Evolutionary genetics of genotype H1 measles viruses in China from 1993 to 2012

Abstract

Virologic surveillance is a critical component of measles management. One of the criteria for verification of elimination of endemic measles is genetic analysis of wild-type viruses to demonstrate lack of an indigenous genotype. Measles is yet to be eliminated in China, and genotype H1 has been detected continuously since virologic surveillance was initiated in 1993. Virologic surveillance has been very active in China, providing a unique opportunity to conduct a detailed study of the evolution of a single, endemic genotype over a timespan of nearly two decades. Phylogenetic analysis performed on the 450 nt coding sequence for the C-terminal 150 amino acids of the nucleoprotein (N-450), fusion (F) gene and haemagglutinin (H) gene confirmed the continued circulation of genotype H1 viruses for 19 years. No evidence of selective pressure for the H protein was found. The substitution rates ranged from 0.75×10(-3) substitutions site(-1) year(-1) for H to 1.65×10(-3) substitutions site(-1) year(-1) for N-450. The time of most recent common ancestor (TMRCA) for genotype H1 was estimated as approximately 1985 (95 % highest probability density, 1979-1989). Finally, the overall diversity of measles sequences from China decreased from 2005 to 2012, coincident with a substantial decrease in measles cases. The results suggest that detailed evolutionary analyses should facilitate the documentation of eventual measles elimination in China. Moreover, the molecular approaches used in this study can be applied in other countries approaching measles elimination.

Fig. 1.

Phylogeny of N, F and H genes of genotype H1. Neighbour-joining phylogenetic trees were reconstructed using mega5. Sequences generated in this study are indicated with black circles. The names of viruses collected since 2010 are underlined. Groups corresponding to clusters 1 and 2 and bootstrap values greater than 70 % are indicated. Phylogenetic trees for N and F genes were rooted to genotype A Chinese vaccine strains Changchun47 and Shanghai191. GenBank ID numbers for the sequences used in the N, F and H datasets are presented in Table S1.

Fig. 2.

Maximum Clade Credibility (MCC) tree of H gene sequences of genotype H1 viruses from China. TMRCAs of interest are shown (see Table 1). Cluster 1 and cluster 2 are indicated. The complete MCC tree, featuring 95% HPDs node bars and posterior probabilities for the entire dataset is shown in Figure S3.

Fig. 3.

Bayesian skyline plots showing changes in the genetic diversity of H genes from genotypes H1 and B3 over time. Panel (a) shows sequence diversity for the H gene of genotype H1 viruses from China isolated between 1993 and 2012. The inset table shows the total number of measles cases reported in China over selected years. Panel (b) shows the diversity of H gene sequences for genotype B3 viruses detected in Africa. For both graphs, highlighted areas correspond to 95 % HPD intervals.