmic staining only were also seen (Figure 4b). "
ABSTRACT: Opportunistic infection of the central nervous system by human polyomavirus JC can cause a devastating disease, progressive multifocal leukoencephalopathy (PML). To gain new neuropathological insights into JC-virus (JCV) infection patterns in PML at the light microscopic level, the highly sensitive indirect in situ polymerase chain reaction (in situ PCR) was employed in up to 15-year old formalin-fixed and paraffin-embedded postmortem brain tissue derived from nine AIDS patients with PML. In situ PCR, in which target DNA is amplified intracellularly and detected by a specific labelled probe in morphologically intact tissue, was compared with conventional in situ hybridization (ISH). Validity was ensured by the inclusion of 13 controls. JCV detection with in situ PCR proved to be highly sensitive since in all nine brain samples the number of positive cells exceeded the ISH results by 2-3-fold. Whereas by routine staining the brain tissue of each individual patient showed regions with severe, mild or no involvement by PML, improved detection of JCV DNA by in situ PCR allowed a regrading into five different degrees of JCV infection. Significant myelin staining was observed, suggesting that cell-to-cell contact may not be the only means of virus spread but that new cells could also be infected by virus released after cell lysis. Furthermore, using in situ PCR hitherto unreported intracellular distribution patterns of JCV DNA in oligodendro- and astrocytes were observed by light microscopy.Journal of NeuroVirology 03/2000; 6(1):61-74. DOI:10.3109/13550280009006383 · 2.60 Impact Factor
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- "Between 1 and 5.9% of cells from transformed B-lymphocyte lines (Atwood et al, 1992), hematopoietic progenitor cell lines and primary tonsilar B-lymphocytes have been infected in vitro with JCV (Monaco et al, 1996). This virus has also been detected in B-lymphocyte-depleted peripheral blood leukocytes of HIV-infected individuals (Dubois et al, 1997) and in brain macrophages of patients with PML (Orenstein et al, 1988; Stoner et al, 1986; Boldorini et al, 1993). Finally, JCV has been found in cell-free plasma of immunosuppressed individuals (Dubois et al, 1997, 1998; Koralnik et al, 1999). "
ABSTRACT: While it has been suggested that JC virus (JCV) migrates in B-lymphocytes from the kidney to the central nervous system where it initiates demyelination, this phase of JCV pathogenesis has not been systematically explored. To determine the peripheral blood cell subpopulation(s) infected with JCV, monocytes, granulocytes, and T and B lymphocytes from HIV-1-infected individuals and uninfected controls were purified by flow cytometry. JCV DNA could be detected by PCR amplification in all of these cell subpopulations. This finding suggests that JCV lacks specificity in its interaction with leukocytes.Journal of NeuroVirology 09/1999; 5(4):430-5. DOI:10.3109/13550289909029484 · 2.60 Impact Factor
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ABSTRACT: Progressive multifocal leukoencephalopathy, a formerly rare disease that chiefly occurred in persons with underlying lymphoma and chronic lymphocytic leukemia, is now seen with increasing frequency in the era of acquired immunodeficiency syndrome. Progressive multifocal leukoencephalopathy is currently estimated to arise in 5% of all human immunodeficiency virus-infected individuals. The clinical features of the disorder in patients with acquired immunodeficiency syndrome do not appear to be significantly different from progressive multifocal leukoencephalopathy occurring in association with other immunosuppressive disorders. Radiographically, the appearance of HIV dementia on magnetic resonance imaging is sometimes confused with that of progressive multifocal leukoencephalopathy. Among the characteristics that are helpful in distinguishing between the two disorders are the presence of focal findings, the rate of disease progression, the specific magnetic resonance imaging attributes, including the location of the lesions, and certain cerebrospinal fluid parameters, including surrogate markers for human immunodeficiency virus dementia and the presence of myelin basic protein. The remarkable increase in the burden of progressive multifocal leukoencephalopathy has provided a vital impetus for its study, particularly with respect to diagnosis and therapy. Establishing an unequivocal diagnosis of progressive multifocal leukoencephalopathy currently requires brain biopsy. The application of polymerase chain reaction for JC virus amplification to cerebrospinal fluid samples suggests that it may provide an alternative means of diagnosis. Recent in vitro studies of cytosine arabinoside and camptothecin suggest that they, or similar agents, may prove useful in the treatment of this illness and well-designed clinical trials are underway.Journal of NeuroVirology 04/1995; 1(1):5-18. DOI:10.3109/13550289509111006 · 2.60 Impact Factor