Absence of measles virus receptor (CD46) in lesions of subacute sclerosing panencephalitis brains

Institut für Virologie und Immunobiologie, Universität Würzburg, Germany.
Acta Neuropathologica (Impact Factor: 10.76). 12/1997; 94(5):444-9. DOI: 10.1007/s004010050731
Source: PubMed


In this study we investigated pathological changes of the expression of the measles virus (MV) receptor, CD46, in subacute sclerosing panencephalitis (SSPE) brains. We analyzed CD46 expression in lesions of brain specimens from five SSPE patients in comparison to uninfected regions of the same brains and to normal human brains. The correlation between CD46 and MV infection, in individual cells in SSPE brains, was analyzed by double-staining procedures using monoclonal antibodies (mAbs) and in situ hybridization to detect MV-specific mRNAs. We found that CD46 was expressed at relatively low levels by neurons and astrocytes in normal brains in comparison to neuroblastoma and astrocytoma cell lines. Within heavily infected (MV-positive) brain lesions of all five SSPE cases, CD46 was either not detected or was expressed to a lesser degree by neural cells, irrespective of whether MV antigens were detectable or not. In contrast, normal levels of CD46 were found in SSPE brain tissue distant from the lesion. Using in situ hybridization, mRNAs of both MV nucleocapsid and MV hemagglutinin (MV-H) were detected in all SSPE lesions, while no or only small amounts of MV-H protein were detected. MV-infected neurons were never found to express CD46. Although a strict correlation between levels of the MV-H protein and the absence CD46 could not be seen, these findings suggest that the CD46 expression is reduced by the MV infection in lesions of SSPE brains.

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    • "In situ hybridization (ISH) was performed on 21 of the 36 cases to identify the RNA fragments of the MV in tumor tissue and in the surrounding non-neoplastic endometrial mucosa. For this purpose we used the method of Ogata et al. with minor modifications as described [11] [14]. Briefly, paraffin sections of endometrial carcinoma were dried at 40 8C overnight, deparaffinized, and rehydrated. "
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    European journal of obstetrics, gynecology, and reproductive biology 10/2009; 147(2):206-9. DOI:10.1016/j.ejogrb.2009.08.008 · 1.70 Impact Factor
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    • "In situ hybridisation was carried out according to the method of Ogata et al (1997) with certain modifications. Paraffin sections were deparaffinised, rehydrated and treated by microwave in the presence of 10 mM MgCl 2 buffer (pH 6) for 5 min at 750 W. Sections were allowed to cool for 20 min, and then digested with 20 mg ml À1 proteinase K for 10 min at 371C. "
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    British Journal of Cancer 09/2004; 91(3):572-9. DOI:10.1038/sj.bjc.6601900 · 4.84 Impact Factor
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    • "CD46 isoforms with cytoplasmic tail 2 were isolated from a brain of SSPE, expressed and found to interact with H protein (Buchholz et al., 1996). The disappearance of CD46 in SSPE lesions in the brain, which has also been reported by Ogata et al. (1997), can be explained by the H protein-mediated downregulation of the CD46 molecule. However, CD46 was not used as an entry receptor by the three strains of SSPE used in our study. "
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    ABSTRACT: The vaccine or Vero cell-adapted strains of measles virus (MV) have been reported to use CD46 as a cell entry receptor, while lymphotropic MVs preferentially use the signalling lymphocyte activation molecule (SLAM or CD150). In contrast to the virus obtained from patients with acute measles, little is known about the receptor that is used by defective variants of MV isolated from patients with subacute sclerosing panencephalitis (SSPE). The receptor-binding properties of SSPE strains of MV were analysed using vesicular stomatitis virus pseudotypes expressing the envelope glycoproteins of SSPE strains of MV. Such pseudotype viruses could use SLAM but not CD46 for entry. The pseudotype viruses with SSPE envelope glycoproteins could enter Vero cells, which do not express SLAM. In addition, their entry was not blocked by the monoclonal antibody to CD46, pointing to another entry receptor for SSPE strains on Vero cells. Furthermore, the unknown receptor(s), distinct from SLAM and CD46, may be present on cell lines derived from lymphoid and neural cells. Biochemical characterization of the receptor present on Vero cells and SK-N-SH neuroblastoma cells was consistent with a glycoprotein. Identification of additional entry receptors for MV will provide new insights into the mechanism of spread of MV in the central nervous system and possible reasons for differences between MVs isolated from patients with acute measles and SSPE.
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