Molecular epidemiology of measles viruses in China, 1995–2003

This report describes the genetic characterization of 297 wild-type measles viruses that were isolated in 24 provinces of China between 1995 and 2003. Phylogenetic analysis of the N gene sequences showed that all of the isolates belonged to genotype H1 except 3 isolates, which were genotype A. The nucleotide sequence and predicted amino acid homologies of the 294-genotype H1 strains were 94.7%–100% and 93.3%–100%, respectively. The genotype H1 isolates were divided into 2 clusters, which differed by approximately 2.9% at the nucleotide level. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Even though other measles genotypes have been detected in countries that border China, this report shows that genotype H1 is widely distributed throughout the country and that China has a single, endemic genotype. This important baseline data will help to monitor the progress of measles control in China

Rubella Virus Genotypes in the People's Republic of China between 1979 and 2007: a Shift in Endemic Viruses during the 2001 Rubella Epidemic▿ †

The incidence of rubella cases in China from 1991 to 2007 was reviewed, and the nucleotide sequences from 123 rubella viruses collected during 1999 to 2007 and 4 viral sequences previously reported from 1979 to 1984 were phylogenetically analyzed. Rubella vaccination was not included in national immunization programs in China before 2007. Changes in endemic viruses were compared with incidences of rubella epidemics. The results showed that rubella epidemics occur approximately every 6 to 8 years (1993/1994, 2001, and 2007), and a shift of disease burden to susceptible young adults was observed. The Chinese rubella virus sequences were categorized into 5 of the 13 rubella virus genotypes, 1a, 1E, 1F, 2A, and 2B; cocirculations of these different genotypes were found in China. In Anhui province, a shift in the predominant genotype from 1F and 2B to 1E coincided with the 2001 rubella epidemic. This shift may have occurred throughout China during 2001 to 2007. This study investigated the genotype distribution of rubella viruses in China over a 28-year period to establish an important genetic baseline in China during its prevaccination era

Genetic characterization of the hemagglutinin genes of wild-type measles virus circulating in china, 1993-2009.

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 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 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

Primers used for amplification and sequencing of the entire H gene.

a<p>: s, sense orientation; as, antisense orientation.</p>b<p>: the primers' nucleotide locations and range on the basis of the Measles prototype strain: Edmonston complete genome (GenBank ID: AF266288).</p>c<p>: Length of the PCR product or use of the primer for sequencing (Seq).</p

Alignment of the predicted amino acid sequences of the partial H gene.

<p>The variation of amino acid Ser240Asn (highlighted in blue) leads to the absence of a glycosylation site; the exchange of Pro397Leu (highlighted in pink) that results in loss of recognition of two monoclonal antibodies directed against HNE; the amino acid residues of putative binding sites for CD46, SLAM and seven cysteine residues were highlighted in red, yellow and purple, respectively.</p

Phylogenetic relationship based on the complete H gene sequences.

<p>Neighbour-joining tree was reconstructed with full-length H gene sequences from 56 genotype H1 wild-type measles isolates from mainland China, the WHO reference strains of each genotype and Chinese vaccine strains. The sequences of the circulating strains in 1993–1994 and in 2000–2009 are indicated by symbol “▴” and “•”, respectively, each color of symbol “•” represents the annually circulating strains. The genotype H2 reference strain below cluster 2 which is also marked by a triangle was identified in 1994, China. The branches for the different lineages are marked by various colors. The WHO standard name of MeVs and GenBank accession numbers of all the sequences are available in the figure. Numbers at nodes represent the percentage of 1,000 bootstrap replicates (values <70 are not shown). Bar, 0.005 nucleotide substitutions per site.</p

Reported measles cases and incidence in China, 1991–2009.

<p>The number above the column represents the number of representative measles strains selected for the complete H gene sequence analysis. Blue bars indicate the number of reported measles cases and yellow solid diamonds indicate the incidence (/100,000 population) of each year, the Arabic numerals above the x-axis indicates the number of deaths. X-axis denotes year, y-axis on left denotes reported number of cases and y-axis on right denotes the incidence per 100,000 population.</p