title: Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis.
abstract: Subacute Sclerosing Panencephalitis (SSPE), a rare lethal disease of children and young adults due to persistence of measles virus (MeV) in the brain, is caused by wild type (wt) MeV. Why MeV vaccine strains never cause SSPE is completely unknown. Hypothesizing that this phenotypic difference could potentially be represented by a molecular marker, we compared glycoprotein and matrix (M) genes from SSPE cases with those from the Moraten vaccine strain, searching for differential structural motifs. We observed that all known SSPE viruses have residues P64, E89, and A209 (PEA) in their M proteins whereas the equivalent residues for vaccine strains are either S64, K89, and T209 (SKT) as in Moraten or PKT. Through the construction of MeV recombinants, we have obtained evidence that the wt MeV-M protein PEA motif, in particular A209, is linked to increased viral spread. Importantly, for the 10 wt genotypes (of 23) that have had their M proteins sequenced, 9 have the PEA motif, the exception being B3, which has PET. Interestingly, cases of SSPE caused by genotype B3 have yet to be reported. In conclusion, our results strongly suggest that the PEA motif is a molecular marker for wt MeV at risk to cause SSPE.
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69007 Lyon, France ; Inserm, U1111, 69007 Lyon, France ; Ecole Normale Supérieure de Lyon, 69007 Lyon, France ; Centre International de Recherche en Infectiologie, Université Lyon 1, 69007 Lyon, France ; CNRS, UMR 5308, Lyon, France.
authors.forename: Hasan
authors.initials: H
authors.lastname: Kweder
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69007 Lyon, France ; Inserm, U1111, 69007 Lyon, France ; Ecole Normale Supérieure de Lyon, 69007 Lyon, France ; Centre International de Recherche en Infectiologie, Université Lyon 1, 69007 Lyon, France ; CNRS, UMR 5308, Lyon, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ainouze
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69007 Lyon, France ; Inserm, U1111, 69007 Lyon, France ; Ecole Normale Supérieure de Lyon, 69007 Lyon, France ; Centre International de Recherche en Infectiologie, Université Lyon 1, 69007 Lyon, France ; CNRS, UMR 5308, Lyon, France.
authors.forename: Joanna
authors.initials: J
authors.lastname: Brunel
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69007 Lyon, France ; Inserm, U1111, 69007 Lyon, France ; Ecole Normale Supérieure de Lyon, 69007 Lyon, France ; Centre International de Recherche en Infectiologie, Université Lyon 1, 69007 Lyon, France ; CNRS, UMR 5308, Lyon, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Gerlier
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69007 Lyon, France ; Inserm, U1111, 69007 Lyon, France ; Ecole Normale Supérieure de Lyon, 69007 Lyon, France ; Centre International de Recherche en Infectiologie, Université Lyon 1, 69007 Lyon, France ; CNRS, UMR 5308, Lyon, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Manet
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, 69007 Lyon, France ; Inserm, U1111, 69007 Lyon, France ; Ecole Normale Supérieure de Lyon, 69007 Lyon, France ; Centre International de Recherche en Infectiologie, Université Lyon 1, 69007 Lyon, France ; CNRS, UMR 5308, Lyon, France.
authors.forename: Robin
authors.initials: R
authors.lastname: Buckland