【摘要】 目的为了解不同省(自治区、直辖市,下同)2003年流行的麻疹野病毒是否存在基因型或亚型的差异。方法对2003年15个省分离的107株麻疹病毒进行了分子流行病学研究,对同一年份不同省流行的麻疹野病毒的基因特征及分子差异做了进一步的分析。用逆转录-聚合酶链反应(reversetranscriptpolymerasechainreaction,RT-PCR)从107株麻疹病毒中扩增出核蛋白(nucleoprotein,N)基因羧基(COOH)末端450个核苷酸片段。通过对扩增产物进行核苷酸序列测定和分析,构建基因亲缘性关系树,进行遗传距离分析。结果106株为麻疹病毒H1基因型;1株属于A基因型,为沪191(S191)疫苗株。106株H1基因型毒株分成2个亚型,101株为H1a,5株为H1b基因亚型。2003年H1b亚型主要流行于海南、四川、上海、贵州省;而H1a在全国广泛分布;未发现H1c基因亚型,该亚型1993~1994年曾是北京、山东、河北、湖南省流行的优势毒株。对比2003年与1993~2002年流行的麻疹病毒基因亚型,H1a呈上升趋势,H1b亚型在所有H1基因型中的比例由1995~2002年的24·3%下降到2003年的4·7%,而H1c亚型逐渐消失。对2003年分离的病毒进行省内和不同省间遗传距离的比较证明,各省内的毒株变异范围在0%~6·1%(0~27个核苷酸差异);各省间的变异范围在0%~4·3%(0~20个核苷酸差异);省内差异最大值大于省间差异。结论中国最近11年来流行的麻疹病毒基因亚型趋势为:H1a呈上升趋势,逐渐成为优势亚型;H1b亚型逐年降低转为弱势;H1c亚型逐渐消失。2003年麻疹变异毒株呈散在分布,无明显地域性。同时表明,中国的麻疹流行是由H1a和H1b中的许多不同病毒株造成的多个传播链引起的。讨论了在中国继续开展麻疹病毒分子流行病学监测的必要性和紧迫性,并展望了分子流行病学监测对于中国控制和消除麻疹的应用前景。更多还原

【Abstract】 Objective To study the genetic characterization of 107 measles viruses isolated from throat swabs or urine specimens of measles patients in 15 provinces of the People’s Republic of China in 2003. Methods Viral RNA prepared from measles viruses isolates was used as a template for RT-PCR.The C-terminal region of the N-gene was amplified and sequenced. Phylogenetic analysis and the diversity analysis were done with MEGA version 2.1. Results The analysis of 450[CM)]nucleotides sequence of COOH terminal of nucleoprotein（N） genes of 107 isolates indicated that all the isolates belonged to H₁ genotype, except 1 isolate from Xinjiang Province,Xinjiang 03-1,was A genotype. Xinjiang 03-1 was most closely to China vaccine strain S191,which belonged to A genotype along with Edmonston strain. The phylogenetic analysis of the 107 China isolates compared with WHO reference strains also showed that H₁ genotype was still the predominant virus in China in 2003, comparing with the measles virus circulated in 1995～2002.106 H₁ genotype isolates were further divided into 2 subgenotype,H₁a and H₁b.101 isolates were belonged to H₁a which distributed countrywide without distinct geographical regions; 5 isolates were H₁b which mainly distributed in Hainan,Sichuan,Shanghai, and Guizhou provinces in South China. No H₁c isolate was found in 2003, but H₁c had been predominantly circulating in Shandong, Beijing, Hebei, and Hunan provinces in China between 1993 and 1994.The analysis of the dynamic epidemic trend of measles virus circulated in China from 1993 to 2003 indicated that H₁a was the mainly predominant subgenotype following with the H₁b subgenotype descending from 1995 to 2003,the rate of the H₁b subgenotype in all of the H₁ genotype isolates was 24.3% and 4.7% in 1995～2002 and 2003, respectively;the H₁c subgenotype nearly disappeared after the year of 2000.The average genetic p-distances of isolates within and between the provinces showed that the range is 0%-6.1% （0-27 nucleotide variation） and 0.1%-4.3% （0-20 nucleotide variation） respectively. Conclusion There were many different H₁a and H₁b viruses co-circulating in different provinces and measles outbreaks were caused by many different measles viruses by different transmission chains in China.The diversity of the isolates between and within provinces has not distinct geographical characteristics.Measles virus surveillance data in China have already contributed to the global measles virus surveillance and measles elimination program.It is much more important and necessary to continue to do molecular epidemiology surveillance in China for the accelerating measles control program and measles elimination in future in China.更多还原