Distribution of Nonintegrated DNA from JC Papovavirus in Organs of Patients with Progressive Multifocal Leukoencephalopathy

Autor: Billie L. Padgett, Duard L. Walker, Brian W. Grinnell
Rok vydání: 1983
Předmět:
Zdroj: Journal of Infectious Diseases. 147:669-675
ISSN: 1537-6613
0022-1899
DOI: 10.1093/infdis/147.4.669
Popis: Tissues from 10 patients with progressive multifocal leukoencephalopathy (PML) and 14 patients without PML who were serologically positive for JC papovavirus were examined by molecular hybridization for human polyomavirus DNA sequences. Although viral proteins were not identified by fluorescent antibody methods, viral DNA was found in the kidneys of seven of nine patients with PML by hybridization, at 0.2-10 viral genome copies per cell genome equivalent, compared with 0.6-4 x 103 copies per cell in diseased areas of the brain. Examination of viral DNA from brains and kidneys of patients with PML by blot hybridization yielded no evidence of integration into the host cell genome. In three of the patients with PML, viral DNA was also found in liver, lung, lymph node, and spleen. Two of these patients, with widely disseminated JC virus, were children. In tissues from patients without PML, no evidence of JC virus infection was found, but BK papovavirus DNA was detected in two of 14 kidneys tested. Progressive multifocal leukoencephalopathy (PML) is a chronic demyelinating disease associated with the human polyomavirus JC virus [1]. JC virus appears to be an opportunistic pathogen because PML is generally seen in individuals with depressed immunity. Although the disease is relatively rare, infection is quite common; most adults are serologically positive [2]. Infection is usually acquired early in life and results in viral persistence [3]. Reactivation, accompanied by urinary excretion of JC virus, has been demonstrated in healthy pregnant women [4, 5] and renal transplant recipients [6, 7], but it is not known whether PML occurs after reactivation or after primary infection while immunity is depressed. A knowledge of the distribution of JC virus in the organs of both seropositive normal individuals and patients with PML would help in understanding the pathogenesis of PML and the sites and mechanism of viral persistence. However, methods such as viral isolation and electron microscopy are tedious, insensitive to small amounts of virus, and rely on either identifying recognizable virion structures (electron microscopy) or infectious virions (isolation), which are not always present in persistent infections. Detection of virion-coded antigens, by immunostaining methods, requires that the viral genome be expressed. Many of these problems can be avoided by examining tissues for the viral genome by hybridization methods. These very sensitive techniques also allow for the assessment of the physical state of the
Databáze: OpenAIRE