Characteristics and Genomic Diversity of Measles Virus From Measles Cases With Known Vaccination Status in Shanghai, China

Abstract

Although the highly effective measles vaccine has dramatically reduced the incidence of measles, measles, and outbreaks continue to occur in individuals who received the measles vaccine because of immunization failure. In this study, patients who have definite records of immunization were enrolled based on measles surveillance in Shanghai, China, from 2009 to 2017, and genomic characteristics regarding viruses retrieved from these cases provided insights into immunization failure. A total of 147 complete genomes of measles virus (MV) were obtained from the laboratory-confirmed cases through Illumina MiSeq. Epidemiological, and genetic characteristics of the MV were focused on information about age, gender, immunization record, variation, and evolution of the whole genome. Furthermore, systematic genomics using phylogeny and selection pressure approaches were analyzed. Our analysis based on the whole genome of 147 isolates revealed 4 clusters: 2 for the genotype H1 (clusters named H1-A, including 73 isolates; H1-B, including 72 isolates) and the other 2 for D8 and B3, respectively. Estimated nucleotide substitution rates of genotype H1 MV derived using genome and individual genes are lower than other genotypes. Our study contributes to global measles epidemiology and proves that whole-genome sequencing was a useful tool for more refined genomic characterization. The conclusion indicates that vaccination may have an effect on virus evolution. However, no major impact was found on the antigenicity in Shanghai isolates.

Keywords: Shanghai isolates; comparative genomics; complete genome sequences; genetic diversity; measles virus; vaccine failure.

FIGURE 1

Genotyping of MV strains circulating in Shanghai, China, between 2009 and 2017. (A) Based on the full-length 150 amino acid sequence of the N terminal 450 bp in the nucleoprotein region; (B) H gene. A maximum-likelihood phylogenetic reconstructed by MEGA 6 was performed with 147 Shanghai-MV strains and 24 genotype-references from the WHO’s list for genotyping. ◆: reference strains from genotype H1; ▲: reference strains from clusters H1-A.

FIGURE 2

Comparison of the vaccine group and non-vaccine group for characterizing the measles virus genome. (A) Pairwise distance based on 147 full-length measles virus sequences. (B) The estimated average divergence in individual genes is based on nucleotide (nt) sequences or predicted amino acid (aa) sequences.

FIGURE 3

Maximum clade credibility tree of 147 Shanghai and global MV isolates derived using the whole genome. The D8, B3, and H1-A, H1-B are highlighted using green, purples, yellows, and blues, respectively.