2017年珠海市暴发流行麻疹病毒遗传进化研究

Phylogenetic analysis on measles viruses in Zhuhai outbreak during 2017

目的分析2017年广东省珠海市麻疹暴发流行期间麻疹病毒基因组序列和可能的传播来源。方法分段扩增2017年珠海市的第1株和最后1株麻疹病毒毒株全基因组并测序，通过末端重叠序列拼接组成病毒全基因组序列并上传至GenBank。参考已公布的麻疹病毒全基因组序列，对病毒进行进化分析。结合流行病学调查，推测病毒的可能来源及传播途径。通过核苷酸序列推导病毒氨基酸序列，比对疫苗株Shanghai191，分析病毒氨基酸变异的意义。结果拼接后的麻疹病毒MVs／Zhuhai．CHN／10．17／2[H11（GenBank序列号：MG972194）基因组全长15894个核苷酸，编码6个结构蛋白和2个非结构蛋白。序列进化分析表明，病毒属麻疹病毒H1型。遗传距离上，与2007年分离自浙江的KJ755987．1的核苷酸同源性最高，达99％（15783／15894）。病毒N、P、V、C、M、F、H、L蛋白氨基酸序列与疫苗株Shanghai191的一致性分别为96．6％（507／525）、98．2％（498／507）、97．7％（292／299）、96．8％（180／186）、99．1％（332／335）、96．6％（534／553）、98．5％（08／617）和99．3％（2168／2183）。结论2017年珠海市麻疹病毒可能由浙江省的感染者传播并导致珠海本地暴发流行。病毒N、P、L和V蛋白的氨基酸变异可能使其在复制和转录功能、致病力、诱导宿主T细胞免疫功能及细胞体液免疫平衡方面与疫苗株Shanghai191出现差异。

Objective To analyze the genome of the measles virus strains isolated in Zhuhai city Guangdong Province and to explore the possible viral origin. Methods The fragmentated genome was amplified and sequenced. The sequencing results were assembled into a complete viral genomic sequence by terminal overlapped method. The viral genomic sequence were submitted to the GenBank. The phylogenetic trees were constructed by compared the genomic sequence with sequences presently available on GenBank. The possible sources and the spreading routes of the virus were conjectured accompanied with epidemiological investigation. The amino acid sequence of the virus was inferred according to the sequence and the significance of the mutation was analyzed based on the vaccine strain - Shanghail91. Results The whole genomic sequence of MVs/Zhuhai.CHN/1 0.17/2[H1 ] （Accession No： MG972194） was 15 894bp in length and coded six structural proteins and two non-structural proteins. The phylogenetic analysis demonstrated that it was the nearest to KJ755987.1 （99% identity, 15 783/15 894）. The consistency of the amino acide sequences of N, P, V, C, M, F, H and L proteins of MG972194 with vaccine strain - Shanghail91 were 96.6% （507/525）, 98.2% （498/507）, 97.7% （292/299）, 96.8% （180/186）, 99.1% （332/335）, 96.6% （534/553）, 98.5% （608/617） and 99.3% （2 168/2 183）, respectively. Conclusions The epidemiological evidences supported that measles virus type H1 strains causing local outbreaks in Zhuhai during 2017 were likely to be originated from patients of Zhejiang province. The amino acide mutation within N, P, L and V proteins seemed to modify capabilities of MG972194 in genome duplication and transcription, pathopoiesia, inducing host T cell immunity and balance between the cellular and humoral immunity.