Molecular analysis of structural protein genes of the Yamagata-1 strain of defective subacute sclerosing panencephalitis virus. III. Nucleotide sequence of the hemagglutinin gene

The full-length cDNA corresponding to the mRNA for the hemagglutinin (H) protein of the Yamagata-1 strain of the subacute sclerosing panencephalitis (SSPE) virus was cloned and the nucleotide sequence was determined. The mRNA corresponding to the H protein was composed of 1952 nucleotides and contained a single large open reading frame, which encoded 620 amino acids with a predicted molecular weight of 69,723. This cDNA clone expressed the H protein in Cos 7 cells, and the transfected cells showed hemadsorption. The nucleotide and amino-acid sequence homology with the Edmonston strain of MV were 98.0% and 96.6%, respectively. The deduced amino acid sequence had a single hydrophobic domain near the N-terminus that was long enough to serve as an anchor in the membrane. Five potential glycosylation sites were found on the H protein at identical positions as in the H protein of MV. Cysteine and proline were located at almost identical positions as those of the H protein of MV. In addition, monoclonal antibody study revealed that three epitopes, including the domains that were involved in the biological activities of the H protein of MV, were conserved on the Yamagata-1 strain. These results suggested that the H protein of the Yamagata-1 strain of defective SSPE virus is structurally and functionally similar to that of the Edmonston strain of MV.     

Molecular analysis of structural protein genes of the yamagata-1 strain of defective subacute sclerosing panencephalitis virus. II. Nucleotide sequence of a cDNA corresponding to the P plus M dicistronic mRNA

The nucleotide sequence of a cloned cDNA corresponding to the P+M dicistronic mRNA of a subacute sclerosing panencephalitis (SSPE) virus was determined and compared with data of measles virus (MV). The dicistronic mRNA of the SSPE virus consisted of the 3 proximal 626 nucleotides of P mRNA, intercistronic trinucleotides, a full length of M mRNA, and 75 poly A nucleotides. The part encoding the P protein had a high homology to MV, except at the noncoding region. The terminating consensus sequence of the P gene and the intercistronic trinucleotides of the SSPE virus were CTAC(A)₆ and CCT; in MV they are TTAT(A)₆ and CTT, respectively. In the M gene, the starting consensus sequence was exactly the same as MV, but at the 5 proximal end, one third of this gene was different: The first ATG codon of the MV M gene signaling opening of the reading frame was changed to ACG in the SSPE virus and one long open reading frame started from the third ATG codon. The stop codon (TAG) of the MV M gene was also changed to CAG in the SSPE virus. Thus, the deduced SSPE-virus M protein lacked 50 amino acids at the amino terminal and had 15 extra amino acids at the carboxyl end when compared with the MV M protein.     

Isolation and characterisation of a defective measles virus from a subacute sclerosing panencephalitis patient.

A cytopathic measles virus was isolated from a brain biopsy of a subacute sclerosing panencephalitis (SSPE) patient. The agent could be transferred to Vero cells by cocultivation, but the infectivity always remained cell-associated -ie, a defective virus infection. The cell-associated nature of the virus was retained through 25 passages in Vero cells. Intracerebral inoculation of hamsters (2-6 days old) with the cocultured Vero cells gave rise to 100% mortality in 5-7 days. The virus retained its cell-associated nature after passage in hamsters. Electron microscopy of the brain and Vero cocultures showed the presence of virus-like ribonucleoparticles mainly in the nucleus. The presence of viral antigens in the nucleus, cytoplasm, and on the plasma membranes was confirmed by immunofluorescence. Using a combination of immunological and biochemical techniques, it was shown that all the viral proteins were synthesized with the exception of the haemagglutinin. Inclusion of the fusion inhibitor SV4814 (CBZ-D phenylalanine-L-phenylalanine-L-arginine-NO2) in the culture medium led to the elimination of the SSPE infection.     

Diagnostic dilemmas in fulminant subacute sclerosing panencephalitis (SSPE)

This report describes an eleven-year-old boy with atypical features of subacute sclerosing panencephalitis (SSPE), a rare complication of measles. He had only visual symptoms for 2 months followed by rapid neurological worsening to a vegetative state in 10 days. A diagnosis of SSPE was made based on the history of measles, characteristic ocular findings, compatible magnetic resonance imaging and electroencephalographic changes, and elevated ratio of cerebrospinal fluid to serum anti-measles antibody titers     

The distribution of Alzheimer's neurofibrillary tangles and gliosis in chronic subacute sclerosing panencephalitis

Summary In two cases of clinically verified chronic subacute sclerosing panencephalitis (case 1, male, 15 years with a 9-year history; case 2, male, 20 years with a 9-year history) numerous Alzheimer's tangles (AT) were identified throughout the cerebral cortex (containing paired helical filament on electron microsopical examination). The brains were severel atrophic with hydrocephalus ex vacuo, occasional scattered microglial nodules, scant perivascular inflammatory infiltrates and demyelination. Only in case 1 were a few atypical intranuclear inclusion bodies noted. In the six-layered neocortex, a distinct distribution pattern of AT was observed; these lesions were mainly seen in laminae II, III and V (laminar distribution). The glial fibrillary acidic protein stain displayed extensive laminar gliosis mainly of the layers I, IIa, IV and VI; layers III and V, largely occupied by the AT, remained conspicuously spared from gliosis (especially the lamina III). Gliosis was prevalent in the white matter which was atrophic and shrunk. In the hippocampus, the AT involved many pyramidal neurons and, in this layer gliosis was lighter than in the surrounding white matter. In case 2, AT were present in the nucleus of Meynert, hypothalamus and in rapha centralis of the upper brain stem. Overall, the distribution of AT resembled that seen in Alzheimer's disease and aging; however, the senile plaques, vascular amyloidosis and granulovacuolar change were totally absent in both cases.     

HLA antigens in subacute sclerosing panencephalitis patients in Israel

HLA Class I antigens were determined in the 49 subacute sclerosing panencephalitis (SSPE) patients. In analyzing the Arabs and the Jews separately, there is a decrease in HLA-A2 in the Jewish patients (X2 = 3.96; P less than 0.05), a significant increase in the HLA-A29 in the Arab SSPE patients (X2 = 6.29; P less than 0.02), and a slight, insignificant increase of HLA-A29 in the Jewish patients. The present study supports previous findings of Kurent's and needs following studies in larger groups of Arab SSPE patients.     

The treatment of subacute sclerosing panencephalitis with interferon: a case report

Summary A child with subacute sclerosing panencephalitis (SSPE) received intraventricular alpha interferon (IFN) as experimental treatment. The course was monitored by colleagues in pediatric neurology, neuro-opthalmology and clinical psychology, also by monthly EEGS and brain CT scans. Two courses of IFN were administered. During the first course, improvement occurred nearly to the premorbid level of function. About 1 month after this trial was stopped, a severe recrudescence rapidly produced a thalamic state. A second trial of IFN resulted in less improvement. When the brain CT showed severe degeneration, the second trial was stopped. Intraventricular administration of alpha IFN was well tolerated in both courses of therapy. Alpha IFN has promise in the treatment of SSPE but the optimal dosage and duration of treatment are undetermined.     

Signaling lymphocyte activating molecule (SLAM) expression in subacute sclerosing panencephalitis

Signaling lymphocyte activating molecule (SLAM) is a receptor for measles virus which also has immunomodulatory activity. We analyzed SLAM expression in mononuclear cells (MNC) of patients with SSPE (n=7) and control subjects (n=7) from the same population. Native 10% PAGE analysis in cell and brain tissue extracts followed by Western blotting using monoclonal anti-human SLAM showed four types of bands. Differences in the type and amount of SLAM expression were observed between SSPE and control cases. Lymphocytes of SSPE patients showed two types of SLAM bands in comparison to only one in control lymphocytes. Stimulation of cells with lipopolysaccharide (80 u/ml) and concanavalin A (1 microg/ml) in vitro led to the appearance of a second isoform in both groups. Brain homogenates of SSPE patients (n=2) displayed all four types of SLAM isoforms at significantly higher levels than those of control brains (n=2). Our results show native PAGE enables the detection of all SLAM isotypes. The expression of SLAM is increased in lymphocytes, monocytes, and brain tissues of SSPE patients.     

The Origin of Myoclonus and Periodic Synchronous Discharges in Subacute Sclerosing Panencephalitis

We report here a case of a patient with subacute sclerosing panencephalitis (SSPE) and we have analyzed periodic events using dipole tracing methods to clarify the origin of periodic synchronous discharges and myoclonus. Both source generators were located in the subcortical part of the cerebrum, an area adjacent to the thalamus. Although the pathophysiology of periodic events in SSPE has been controversial, dipole tracing methods may contribute to clarify the origin of periodic events in SSPE.     

Intrathecal interferon in subacute sclerosing panencephalitis

Three patients at Stage II of subacute sclerosing panencephalitis (SSPE) were treated with semipurified alpha-interferon (IFN) using different combinations of intrathecal and intravenous routes: 1 x 10(6) IU of alpha-IFN were given every other day up to a total of 15 x 10(6) IU. Transient improvement of neurological symptoms and electroencephalogram were noted in all 3, while cognitive function slightly improved in 2 of them. Clinical benefits gradually disappeared 2 to 6 months after cessation of IFN. Intrathecal antibody production did not change substantially, but CSF Leu 3a/Leu 2a ratio appeared to increase. No significant side effects were observed, except for a mild meningeal inflammatory reaction after each intrathecal administration of IFN.