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.
"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  . Briefly, paraffin sections of endometrial carcinoma were dried at 40 8C overnight, deparaffinized, and rehydrated. "
[Show abstract][Hide abstract] ABSTRACT: To look for an association between the measles virus and endometrial carcinoma, the most frequent cancer of the female genital tract in our area.
Thirty-six of 49 patients with endometrial carcinoma were studied to detect fingerprints of the measles virus. Immunohistochemistry with the avidin-biotin complex method and in situ hybridization were used to demonstrate the association. The clinicopathological correlations were carried out to support a relationship between the virus and the cancer if any was found.
Twenty-six of the 36 cases (72%) of endometrial cancer showed the presence of measles virus antigens in the tumor cells. Sixteen of 21 cases were positive for measles virus RNA by in situ hybridization. Although type I endometrial carcinoma was more positive for viral particles than type II, type II cancer, when allied with the measles virus, was more often associated with the depth of myometrial invasion and with death from tumor.
We demonstrate for the first time a link between endometrial cancer and the presence of viral antigens and RNA of the measles virus, although these findings do not necessarily signify a causal relationship between the cancer and the virus.
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
"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. "
[Show abstract][Hide abstract] ABSTRACT: The quest for an infectious agent that may account for cases of Hodgkin's disease (HD) especially in young adults has proven vain until lately. We have recently reported findings that suggested the presence of measles virus (MV) antigens and MV RNA in the tissues of patients with HD. Support for an association between MV and HD has been provided by recent epidemiological findings relating the occurrence of HD to exposure to measles in pregnancy and the perinatal period. We now present further evidence of this putative association based on immunohistochemical, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridisation studies (ISH) on HD tissues. Biopsies from 82 (54.3%) of our cohort of 154 patients showed a positive immunostain with at least two of the anti-measles antibodies used. Latent membrane protein-1 immunostaining for Epstein-Barr virus was positive in 46 (31.1%) of the patients examined. Reverse transcriptase-PCR and ISH for measles RNA were positive in seven and 10 of 28 patients, respectively. Preliminary clinicopathological associations between MV and HD are noted in this study, but no causal relationship can be claimed at this stage.
British Journal of Cancer 09/2004; 91(3):572-9. DOI:10.1038/sj.bjc.6601900 · 4.84 Impact Factor
"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. "
[Show abstract][Hide abstract] 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.
Journal of General Virology 09/2003; 84(Pt 8):2133-43. DOI:10.1099/vir.0.19091-0 · 3.18 Impact Factor
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