Rapid degradation restricts measles virus matrix protein expression in a subacute sclerosing panencephalitis cell line

Abstract

Measles virus matrix protein expression is restricted in the persistently infected brain cells of patients with the chronic neurological disease subacute sclerosing panencephalitis (SSPE). Prior studies of the nature of this restriction have identified polyadenylylated matrix gene-encoded RNA transcripts unable to direct effective translation. The defective nature of these mRNAs readily accounted for the inability to detect matrix protein in these persistently infected cells and suggested that in SSPE the restriction of matrix protein expression is achieved by preventing its synthesis. Recently, however, we reported evidence that matrix protein is synthesized in at least one example of this persistent infection, the SSPE cell line IP-3-Ca. In this case, failure of matrix protein to accumulate normally accounted for its restricted expression [Sheppard, R. D., Raine, C. S., Bornstein, M. B. & Udem, S. A. (1985) Science 228, 1219-1221]. To clarify the nature of the restriction displayed by IP-3-Ca cells, the synthesis and fate of the matrix protein of this SSPE cell line were examined in detail. No evidence of constraints on the efficiency of matrix protein mRNA transcription or translation was found. Instead, the restricted expression proved to be the result of rapid posttranslational degradation of matrix protein. We suggest that matrix protein gene mutations incurred in the course of genome replication are likely to be responsible for the diversity of observed mechanisms restricting matrix protein expression. In that event, the nature and position of the nucleotide substitution(s) would be the determinants of the level at which restricted expression is achieved.