Genetic mapping of specific interactions between Aedes aegypti mosquitoes and dengue viruses.
Genetic mapping of specific interactions between Aedes aegypti mosquitoes and dengue viruses.
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DOI：
10.1371/journal.pgen.1003621
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Lambrechts L
中科院分区：
文献类型：
--
作者：
Fansiri T;Fontaine A;Diancourt L;Caro V;Thaisomboonsuk B;Richardson JH;Jarman RG;Ponlawat A;Lambrechts L
在无脊椎动物系统中，经常观察到宿主基因型和病原基因型之间的特异性相互作用（G×G相互作用）。这种特异性挑战了我们目前对无脊椎动物防御病原体的理解，因为它与已知的无脊椎动物免疫反应的有限区分能力形成对比。然而，由于缺乏一种机械的解释，人们对G×G相互作用背后的宿主因素的性质提出了质疑。在这项研究中，我们的目的是确定在自然界中观察到的登革病毒及其埃及伊蚊载体之间的G×G相互作用是否可以映射到蚊子基因组中的离散位点，并记录它们的遗传结构。我们开发了一种创新的遗传作图策略，使用实验暴露于来自人类患者的两种登革热病毒血清型的遗传不同分离株的远交蚊子家族来调查G×G相互作用。在蚊子基因组的多个区域中检测到与载体能力指数相关的遗传位点。重要的是，基因型和表型之间的相关性是病毒分离株特异性在这些位点中的几个，表明G×G相互作用。与G×G互作相关的标记所解释的表型变异比例较高（7.8%~ 16.5%），与大效应寄主遗传因素相一致。我们的数据表明，登革热病毒和蚊子载体之间的G×G相互作用可以分配给蚊子基因组的物理区域，其中一些区域对表型有很大影响。这一发现确立了在自然系统中无脊椎动物与其病原体之间特定相互作用的有形宿主遗传因素的存在。未发现的基因位点的精细定位将阐明蚊病毒特异性的分子机制。无脊椎动物宿主-病原体相互作用的结果通常取决于宿主和病原体基因型的特定配对。这种遗传特异性挑战了我们目前对无脊椎动物对病原体的抗性的理解，因为它与已知的无脊椎动物防御机制的有限区分能力形成对比。然而，这种观察到的特异性背后的遗传因素仍然难以捉摸，质疑它们的存在。在这项研究中，我们开发了一种创新的策略来定位蚊子埃及伊蚊基因组中的因子，这些因子控制与登革热病毒的特异性相互作用。我们使用来自泰国自然种群的大型蚊子家族，我们用从生活在同一地区的人类患者中获得的病毒分离株进行实验性攻击。我们确定了蚊子基因组的几个区域，这些区域控制与登革病毒的特异性相互作用，并对观察到的载体能力的变化做出了重大贡献。我们的研究建立了有形的主机遗传因素的存在下，无脊椎动物和它们的病原体之间的特定相互作用在一个自然系统，是有关人类健康。这是确定昆虫-病毒相互作用遗传特异性机制的关键一步。
Specific interactions between host genotypes and pathogen genotypes (G×G interactions) are commonly observed in invertebrate systems. Such specificity challenges our current understanding of invertebrate defenses against pathogens because it contrasts the limited discriminatory power of known invertebrate immune responses. Lack of a mechanistic explanation, however, has questioned the nature of host factors underlying G×G interactions. In this study, we aimed to determine whether G×G interactions observed between dengue viruses and their Aedes aegypti vectors in nature can be mapped to discrete loci in the mosquito genome and to document their genetic architecture. We developed an innovative genetic mapping strategy to survey G×G interactions using outbred mosquito families that were experimentally exposed to genetically distinct isolates of two dengue virus serotypes derived from human patients. Genetic loci associated with vector competence indices were detected in multiple regions of the mosquito genome. Importantly, correlation between genotype and phenotype was virus isolate-specific at several of these loci, indicating G×G interactions. The relatively high percentage of phenotypic variation explained by the markers associated with G×G interactions (ranging from 7.8% to 16.5%) is consistent with large-effect host genetic factors. Our data demonstrate that G×G interactions between dengue viruses and mosquito vectors can be assigned to physical regions of the mosquito genome, some of which have a large effect on the phenotype. This finding establishes the existence of tangible host genetic factors underlying specific interactions between invertebrates and their pathogens in a natural system. Fine mapping of the uncovered genetic loci will elucidate the molecular mechanisms of mosquito-virus specificity. The outcome of invertebrate host-pathogen interactions often depends on the specific pairing of host and pathogen genotypes. This genetic specificity challenges our current understanding of invertebrate resistance to pathogens because it contrasts the limited discriminatory power of known invertebrate defense mechanisms. However, genetic factors underlying this observed specificity have remained elusive, questioning their very existence. In this study, we developed an innovative strategy to localize factors in the genome of the mosquito Aedes aegypti that govern specific interactions with dengue viruses. We used large mosquito families derived from a natural population in Thailand that we experimentally challenged with virus isolates obtained from human patients living in the same area. We identified several regions of the mosquito genome that control specific interactions with dengue viruses and contribute significantly to the observed variation in vector competence. Our study establishes the existence of tangible host genetic factors underlying specific interactions between invertebrates and their pathogens in a natural system that is relevant to human health. This represents a critical step towards identification of mechanisms underlying the genetic specificity of insect-virus interactions.
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作者：
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