Antigenic drift defines a new D4 subgenotype of measles virus

Miguel Ángel Muñoz-Alía, Claude P. Muller, Stephen J. Russell

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The measles virus hemagglutinin (MeV-H) protein is the main target of protective neutralizing antibodies. Using a panel of monoclonal antibodies (MAbs) that recognize known major antigenic sites in MeV-H, we identified a D4 genotype variant that escapes neutralization by MAbs targeting the neutralizing epitope (NE) antigenic site. By site-directed mutagenesis, L249P was identified as the critical mutation disrupting the NE in this genotype D4 variant. Forty-two available D4 genotype gene sequences were subsequently analyzed and divided into 2 groups according to the presence or absence of the L249P MeV-H mutation. Further analysis of the MeV-N gene sequences of these 2 groups confirmed that they represent clearly definable, sequence-divergent D4 subgenotypes, which we named subgenotypes D4.1 and D4.2. The subgenotype D4.1 MeVs were isolated predominantly in Kenya and Ethiopia, whereas the MAb-resistant subgenotype D4.2 MeVs were isolated predominantly in France and Great Britain, countries with higher vaccine coverage rates. Interestingly, D4.2 subgenotype viruses showed a trend toward diminished susceptibility to neutralization by human sera pooled from approximately 60 to 80 North American donors. Escape from MAb neutralization may be a powerful epidemiological surveillance tool to monitor the evolution of new MeV subgenotypes.

Original languageEnglish (US)
Article numbere00209-17
JournalJournal of virology
Volume91
Issue number11
DOIs
StatePublished - Jun 1 2017

Keywords

  • Antibody-mediated neutralization
  • Antigenic variation
  • Immune evasion
  • Measles virus genotypes
  • Measles virus hemagglutinin
  • Viral epitopes
  • Virus evolution

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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