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Viruses in connectomics: Viral transneuronal tracers and genetically modified recombinants as neuroscience research tools.
Journal of Neuroscience Methods ( IF 2.7 ) Pub Date : 2020-08-21 , DOI: 10.1016/j.jneumeth.2020.108917
Gabriella Ugolini 1
Affiliation  

Connectomic studies have become ‘viral’, as viral pathogens have been turned into irreplaceable neuroscience research tools. Highly sensitive viral transneuronal tracing technologies are available, based on the use of alpha-herpesviruses and a rhabdovirus (rabies virus), which function as self-amplifying markers by replicating in recipient neurons. These viruses highly differ with regard to host range, cellular receptors, peripheral uptake, replication, transport direction and specificity. Their characteristics, that make them useful for different purposes, will be highlighted and contrasted. Only transneuronal tracing with rabies virus is entirely specific. The neuroscientist toolbox currently include wild-type alpha-herpesviruses and rabies virus strains enabling polysynaptic tracing of neuronal networks across multiple synapses, as well as genetically modified viral tracers for dual transneuronal tracing, and complementary viral tools including defective and chimeric recombinants that function as single step or monosynaptically restricted tracers, or serve for monitoring and manipulating neuronal activity and gene expression. Methodological issues that are crucial for appropriate use of these technologies will be summarized. Among wild-type and genetically engineered viral tools, rabies virus and chimeric recombinants based on rabies virus as virus backbone are the most powerful, because of the ability of rabies virus to propagate exclusively among connected neurons unidirectionally (retrogradely), without affecting neuronal function. Understanding in depth viral properties is essential for neuroscientists who intend to exploit alpha-herpesviruses, rhabdoviruses or derived recombinants as research tools. Key knowledge will be summarized regarding their cellular receptors, intracellular trafficking and strategies to contrast host defense that explain their different pathophysiology and properties as research tools.



中文翻译:

连接组学中的病毒:病毒跨神经示踪剂和转基因重组体作为神经科学研究工具。

由于病毒病原体已成为不可替代的神经科学研究工具,因此连通性研究已成为“病毒”。基于α-疱疹病毒和弹状病毒(狂犬病病毒)的使用,可以使用高度敏感的病毒跨神经示踪技术,它们通过在受体神经元中复制而充当自我扩增标记。这些病毒在宿主范围,细胞受体,外周摄取,复制,转运方向和特异性方面存在很大差异。它们的特性(使它们可用于不同目的)将被突出和对比。只有狂犬病病毒的跨神经示踪是完全特异性的。目前,神经科学家工具箱中包含野生型α疱疹病毒和狂犬病病毒株,可以跨多个突触对神经元网络进行多突触追踪,以及用于双跨神经元追踪的转基因病毒示踪剂,以及互补的病毒工具,包括有缺陷和嵌合的重组体,它们可作为单步或单突触限制示踪剂发挥作用,或用于监测和操纵神经元活性和基因表达。将总结对于适当使用这些技术至关重要的方法论问题。在野生型和基因工程病毒工具中,狂犬病病毒和基于狂犬病病毒作为病毒骨架的嵌合重组体功能最强大,因为狂犬病病毒能够在连接的神经元之间单向(逆行)传播,而不会影响神经元功能。对于打算利用α疱疹病毒的神经科学家来说,深入了解病毒特性至关重要,弹状病毒或衍生重组体作为研究工具。将总结有关其细胞受体,细胞内运输和对比宿主防御的策略的关键知识,这些知识解释了它们作为研究工具的不同病理生理和特性。

更新日期:2020-09-09
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