The Matrix Gene Expression of Subacute Sclerosing Panencephalitis (SSPE) Virus (Osaka‐1 Strain): A Comparison of Two Sibling Viruses Isolated from Different Lobes of an SSPE Brain

Abstract

The Fr/V and Oc/V sibling viruses of the Osaka-1 strain of the subacute sclerosing panencephalitis (SSPE) virus were defective in cell-free virus production. By radioimmunoprecipitation assay, the matrix (M) protein was not detected in cells persistently infected with the Osaka-1 strain. This undetectable expression was consistent with the selective reduction of antibody response to the M protein in the patient from whom the Osaka-1 strain was isolated. The sequence of the M gene, however, predicted that the protein could be synthesized because the translational start and stop codons for the protein were not altered. Northern blot hybridization demonstrated the selective defect of the monocistronic mRNAs for the M protein and the phosphoprotein (P) together with the dominant presence of the P-M bicistronic mRNA. This absence of the M mRNA was further confirmed by primer extension analysis. Therefore, the undetectable expression of the M protein in the infected cells was proved to be caused by a transcriptional defect. The two sibling viruses, isolated from remote portions of an SSPE brain, were indistinguishable in their viral characters, including the M gene sequences, which indicates the possibility of clonal expansion of the strain in the brain.

The F Gene of the Osaka-2 Strain of Measles Virus Derived from a Case of Subacute Sclerosing Panencephalitis Is a Major Determinant of Neurovirulence

“…In many SSPE strains, an A-to-Gbiased hypermutation occurred in the genome and destroyed the M protein-coding frames. In some cases, translation of the M protein is complicated by a transcriptional defect that leads to an almost exclusive synthesis of dicistronic P-M mRNA (4,12,13,61). Elucidation of the mechanism of the aberrant read-through transcription at the P-M gene junction revealed that a single deletion or mutation at the P gene end was responsible (5).…”

“…Plasmids encoding chimeric F proteins, OSA2-ext and OSA2-cyt, were previously described as Osa2/Toy and Mas/Osa2, respectively (6). The nucleotide sequences of the M, F, and H genes of the Osaka-2 strain were reported previously (4,23,47). Plasmids encoding mutant F proteins were constructed by a PCR-based method with synthetic primer pairs, and the inserts were confirmed by sequencing.…”

Mutations Affecting Transcriptional Termination in the P Gene End of Subacute Sclerosing Panencephalitis Viruses

“…A similar transcriptional alteration at the P-M gene junction of the MF strain of SSPE virus also has been reported (12). The P-M dicistronic RNA product has also been detected in cells infected with the Osaka-1 strain or with one of the sibling viruses of the Osaka-2 strain (1,34). In addition, the transcriptional patterns for the P and M genes differed from lot to lot of the Yamagata-1 strain (our unpublished observation).…”

Full‐Length Sequence Analysis of Subacute Sclerosing Panencephalitis (SSPE) Virus, a Mutant of Measles Virus, Isolated from Brain Tissues of a Patient Shortly after Onset of SSPE

“…The mutation rates of each viral protein-coding region range from 0.8% (L coding region) to 1.6% (H coding region), with the overall mutation rate being 1.2% (194/15,894) ( Table 2). It has been reported that the M gene of SSPE virus possesses a considerably large number of mutations (usually more than 30), the majority of which are the U-to-C biased hypermutation (2,9,20,45). We found that the mutation rate of the M coding region of SSPE-Kobe-1 was only 1.2% (12/1,008).…”