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首页> 外文期刊>Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases >Rodent host cell/Lassa virus interactions: evolution and expression of alpha -Dystroglycan, LARGE-1 and LARGE-2 genes, with special emphasis on the Mastomys genus.
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Rodent host cell/Lassa virus interactions: evolution and expression of alpha -Dystroglycan, LARGE-1 and LARGE-2 genes, with special emphasis on the Mastomys genus.

机译：啮齿动物宿主细胞/拉沙病毒相互作用：α-Dystroglycan，LARGE-1和LARGE-2基因的进化和表达，特别着重于 Mastomys 属。

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摘要

Arenaviruses are usually rodent-borne viruses that constitute a major threat for human health. Among them, Lassa Fever Virus (LFV) occurs in Western Africa where it infects hundreds of thousands of people annually. According to the most recent surveys, LFV is hosted by one of the multimammate rats, Mastomys natalensis, but has never been detected in its sibling and sometimes sympatric species Mastomys erythroleucus. This pattern suggests that intrinsic, i.e. genetic properties underlie such a drastic epidemiological difference (M. natalensis as a reservoir vs. M. erythroleucus as a non-reservoir species). Here we investigate genomic differences between these two closely related rodent species by focusing on three genes that have recently been described as pivotal for LFV/human cell interactions: Dystroglycan (the LFV cellular receptor), LARGE-1 and LARGE-2 (two enzymes that are essential to Dystroglycan functioning). For all three genes, sequence analyses showed that amino-acid chains undergo extremely strong purifying selective pressures, and indicated that no nucleotide (therefore no tertiary structure) change can be advocated to explain species-specific differences in LFV-cellular mediation. Nevertheless, preliminary studies of kidney-specific expression profiles suggested that important species-specific differences exist between Mastomys species. Taking into account current knowledge about LFV-human cell interactions, our results may point towards a possible role for LARGE-1 and LARGE-2 enzymes at the intracellular replication level of the virus, rather than at the LFV-host cell receptor binding step.Digital Object Identifier http://dx.doi.org/10.1016/j.meegid.2010.07.018
机译：沙粒病毒通常是啮齿动物传播的病毒，对人类健康构成重大威胁。其中，拉萨热病毒（LFV）发生在西非，每年感染成千上万的人。根据最近的调查，LFV由一只大型哺乳动物 Mastomys natalensis 寄主，但从未在其同胞物种或有时同胞物种 Mastomys erythroleucus 中被发现。这种模式表明，内在的，即遗传的特性是这种巨大的流行病学差异的基础（ natalnatal 作为水库与 erythroleucus 作为非水库物种）。在这里，我们通过关注最近被描述为对LFV /人细胞相互作用至关重要的三个基因来研究这两个密切相关的啮齿动物物种之间的基因组差异：Dystroglycan（LFV细胞受体），LARGE-1和LARGE-2（两种酶对糖原聚糖的功能至关重要）。对于所有三个基因，序列分析表明氨基酸链经历了极强的纯化选择性压力，并表明不能主张核苷酸（因此没有三级结构）的变化来解释LFV细胞介导的物种特异性差异。尽管如此，对肾脏特异性表达谱的初步研究表明， Mastomys 物种之间存在重要的物种特异性差异。考虑到有关LFV与人细胞相互作用的最新知识，我们的结果可能指向LARGE-1和LARGE-2酶在病毒的细胞内复制水平而不是在LFV-宿主细胞受体结合步骤中的可能作用。数字对象标识符http://dx.doi.org/10.1016/j.meegid.2010.07.018

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