Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis (original) (raw)
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Journal of General Virology, 1986
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. 0000-7226 © 1986 SGM Downloaded from www.microbiologyresearch.org by IP: 54.160.90.203
Infection, Genetics and Evolution, 2013
Measles virus (MV) strains derived from patients with subacute sclerosing panencephalitis (SSPE), SSPE strains, possess numerous mutations when compared to viruses belonging to the same genotype and circulating in similar time period. Although many SSPE strains have been extensively characterized, none of them belongs to D4 genotype which currently predominates in Europe where it has caused a number of recent outbreaks/epidemics. We sequenced an MV derived from a patient with long-term SSPE; the virus was named MVs/Zagreb.-CRO/30.06[D4] (SSPE). Initial genetic analysis showed that it belongs to D4 genotype. The sequences of genes encoding matrix and fusion proteins indicate premature protein terminations. Putative hemagglutin (H) protein is lengthened for 20 amino acids, which is the longest H protein elongation so far found in SSPE viruses. Nucleotides 1421 A, 1422 G, 1507 C and 1542 C in nucleoprotein gene open reading frame seem to be specific for this D4 strain, differentiating it from other D4 non-SSPE strains. Besides, a unique mutation at position 543 of H protein was found, histidine instead of tyrosine. As persistent MV infections are initially established by ''normal'' wild-type MV strains, the presented comparative analyses describe alterations that could be involved in the maintenance of persistent infection, disease development and progression.
Journal of Medical Virology, 2011
Measles virus strains from two subacute sclerosing panencephalitis (SSPE) cases diagnosed in 1977 (Laine strain) and in 2007 (Hoedts strain) were studied. Phylogenetic analysis based on C-terminal part of the nucleoprotein and the entire H gene showed that Hoedts strain, circulating in France presumably in the 1980s, belonged to genotype C2. However, Laine strain, suspected to have circulated between 1940s and 1960s, could not be assigned to any known measles virus genotypes. Sequences analysis of the Laine strain suggested that it originated from a measles virus that may have circulating at the same period as the Edmonston strain. The analysis of the whole genome of both SSPE strains revealed biased hypermutations in M, F, and H gene. Some of these mutations like the L165P found in the M protein sequence of the Laine strain, the amino acid position 94, where a mutation M94V was found in the F protein sequence of the Hoedts strain are known to play an important role in the glycoprotein interaction and to impair the ability of measles virus strain to produce cell-free infectious viral particles.This is the first study on molecular characterization of the entire coding region of measles virus isolated from SSPE cases in France.
Journal of Virology, 1988
A measles virus (MV) genome originally derived from brain cells of a subacute sclerosing panencephalitis patient expressed in IP-3-Ca cells an unstable MV matrix protein and was unable to produce virus particles. Transfection of this MV genome into other cell lines did not relieve these defects, showing that they are ultimately encoded by viral mutations. However, these defects were partially relieved in a weakly infectious virus which emerged from IP-3-Ca cells and which produced a matrix protein of intermediate stability. The sequences of several cDNAs related to the unstable and intermediately stable matrix proteins showed many differences in comparison with a stable matrix protein sequence and even appreciable heterogeneity among themselves. Nevertheless, partial restoration of matrix protein stability coul be ascribed to a single additional amino acid change. From an examination of additional genes, we estimated that, on average, each MV genome in IP-3-Ca cells differs from the others in 30 to 40 of its 16,000 bases. The role of extreme variability of RNA virus genomes in persistent viral infections is discussed in the context of the pathogenesis of subacute sclerosing panencephalitis and of other human diseases of suspected viral etiology.
Virology, 1986
Subacute sclerosing panencephalitis (SSPE) is a fatal disease affecting the human central nervous system several years after acute measles infection. Measles virus (MV) genomes replicating in SSPE brains do not give rise to budding particles and present various defects in gene expression, mostly concerning the matrix (M) protein. For one SSPE case (K), shown previously to be devoid of M protein expression, we examined here in detail the features involved in this defect. In the brain of patient K the normal, monocistronic MV M mRNA was completely substituted by a bicistronic RNA containing the coding sequence of the preceding phosphoprotein (P) gene in addition to the M coding sequence. Analysis of the P-M intercistronic region by direct cDNA sequencing showed that the consensus sequence at this RNA processing site was unaltered but revealed several distant point mutations. cDNA cloning and sequencing of the entire M coding region established that one of the point mutations leads to a stop codon at triplet 12 of the M reading frame. It is unknown whether this defect, explaining by itself the lack of M protein, is related also to the block of M mRNA formation. In addition we note that as much as 1% of the nucleotides differed between two overlapping clones from the same brain. This high sequence variability could possibly account for the diversity of defects observed in MV gene expression in SSPE brains and may be a general phenomenon associated with RNA virus persistence.
Virology, 1992
Our recent extensive analysis of three cases of subacute sclerosing panencephalitis (SSPE) revealed intriguing genetic defects in the persisting measles virus (MV): the fusion (F) genes encoded truncated cytoplasmic F protein domains (Cattaneo et al., Virology 173, 415-425, 1989). Now this MV genomic region has been investigated in eight additional SSPE cases by PCR amplification, replacement cloning into a vector containing the F gene of a lytic MV, in vitro expression, and sequencing. In all cases at least part of the clones showed mutations leading to F protein truncations, elongation, or nonconservative amino acid replacements. It is proposed that alteration of the F protein cytoplasmic domain may play a critical role in the development of SSPE.
Patterson et al.Measles.M mutation.SSPE.Virology.
Subacute sclerosing panencephalitis (SSPE) is a progressive degenerative disease of the brain uniformly leading to death. Although caused by measles virus (MV), the virus recovered from patients with SSPE differs from wild-type MV; biologically SSPE virus is defective and its genome displays a variety of mutations among which biased replacements of many uridine by cytidine resides primarily in the matrix (M) gene. To address the question of whether the SSPE MVs with M mutations are passive in that they are not infectious, cannot spread within the CNS, and basically represent an end-stage result of a progressive infection or alternatively SSPE viruses are infectious, and their mutations enable them to persist and thereby cause a prolonged neurodegenerative disease, we utilized reverse genetics to generate an infectious virus in which the M gene of MV was replaced with the M gene of Biken strain SSPE MV and inoculated the recombinant virus into transgenic mice bearing the MV receptor. Our results indicate that despite biased hypermutations in the M gene, the virus is infectious in vivo and produces a protracted progressive infection with death occurring as long as 30 to 50 days after that caused by MV. In primary neuron cultures, the mutated M protein is not essential for MV replication, prevents colocalization of the viral N with membrane glycoproteins, and is associated with accumulation of nucleocapsids in cells' cytoplasm and nucleus.