Accumulated measles virus mutations in a case of subacute sclerosing panencephalitis: Interrupted matrix protein reading frame and transcription alteration

Roberto Cattaneo, Anita Schmid, Gabriela Rebmann, Knut Baczko, Volker Ter Meulen, William J. Bellini, Shmuel Rozenblatt, Martin A. Billeter

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Abstract

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 different 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.

Original languageEnglish (US)
Pages (from-to)97-107
Number of pages11
JournalVirology
Volume154
Issue number1
DOIs
StatePublished - Oct 15 1986

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ASJC Scopus subject areas

  • Virology

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