The phosphoprotein genes of measles viruses from subacute sclerosing panencephalitis cases encode functional as well as non-functional proteins and display reduced editing

•the variability of measles virus (MV) RNA sequencers in the brains of 7 subacute sclerosingpanencephalitis (SSPE) patients is larger than what is observed in acute infection.•the co-trancriptional editing which gives rise to mRNAs that encode the V protein, which is important in counteracting innate immune responses during acute measles is much reduced in thirteen clone sets derived from the P/V/C genes of MV RNA extracted from brains of a unique collection of seven cases of (SSPE).•the P genes in MV from SSPE cases were not altered by biased hypermutation.•most but not all SSPE derived phospho- (P) proteins were functional in minigenome replication/transcription assays.

Products expressed from the second (P/V/C) gene are important in replication and abrogating innate immune responses during acute measles virus (MV) infection. Thirteen clone sets were derived from the P/V/C genes of measles virus (MV) RNA extracted from brains of a unique collection of seven cases of subacute sclerosing panencephalitis (SSPE) caused by persistent MV in the central nervous system (CNS). Whether these functions are fully maintained when MV replicates in the CNS has not been previously determined. Co-transcriptional editing of the P mRNAs by non-template insertion of guanine (G) nucleotides, which generates mRNAs encoding the viral V protein, occurs much less frequently (9%) in the SSPE derived samples than during the acute infection (30–50%). Thus it is likely that less V protein, which is involved in combatting the innate immune response, is produced. The P genes in MV from SSPE cases were not altered by biased hypermutation but exhibited a high degree of variation within each case. Most but not all SSPE derived phospho-(P) proteins were functional in mini genome replication/transcription assays. An eight amino acid truncation of the carboxyl-terminus made the P protein non-functional while the insertion of an additional glycine residue by insertion of G nucleotides at the editing site had no effect on protein function.