GENETIC CHARACTERIZATION OF THE HEMAGGLUTININ GENES OF WILD-TYPE MEASLES VIRUS CIRCULATING IN CHINA, 1993–2009

Wednesday, 23rd of April 2014

[source]PLoS One[|source]

The genome of measles virus contains six genes that encode the nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin (H), and polymerase (L) proteins. The H protein, an 80 kilodalton (kD) glycoprotein, is responsible for receptor-binding and is the major target for neutralizing antibodies. The H protein usually contains five potential N-linked glycosylation sites which are clustered at amino acid positions 168, 187, 200, 215, 238. Some genotypes have an additional N-linked glycosylation site at position 416.

In this report, the authors describe the genetic variability of the H genes of measles viruses circulating throughout China over a 17-year period. The report provides the first detailed report of the sequences of the H genes of Chinese measles viruses as well as a unique opportunity to analyze genetic changes in the H genes from a single genotype of measles virus over an extended period of time. More details are accessible at:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779233/

 

Abstract

BACKGROUND: China 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 surveillance 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 FINDINGS: Analysis 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.

CONCLUSIONS:  Although 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.