title: Mutations in the H, F, or M Proteins Can Facilitate Resistance of Measles Virus to Neutralizing Human Anti-MV Sera.
abstract: Although there is currently no evidence of emerging strains of measles virus (MV) that can resist neutralization by the anti-MV antibodies present in vaccinees, certain mutations in circulating wt MV strains appear to reduce the efficacy of these antibodies. Moreover, it has been hypothesized that resistance to neutralization by such antibodies could allow MV to persist. In this study, we use a novel in vitro system to determine the molecular basis of MV's resistance to neutralization. We find that both wild-type and laboratory strain MV variants that escape neutralization by anti-MV polyclonal sera possess multiple mutations in their H, F, and M proteins. Cytometric analysis of cells expressing viral escape mutants possessing minimal mutations and their plasmid-expressed H, F, and M proteins indicates that immune resistance is due to particular mutations that can occur in any of these three proteins that affect at distance, rather than directly, the native conformation of the MV-H globular head and hence its epitopes. A high percentage of the escape mutants contain mutations found in cases of Subacute Sclerosing Panencephalitis (SSPE) and our results could potentially shed light on the pathogenesis of this rare fatal disease.
authors.affiliation: INSERM-U1111, 69007 Lyon, France ; ENS-Lyon, 69007 Lyon, France ; University of Lyon, UCB-Lyon1, 69007 Lyon, France ; LabEx Ecofect, University of Lyon, 69007 Lyon, France.
authors.forename: Hasan
authors.initials: H
authors.lastname: Kweder
authors.affiliation: INSERM-U1111, 69007 Lyon, France ; ENS-Lyon, 69007 Lyon, France ; University of Lyon, UCB-Lyon1, 69007 Lyon, France ; LabEx Ecofect, University of Lyon, 69007 Lyon, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ainouze
authors.affiliation: School of Medicine, Dentistry and Biomedical Sciences, Queen's University, BT7 1NN Belfast, UK.
authors.forename: Sara Louise
authors.initials: SL
authors.lastname: Cosby
authors.affiliation: Institute of Immunology, Public Research Center for Health/LNS, 20A rue Auguste Lumière, L-1950 Luxemburg, Grand-Duchy of Luxembourg, Luxembourg.
authors.forename: Claude P
authors.initials: CP
authors.lastname: Muller
authors.affiliation: INSERM-U1111, 69007 Lyon, France ; ENS-Lyon, 69007 Lyon, France ; University of Lyon, UCB-Lyon1, 69007 Lyon, France ; LabEx Ecofect, University of Lyon, 69007 Lyon, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Lévy
authors.affiliation: INSERM-U1111, 69007 Lyon, France ; ENS-Lyon, 69007 Lyon, France ; University of Lyon, UCB-Lyon1, 69007 Lyon, France ; LabEx Ecofect, University of Lyon, 69007 Lyon, France.
authors.forename: Els
authors.initials: E
authors.lastname: Verhoeyen
authors.affiliation: INSERM-U1111, 69007 Lyon, France ; ENS-Lyon, 69007 Lyon, France ; University of Lyon, UCB-Lyon1, 69007 Lyon, France ; LabEx Ecofect, University of Lyon, 69007 Lyon, France.
authors.forename: François-Loïc
authors.initials: FL
authors.lastname: Cosset
authors.affiliation: INSERM-U1111, 69007 Lyon, France ; ENS-Lyon, 69007 Lyon, France ; University of Lyon, UCB-Lyon1, 69007 Lyon, France ; LabEx Ecofect, University of Lyon, 69007 Lyon, France.
authors.forename: Evelyne
authors.identifier: 0000-0001-7619-9982
authors.initials: E
authors.lastname: Manet
authors.affiliation: INSERM-U1111, 69007 Lyon, France ; ENS-Lyon, 69007 Lyon, France ; University of Lyon, UCB-Lyon1, 69007 Lyon, France ; LabEx Ecofect, University of Lyon, 69007 Lyon, France.
authors.forename: Robin
authors.initials: R
authors.lastname: Buckland