The effects of measles virus and various strains of SSPE virus on organotypic cultures of nervous tissue
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Subacute sclerosing panencephalitis
Morbillivirus
Measles virus generally produces acute illness. Rarely, however, persistent infection of brain cells occurs, resulting in a chronic and fatal neurological disease, subacute sclerosing panencephalitis (SSPE). Evidence indicates that expression of the measles virus matrix protein is selectively restricted in this persistent infection, but the mechanism underlying this restriction has not been identified. Defective translation of matrix messenger RNA has been described in one SSPE cell line. This report presents evidence that in a different SSPE tissue culture cell line IP-3-Ca, the matrix protein is synthesized but fails to accumulate. A general scheme is proposed to reconcile the different levels at which restriction of matrix protein has been observed.
Subacute sclerosing panencephalitis
Morbillivirus
Matrix (chemical analysis)
Slow virus
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Subacute sclerosing panencephalitis
Morbillivirus
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Summary The presence of five structural proteins of measles virus in brain material obtained at autopsy from four patients with subacute sclerosing panencephalitis (SSPE) was examined by immunofluorescence employing monoclonal antibodies. In addition, the humoral immune response against measles virus antigens in serum and cerebrospinal fluid was analysed by immunoprecipitation in combination with gel electrophoresis, revealing a reduced response mainly to the matrix (M) protein. In none of the brain material were all five structural proteins simultaneously detected. Nucleocapsid protein and phosphoprotein were found in every diseased brain area, whereas haemagglutinin (H) protein was detected in two, fusion (F) protein in three and M protein only in one SSPE case. In two cases, variations in the occurrence of H and F proteins could be observed between regions displaying different degrees of neuropathological changes. No correlation was observed between the humoral immune response and the immunohistological findings. These data support the hypothesis of a restricted synthesis of measles virus proteins, in particular the envelope and M proteins, in SSPE.
Subacute sclerosing panencephalitis
Morbillivirus
Immunofluorescence
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Infection of vascular endothelium plays a central role in the pathogenesis of acute measles virus infection outside the central nervous system (CNS) but has not been described in the human CNS. An ultrastructural survey was made of blood vessels in five cases of subacute sclerosing panencephalitis (SSPE) to determine whether or not infection of cerebral vascular endothelium occurred in this persistent fatal CNS disease caused by measles virus. Morbillivirus nucleo‐capsids were found in a few endothelial cells in three necropsy cases but not in the limited tissue available from two biopsies. In a severe parenchymal lesion in one necropsied case, endothelial cells hybridized in situ with a biotinylated probe specific for the N genomic RNA of measles virus. It is concluded that human cerebral endothelium is susceptible to measles virus infection.
Subacute sclerosing panencephalitis
Morbillivirus
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Canine distemper
Subacute sclerosing panencephalitis
Morbillivirus
Mononegavirales
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Subacute sclerosing panencephalitis
Morbillivirus
Mononegavirales
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The persistence of measles virus in selected areas of the brains of four patients with subacute sclerosing panencephalitis (SSPE) was characterized by immunohistological and biochemical techniques. The five measles virus structural proteins were never simultaneously detectable in any of the brain sections. Nucleocapsid proteins and phosphoproteins were found in every diseased brain area, whereas hemagglutinin protein was detected in two cases, fusion protein was detected in three cases, and matrix protein was detected in only one case. Also, it could be shown that the amounts of measles virus RNA in the brains differed from patient to patient and in the different regions investigated. In all patients, plus-strand RNAs specific for these five viral genes could be detected. However, the amounts of fusion and hemagglutinin mRNAs were low compared with the amounts in lytically infected cells. The presence of particular measles virus RNAs in SSPE-infected brains did not always correlate with mRNA activity. In in vitro translations, the matrix protein was produced in only one case, and the hemagglutinin protein was produced in none. These results indicate that measles virus persistence in SSPE is correlated with different defects of several genes which probably prevent assembly of viral particles in SSPE-infected brain tissue.
Subacute sclerosing panencephalitis
Morbillivirus
Mononegavirales
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Comparative studies between two measles virus strains isolated from patients with subacute sclerosing panencephalitis (SSPE) and a prototype low tissue culture passage Edmonston measles virus are described. Differences were noted in several properties. The findings described in this report suggest that strains of measles virus associated with SSPE have different biological properties and apparently cannot be distinguished from laboratory and field strains of the virus.
Subacute sclerosing panencephalitis
Morbillivirus
Mononegavirales
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Subacute sclerosing panencephalitis
Morbillivirus
Parenchyma
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Subacute sclerosing panencephalitis (SSPE) is a slow infection caused by measles virus in which several years separate recovery from typical acute measles and the development of a slowly progressive neurological disease. We have investigated replication of measles virus in brain tissue obtained after the onset of neurological disease and in the terminal phase. With a hybridization tomographic technique that combines in situ hybridization with macroradioautographic screening of large areas of tissue, we analyzed the spatial and temporal distribution of virus genes in vivo, using region- and strand-specific probes for the nucleocapsid and matrix genes. We show that early in the course of SSPE there is a global repression in the synthesis and expression of the genome. In the final stage of SSPE most infected cells still have depressed levels of plus- and minus-strand viral RNA and contain nucleocapsid protein but lack matrix protein. These findings provide further evidence for a unified view of slow infections of the nervous system, where the general constraints on virus gene expression provide an explanation for persistence of virus in the face of the host's immune response, and the slow evolution of pathological change. In the final phases of SSPE the more specific block in virus replication accounts for the cell-associated state of the virus and the difficulty in virus isolation.
Subacute sclerosing panencephalitis
Morbillivirus
Mononegavirales
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