Genetic Characterization of the Hemagglutinin Genes of Wild-Type Measles Virus Circulating in China, 1993–2009

Abstract

BackgroundChina experienced several large measles outbreaks in the past two decades, and a series of enhanced control measures were implemented to achieve the goal of measles elimination. Molecular epidemiologic surveillance of wild-type measles viruses (MeV) provides valuable information about the viral transmission patterns. Since 1993, virologic surveillnace has confirmed that a single endemic genotype H1 viruses have been predominantly circulating in China. A component of molecular surveillance is to monitor the genetic characteristics of the hemagglutinin (H) gene of MeV, the major target for virus neutralizing antibodies.Principal FindingsAnalysis of the sequences of the complete H gene from 56 representative wild-type MeV strains circulating in China during 1993–2009 showed that the H gene sequences were clustered into 2 groups, cluster 1 and cluster 2. Cluster1 strains were the most frequently detected cluster and had a widespread distribution in China after 2000. The predicted amino acid sequences of the H protein were relatively conserved at most of the functionally significant amino acid positions. However, most of the genotype H1 cluster1 viruses had an amino acid substitution (Ser240Asn), which removed a predicted N-linked glycosylation site. In addition, the substitution of Pro397Leu in the hemagglutinin noose epitope (HNE) was identified in 23 of 56 strains. The evolutionary rate of the H gene of the genotype H1 viruses was estimated to be approximately 0.76×10−3 substitutions per site per year, and the ratio of dN to dS (dN/dS) was <1 indicating the absence of selective pressure.ConclusionsAlthough H genes of the genotype H1 strains were conserved and not subjected to selective pressure, several amino acid substitutions were observed in functionally important positions. Therefore the antigenic and genetic properties of H genes of wild-type MeVs should be monitored as part of routine molecular surveillance for measles in China.

Analysis of complete genomes of the rubella virus genotypes 1E and 2B which circulated in China, 2000–2013

“…However, different regions of the genome appeared to evolve at different rates. These rates are faster than the average for alphaviruses (1–8 × 10 −4 substitutions/site/year)32 and measles virus (0.65 × 10 −3 substitutions/site/year based on the the H gene)33 but slower than polio virus (synonymous substitutions rate ~1 × 10 −2 substitutions/site/year)34. RV is known to have a high GC content and slow replication in tissue culture.…”

Molecular evolution of haemagglutinin (H) gene in measles virus

“…Previous reports have discussed the evolution rates of the H gene in MeV as ranging from 7.28 × 10 −6 to 6 × 10 −3 substitutions/site/year 22 25 26 27 . In the present study, we estimated that the mean rate of the molecular evolution of MeV H gene as 9.02 × 10 −4 substitutions/site/year.…”

Mutational Analysis of Measles Virus Suggests Constraints on Antigenic Variation of the Glycoproteins

“…However, this antigenic “drift” does not appreciably occur in the MeV F and H glycoproteins. The molecular basis for the lack of emergent antigenically distinct strains of MeV, relative to other related negative sense RNA virus like influenza A virus, is currently unclear (Fayolle et al, 1999; Lech et al, 2013; Xu et al, 2013). Given that MeV does not undergo major antigenic changes, it is possible that the glycoproteins of MeV are under a rigid, but as of yet undefined, constraint that prevents this evolution from occurring.…”