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: 9.73). 12/1997; 94(5):444-9. DOI: 10.1007/s004010050731
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Viral infections of the central nervous system(CNS) mostly represent clinically important, often life-threatening complications of systemic viral infections. After acute measles, CNS complications may occur early (acute postinfectious measles encephalitis, APME) or after years of viral persistence (subacute sclerosing panencephalitis, SSPE). In spite of a presumably functional cell-mediated immunity and high antiviral antibody titers, an immunological control of the CNS infection is not achieved in patients suffering from SSPE. There is still no specific therapy for acute complications and persistent MV infections of the CNS. Hamsters, rats, and (genetically unmodified and modified) mice have been used as model systems to study mechanisms of MV-induced CNS infections. Functional CD4+ and CD8+ T cells together with IFN-gamma are required to overcome the infection. With the help of recombinant measles viruses and mice expressing endogenous or transgenic receptors, interesting aspects such as receptor-dependent viral spread and viral determinants of virulence have been investigated. However, many questions concerning the lack of efficient immune control in the CNS are still open. Recent research opened new perspectives using specific antivirals such as short interfering RNA (siRNA) or small molecule inhibitors. Inspite of obvious hurdles, these treatments are the most promising approaches to future therapies.
    Medical Microbiology and Immunology 04/2010; 199(3):261-71. · 3.55 Impact Factor
  • Source
    [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. · 1.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Subacute sclerosing panencephalitis (SSPE) is a fatal sequela associated with measles and is caused by persistent infection of the brain with measles virus (MV). The SI strain was isolated in 1976 from a patient with SSPE and shows neurovirulence in animals. Genome nucleotide sequence analyses showed that the SI strain genome possesses typical genome alterations for SSPE-derived strains, namely, accumulated amino acid substitutions in the M protein and cytoplasmic tail truncation of the F protein. Through the establishment of an efficient reverse genetics system, a recombinant SI strain expressing a green fluorescent protein (rSI-AcGFP) was generated. The infection of various cell types with rSI-AcGFP was evaluated by fluorescence microscopy. rSI-AcGFP exhibited limited syncytium-forming activity and spread poorly in cells. Analyses using a recombinant MV possessing a chimeric genome between those of the SI strain and a wild-type MV strain indicated that the membrane-associated protein genes (M, F, and H) were responsible for the altered growth phenotype of the SI strain. Functional analyses of viral glycoproteins showed that the F protein of the SI strain exhibited reduced fusion activity because of an E300G substitution and that the H protein of the SI strain used CD46 efficiently but used the original MV receptors on immune and epithelial cells poorly because of L482F, S546G, and F555L substitutions. The data obtained in the present study provide a new platform for analyses of SSPE-derived strains as well as a clear example of an SSPE-derived strain that exhibits altered receptor specificity and limited fusion activity.
    Journal of Virology 09/2011; 85(22):11871-82. · 5.08 Impact Factor