Antigenic Drift Defines a New D4 Subgenotype of Measles Virus

Phylogenetic relationships of the MeV-N gene (left) and MeV-H gene (right) of measles virus genotype D4. The evolutionary history was inferred by using the maximum likelihood method based on the general time-reversible model. Measles virus genotype A (MVi/Maryland.USA/0.54) was used for rooting the tree. Evolutionary analyses were conducted with MEGA 6.06. Statistical support for grouping is shown as bootstrap values (1,000 replicated). Values of >80% are indicated at the deep node. The bar represents the genetic distance. The subgenotype classification is illustrated. Sequences were retrieved from the National Center for Biotechnology Information (NCBI) GenBank database and are named according to World Health Organization guidelines (Table 1).

Sequence alignment of the MeV-H genes of genotype D4 viruses. The GenBank accession numbers for the MeV-H gene sequences used in the sequence alignment are shown in Table 1.

Leu249Pro amino acid change as the driver mutation for escape of MeV subgenotype D4.2. (A) Neutralization activity of the NE-targeting antibodies against MeV genotypes. The neutralization assay was performed and data are represented as indicated in the legend of Fig. 1. Of note, only genotype D6 and the so-called subgenotype D4.2 viruses escape neutralization by all 3 antibodies. (B) Sequence alignment (amino acids 235 to 255) of MeV-H proteins among the MeV genotypes used in this study. (C) Effect of amino acid mutations on NE-targeting antibody neutralization. (D) NE-targeting antibody binding to MeV-H proteins. MAb binding was determined by an enzyme-linked immunosorbent assay after the addition of a nonsaturating concentration of MAbs to microtiter plates coated with the FLAG-tagged MeV-H protein. The amount of anti-FLAG antibody binding was used as a loading control. Binding values were normalized to those obtained with MeV-H genotype A. Means and standard deviations for a representative experiment performed in duplicate are shown.