Genetic diversity among lassa virus strains

Genetic diversity among lassa virus strains
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DOI:
10.1128/jvi.74.15.6992-7004.2000
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发表时间:
2000-08-01
影响因子:
5.4
通讯作者:
Nichol, ST
Nichol, ST
中科院分区:
医学2区
文献类型:
--
作者:
Bowen, MD;Rollin, PE;Nichol, ST

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阿拉伯病毒拉萨病毒引起拉沙热,这是一种病毒性出血热,在尼日利亚、塞拉利昂、利比里亚和几内亚等国流行,可能还会在西非其他地方流行。为了确定拉萨病毒毒株之间的遗传多样性程度,仅从54株拉萨病毒分离株中获得了部分核蛋白(NP)基因序列并进行了分析。系统发育分析表明,拉萨病毒由四个谱系组成,其中三个在尼日利亚,第四个在几内亚、利比里亚和塞拉利昂。在核苷酸水平和氨基酸水平上,株系的部分NP基因序列的变异高达27%和15%。Lassa菌株之间的遗传距离被发现与地理距离相关,而不是时间,并且没有发现“分子钟”的证据。建立了一种扩增和克隆阿拉伯拉萨病毒S病毒全长RNA的方法,并利用该方法获得了人疱疹病毒尼日利亚代表株拉萨病毒的NP和糖蛋白基因(gp1和gp2)的全序列。对代表四个谱系的四个拉萨病毒株的全长基因序列进行比较,结果表明,NP基因(核苷酸差异高达23.8%,氨基酸差异12.0%)比糖蛋白基因变异更大。尽管拉萨病毒株内的进化顺序尚未完全解决,但对全长NP、GP1和GP2基因序列的系统发育分析表明,尼日利亚拉萨病毒株是来自几内亚、利比里亚和塞拉利昂的毒株的祖先,与新大陆阿雷纳病毒相比,拉萨和其他东半球阿雷纳病毒要么经历了较短的分化期,要么进化速度较慢。这项研究是拉萨病毒基因变异的首次大规模检测。
The arenavirus Lassa virus causes Lassa fever, a viral hemorrhagic fever that is endemic in the countries of Nigeria, Sierra Leone, Liberia, and Guinea and perhaps elsewhere in West Africa. To determine the degree of genetic diversity among Lassa virus strains, partial nucleoprotein (NP) gene sequences mere obtained from 54 strains and analyzed. Phylogenetic analyses showed that Lassa viruses comprise four lineages, three of which are found in Nigeria and the fourth in Guinea, Liberia, and Sierra Leone. Overall strain variation in the partial NP gene sequence was found to be as high as 27% at the nucleotide level and 15% at the amino acid level. Genetic distance among Lassa strains was found to correlate with geographic distance rather than time, and no evidence of a "molecular clock" was found. A method for amplifying and cloning full-length arenavirus S RNAs was developed and used to obtain the complete NP and glycoprotein gene (GP1 and GP2) sequences for hvo representative Nigerian strains of Lassa virus. Comparison of full-length gene sequences for four Lassa virus strains representing the four lineages showed that the NP gene (up to 23.8% nucleotide difference and 12.0% amino acid difference) is more variable than the glycoprotein genes. Although the evolutionary order of descent within Lassa virus strains was not completely resolved, the phylogenetic analyses of full-length NP, GP1, and GP2 gene sequences suggested that Nigerian strains of Lassa virus were ancestral to strains from Guinea, Liberia, and Sierra Leone, Compared to the New World arenaviruses, Lassa and the other Old World arenaviruses have either undergone a shorter period of diverisification or are evolving at a slower rate. This study represents the first large-scale examination of Lassa virus genetic variation.