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.


RESULTS
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.
Regional Reference Measles Laboratory for the WHO Western Pacific Region, Key Laboratory of Medical Virology Ministry of Health, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing, China.
Songtao
S
Xu
Yan
Y
Zhang
Zhen
Z
Zhu
Chunyu
C
Liu
Naiying
N
Mao
Yixin
Y
Ji
Huiling
H
Wang
Xiaohong
X
Jiang
Chongshan
C
Li
Wei
W
Tang
Daxing
D
Feng
Changyin
C
Wang
Lei
L
Zheng
Yue
Y
Lei
Hua
H
Ling
Chunfang
C
Zhao
Yan
Y
Ma
Jilan
J
He
Yan
Y
Wang
Ping
P
Li
Ronghui
R
Guan
Shujie
S
Zhou
Jianhui
J
Zhou
Shuang
S
Wang
Hong
H
Zhang
Huanying
H
Zheng
Leng
L
Liu
Hemuti
H
Ma
Jing
J
Guan
Peishan
P
Lu
Yan
Y
Feng
Yanjun
Y
Zhang
Shunde
S
Zhou
Ying
Y
Xiong
Zhuoma
Z
Ba
Hui
H
Chen
Xiuhui
X
Yang
Fang
F
Bo
Yujie
Y
Ma
Yong
Y
Liang
Yake
Y
Lei
Suyi
S
Gu
Wei
W
Liu
Meng
M
Chen
David
D
Featherstone
Youngmee
Y
Jee
William J
WJ
Bellini
Paul A
PA
Rota
Wenbo
W
Xu
D002681:China; D019143:Evolution, Molecular; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006389:Hemagglutinins, Viral / Q000235:genetics*; D006801:Humans; D008457:Measles / Q000235:genetics* / Q000635:transmission / Q000821:virology; D008459:Measles virus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D008969:Molecular Sequence Data; D013997:Time Factors
D006389:Hemagglutinins, Viral