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Article

History and current concepts in the pathogenesis of PML

Eugene O. Major, PhD
Cleveland Clinic Journal of Medicine November 2011, 78 (11 suppl 2) S3-S7; DOI: https://doi.org/10.3949/ccjm.78.s2.02
Eugene O. Major
Chief, Laboratory of Molecular Medicine and Neuroscience, AIDS Coordinator, Intramural Program, National Institute of Neurological Disorders and Stroke, Bethesda, MD
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  • For correspondence: majorg@ninds.nih.gov
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ABSTRACT

The JC virus (JCV), first described in 1971, is responsible for initiation of progressive multifocal leukoencephalopathy (PML), a disease characterized by demyelinating plaques and a classic triad of symptoms consisting of cognitive impairment, visual deficits, and motor dysfunction. To establish a diagnosis of PML, evidence of the presence of JCV DNA in pathologic tissue is necessary. The host range for productive infection of JCV is controlled by factors in the cell nucleus that bind to the viral promoter, initiating transcription of mRNA for the coordinated synthesis of viral proteins. Oligodendrocytes, astrocytes, and CD34+ and CD19+ cells of the immune system have the necessary binding proteins in sufficient concentration to allow lytic infection to occur. A strong link between JCV infection in cells of the immune system and cells of the nervous system points to the importance of the tissue origin of JCV latency, the bone marrow that harbors CD34+ cells. The emergence of PML in patients treated with natalizumab and other immune-altering agents supports this observation and provides new insights into the pathogenic mechanisms of JCV infection.

Footnotes

  • Dr. Major reported that he has no financial relationships that pose a potential conflict of interest with this article.

  • © 2011 The Cleveland Clinic Foundation. All Rights Reserved.
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Cleveland Clinic Journal of Medicine: 78 (11 suppl 2)
Cleveland Clinic Journal of Medicine
Vol. 78, Issue 11 suppl 2
1 Nov 2011
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History and current concepts in the pathogenesis of PML
Eugene O. Major
Cleveland Clinic Journal of Medicine Nov 2011, 78 (11 suppl 2) S3-S7; DOI: 10.3949/ccjm.78.s2.02

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History and current concepts in the pathogenesis of PML
Eugene O. Major
Cleveland Clinic Journal of Medicine Nov 2011, 78 (11 suppl 2) S3-S7; DOI: 10.3949/ccjm.78.s2.02
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