Altered transcription of a defective measles virus genome derived from a diseased human brain

Abstract

Measles virus (MV) is a negative strand RNA virus which usually causes acute disease, but in rare cases its persistence in the human brain induces the lethal disease subacute sclerosing panencephalitis (SSPE). The transcription of MV and of a defective MV derived from autopsy material of a SSPE case was studied in cultured cells. In the lytic infection the levels of the MV mRNAs decreased progressively with the distance of the six cognate genes from the 3' end of the genome, reflecting transcriptional attenuation at every gene junction. Transcripts covering two or three adjacent genes accounted for up to 20% of single gene transcripts; incidentally the MV intergenic transcription signals were found to be less conserved than the analogous signals of other negative strand RNA viruses. Although the analysed SSPE-derived defective MV showed a localized transcription defect at the phosphoprotein--matrix gene junction (substitution of the mRNAs by readthrough transcripts), the corresponding intergenic 'consensus' sequence and the surrounding nucleotides were not altered. This implies that factor(s) involved in the transcription of this defective SSPE virus fail to recognize this particular signal sequence, a constellation which in this and other cases might be causally related to the development of MV persistence.