title: The phosphoprotein genes of measles viruses from subacute sclerosing panencephalitis cases encode functional as well as non-functional proteins and display reduced editing.
abstract: 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.
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Belfast, BT9 7BL Northern Ireland, UK.
authors.forename: E L
authors.initials: EL
authors.lastname: Millar
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Belfast, BT9 7BL Northern Ireland, UK; Department of Microbiology, Boston University School of Medicine and National Emerging Infectious Diseases Laboratories, Boston University, 620 Albany Street, Boston, MA 02118, United States.
authors.forename: L J
authors.initials: LJ
authors.lastname: Rennick
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Versbacher Straβe 7, D-97078 Würzburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Weissbrich
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Versbacher Straβe 7, D-97078 Würzburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schneider-Schaulies
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Belfast, BT9 7BL Northern Ireland, UK; Department of Microbiology, Boston University School of Medicine and National Emerging Infectious Diseases Laboratories, Boston University, 620 Albany Street, Boston, MA 02118, United States.
authors.forename: W P
authors.initials: WP
authors.lastname: Duprex
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Belfast, BT9 7BL Northern Ireland, UK. Electronic address: b.rima@qub.ac.uk.
authors.forename: B K
authors.initials: BK
authors.lastname: Rima
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008459:Measles virus / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D017393:RNA Editing; D013344:Subacute Sclerosing Panencephalitis / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D010750:Phosphoproteins; D014764:Viral Proteins
keywords: Absence of biased hypermutation; Editing; Genetic variation; Measles virus; Phosphoprotein gene; Subacute sclerosing panencephalitis