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中国GB病毒C/庚型肝炎病毒的遗传异质性与分子流行病学

Genetic heterogeneity and molecular epidemiology of GB virus C/hepatitis G virus in China.

作者信息

An P, Luo H, Lu T, O'Brien S J, Winkler C

机构信息

ntramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA.

出版信息

J Hum Virol. 2000 Nov-Dec;3(6):299-305.

PMID:11100910
Abstract

OBJECTIVE

The inter- and intrapatient genetic variation of GB virus C (GBV-C)/hepatitis G virus (HGV) was investigated to characterize the molecular epidemiologic profile of GBV-C/ HGV infection in China, an area endemic for viral hepatitis. The intrapatient variation of hepatitis C virus (HCV) from the same patients was compared to that of GBV-C/HGV.

STUDY DESIGN/METHODS: GB virus C/HGV RNA was amplified by polymerase chain reaction in 88 patients with hepatitis C, hepatitis B or presumed non-A-E hepatitis from three cities in China. Five clones of the GBV-C/HGV NS3 region were sequenced from each GBV-C/HGV RNA-positive patient. The corresponding region of HCV was also sequenced from patients co-infected with HCV. Representative sequences of the GBV-C/HGV NS3 region from each patient and those of isolates from other continents were subjected to phylogenetic analyses.

RESULTS

GB virus C/HGV was detected in 22 (25.25%) of 88 patients: 9 (21.4%) of 42 patients with presumed non-A-E hepatitis, 10 (27.7%) of 36 patients with hepatitis C, 3 (30.0%) in 10 patients with hepatitis B and C, and in none of 60 volunteer blood donors. The extent of nucleotide variation was less between Chinese isolates (2.4-17%; median, 10.4%) than between Chinese isolates and seven isolates from outside China (10.5-19.5%; median, 15.3%). Intrapatient sequence variation ranged from 0 to 1.75%, with a mean of 0.57 +/- 0.51%. Phylogenetic analysis grouped most Chinese isolates into four geographically specific clusters with a divergence of 10% to 16% from each other. The ratio of nonsynonymous to synonymous substitutions of GBV-C/HGV (Ka/Ks 0.019) was much lower than for HCV (0.071) in the same patients.

CONCLUSION

Chinese isolates of GBV-C/HGV are genetically distinct. There are local strains as well as shared strains between different locales. The extent of amino acid sequence conservation suggests strong selection against nonsynonymous substitutions in the GBV-C/HGV genome.

摘要

目的

研究中国(病毒性肝炎的地方性流行区)GB病毒C(GBV-C)/庚型肝炎病毒(HGV)的患者间及患者内基因变异,以描述GBV-C/HGV感染的分子流行病学特征。将同一患者的丙型肝炎病毒(HCV)的患者内变异与GBV-C/HGV的进行比较。

研究设计/方法:采用聚合酶链反应对来自中国三个城市的88例丙型肝炎、乙型肝炎或疑似非甲-戊型肝炎患者的GB病毒C/HGV RNA进行扩增。对每个GBV-C/HGV RNA阳性患者的GBV-C/HGV NS3区的五个克隆进行测序。同时对合并感染HCV的患者的HCV相应区域进行测序。对每个患者的GBV-C/HGV NS3区的代表性序列以及来自其他大洲的分离株的序列进行系统发育分析。

结果

88例患者中有22例(25.25%)检测到GB病毒C/HGV:42例疑似非甲-戊型肝炎患者中有9例(21.4%),36例丙型肝炎患者中有10例(27.7%),10例乙型和丙型肝炎患者中有3例(30.0%),60例无偿献血者中均未检测到。中国分离株之间的核苷酸变异程度(2.4% - 17%;中位数为10.4%)低于中国分离株与来自中国以外的七个分离株之间的变异程度(10.5% - 19.5%;中位数为15.3%)。患者内序列变异范围为0至1.75%,平均为0.57±0.51%。系统发育分析将大多数中国分离株分为四个地理特异性簇,彼此之间的差异为10%至16%。同一患者中GBV-C/HGV的非同义替换与同义替换的比率(Ka/Ks 0.019)远低于HCV(0.071)。

结论

中国的GBV-C/HGV分离株在基因上是不同的。不同地区之间既有本地菌株,也有共享菌株。氨基酸序列保守程度表明对GBV-C/HGV基因组中的非同义替换有强烈的选择作用。

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