Feng Yan, Zhong Shu-ling, Xu Chang-ping, Lu Yi-yu
Virus Institute of Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou 310051, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2013 Jul;47(7):616-21.
To investigate the variations on hemagglutinin (H) gene of measles virus (MV) in Zhejiang province, and to analyze the differences with strains circulated both at home and abroad.
In total, 33 MV strains isolated in Zhejiang province between 1999 and 2011 were collected.RNA of the isolated MV strains was extracted and the complete sequences on H gene were amplified using RT-PCR assay. The products were compared with the Chinese vaccine strain Shanghai-191, which was downloaded from GenBank, and other 95 different MV strains from all over the world.
33 MV strains, isolated from the throat swab specimens collected from MV patients in Zhejiang province during 1999 to 2001, were used to conduct phylogenetic analysis with MV strains circulated in other areas of China during 1993 to 2007. The phylogenetic tree based on H gene sequences showed that all the Zhejiang MV strains located in H1a cluster, and no apparent time series and geographic restrictions were observed. Compared to the referenced vaccine strain Shanghai-191, the average variation rate on nucleotides and amino acids, and the evolutionary rate of H1a viruses from China during 2003 to 2011 were separately 5.15%, 4.44% and 5.81%, which were higher than the rates of H1a viruses during 1965 to 1993 (4.75%, 3.86% and 5.30%), and the rates of viruses during 1994 to 2002 (4.80%, 4.08% and 5.37%).However, the dn/ds ratios of strains within the three time periods were 0.19,0.21 and 0.23 respectively, which indicated that no evidence of positive selection was found on H1a MV strains during 1993 to 2011. A 24 stable amino acid variation sites on H gene was found between H1a viruses during 2003 to 2011 and the vaccine strain Shanghai-191. The largest variation occurred between vaccine and H1a strains, with 0.053 of the p-distance and 26-28 of amino acid mutations.However, only 15 stable amino acid variations were found between vaccine strain and genotype B3 or D4 strains.In addition, significant differences were found between H1a viruses and genotype B or D viruses, with 0.074 and 0.071 of p-distance and 27-33 of amino acid differences.
Significant differences were found on H gene between MV strains subtype H1a and vaccine strains and other genotype strains. The variations were enlarged with the time coursing; therefore, the surveillance on variation of Chinese MV strains should be taken into account.
研究浙江省麻疹病毒(MV)血凝素(H)基因的变异情况,并分析其与国内外流行毒株的差异。
收集1999年至2011年浙江省分离的33株MV毒株。提取分离的MV毒株RNA,采用RT-PCR法扩增H基因的完整序列。将产物与从GenBank下载的中国疫苗株上海-191以及来自世界各地的其他95株不同MV毒株进行比较。
选取1999年至2001年浙江省MV患者咽拭子标本中分离的33株MV毒株,与1993年至2007年中国其他地区流行的MV毒株进行系统发育分析。基于H基因序列构建的系统发育树显示,所有浙江MV毒株均位于H1a簇,未观察到明显的时间序列和地理限制。与参考疫苗株上海-191相比,2003年至2011年中国H1a病毒的核苷酸和氨基酸平均变异率以及进化率分别为5.15%、4.44%和5.81%,高于1965年至1993年H1a病毒的变异率(4.75%、3.86%和5.30%)以及1994年至2002年病毒的变异率(4.80%、4.08%和5.37%)。然而,三个时间段内毒株的dn/ds比值分别为0.19、0.21和0.23,这表明1993年至2011年期间H1a MV毒株未发现正选择证据。发现2003年至2011年的H1a病毒与疫苗株上海-191之间H基因上有24个稳定的氨基酸变异位点。疫苗株与H1a毒株之间的变异最大,p距离为0.053,氨基酸突变数为26 - 28个。然而,疫苗株与B3或D4基因型毒株之间仅发现15个稳定的氨基酸变异。此外,H1a病毒与B或D基因型病毒之间存在显著差异,p距离分别为0.074和0.071,氨基酸差异数为27 - 33个。
MV毒株H1a亚型与疫苗株及其他基因型毒株在H基因上存在显著差异。随着时间推移,变异有所扩大,因此应考虑对中国MV毒株的变异进行监测。