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  • 1995-1999  (2)
  • 1830-1839
  • 1995  (2)
  • Canine distemper virus  (1)
  • Pneumonitis  (1)
  • 1
    ISSN: 1432-0533
    Keywords: Canine distemper virus ; Oligodendrocytes ; Myelin gene expression ; Demyelination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Canine distemper virus (CDV) induces oligodendroglial degeneration and multifocal demyelination in the central nervous system. The mechanism of oligodendrocyte degeneration is not understood but it has been shown that there is a restricted infection of these cells without viral protein production. Using a combination of immunocytochemistry and in situ hybridization we were able to demonstrate the transcription of the entire virus genome throughout the whole observation period (7–35 days after infection) in oligodendrocytes in CDV-infected brain cell cultures. Therefore, the lack of viral protein and particle production can not be explained on the basis of a defective viral transcription. The present study also shows that a restricted infection of oligodendrocytes with CDV down-regulates the transcription of the major myelin genes coding for proteolipid protein, myelin basic protein (MBP) and myelin-associated glycoprotein in a very similar way. Using densitometry for in situ hybridization products of MBP in populations of normal and infected oligodendrocytes, an effect could be observed long before morphological changes were detectable. The present results strongly suggest that demyelination in distemper is induced by a restricted CDV infection of oligodendrocytes which down-regulates the expression of a variety of cellular genes, in particular those coding for myelin proteins. Consequently, the infected cells are no longer able to synthesize all the membrane compounds which are necessary for maintaining their structural integrity.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1831
    Keywords: Cytomegalovirus (CMV) ; Pneumonitis ; Graft-versus-host disease (GvHD) ; Bone marrow transplantation (BMT)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a retrospective analysis lung biopsy specimens obtained postmortem from 30 consecutive allogeneic bone marrow transplant recipients who had died of either interstitial pneumonitis (IP; 18/30 patients) or various other causes (12/30 patients) were studied for the local presence of human cytomegalovirus (HCMV) by culture, in situ hybridization, polymerase chain reaction (PCR) and immunohistochemistry for HCMV proteins. All patients suffering from IP were found to be HCMV positive in the lung biopsy. PCR revealed the highest sensitivity for HCMV detection in lung biopsies, but in 15/18 PCR-positive samples local HCMV infection could be confirmed by at least one additional technique. All the lung biopsies obtained from the 12 patients without IP were negative for HCMV by all techniques applied, except one with a weak HCMV-DNA signal in the PCR assay. The severity of the clinical, as well as histological and immunohistological alterations in the lung did not correlate with the amount of HCMV-DNA or the number of HCMV-positive cells detected in the biopsy. An increase of HLA-class II antigen and of ICAM-1 expression on the alveolar epithelium, as well as presence of activated CD8+ or CD4+ lymphocytes infiltrating only HCMV-positive lung biopsies revealed T cell-mediated immune reactions to be involved in the pathogenesis of IP. Since all analyzed patients presented with severe acute or extensive chronic graft-versus-host disease (GvHD), but only those with pulmonary HCMV infection developed IP, dissemination of HCMV appears to be the primary requirement for the initiation of IP. GvHD, however, may interfere with normal control of subsequent antiviral immune responses and, thus, provoke the immunopathology of IP.
    Type of Medium: Electronic Resource
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