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Kinesin-mediated transport of Marek's disease virus

驱动蛋白介导的马立克氏病病毒运输

基本信息

批准号：
2391881
负责人：
金额：
--
依托单位：
University of Warwick
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2391881
关键词：
Kinesin mediated transport Marek disease

项目摘要

Marek's disease is a fatal, highly contagious, neoplastic disease affecting chickens. It is caused by an alphaherpesvirus called Gallid herpesvirus-2 or Marek's Disease Virus (MDV). Pathogenesis of the virus can be characterised by exploring virus-host interactions which will enable future interventions that could impede MDV transmission. Therefore, the project aims to uncover the intracellular transport and trafficking of MDV. The virus travels to the nucleus and replicates where it will form viral capsids that will egress via the ER and Golgi for envelopment, then will return to the plasma membrane to infect other neighbouring cells. The virus itself is too large to passively diffuse through the cytoplasm (with a diameter of 200-300 nm), and instead exploits the host's cytoskeleton and motor proteins for cellular transport. It has been implicated that dynein and motors of the kinesin -3 family are instrumental in MDV transport. Therefore, the project will aim to identify how MDV interacts with motor proteins by establishing viral proteins that interact with these motor proteins using proximity-dependent biotinylation and mass spectrometry. As well as this, the binding of the viral candidate proteins with kinesin tails will be investigated to map interaction surfaces on kinesin and viral proteins. Motor protein truncations that lack viral binding sites will be explored and motor mutations in chickens that could potentially limit MDV spread and enhance meat production.

马立克氏病是一种影响鸡的致命的、高度传染性的肿瘤性疾病。它是由称为鸡疱疹病毒-2或马立克氏病病毒（MDV）的α疱疹病毒引起的。病毒的发病机制可以通过探索病毒-宿主相互作用来表征，这将使未来的干预措施能够阻止MDV的传播。因此，该项目旨在揭示MDV的细胞内转运和贩运。病毒行进到细胞核并复制，在那里它将形成病毒衣壳，这些病毒衣壳将通过ER和高尔基体排出以进行复制，然后将返回质膜以感染其他邻近细胞。病毒本身太大，不能被动地通过细胞质扩散（直径为200-300 nm），而是利用宿主的细胞骨架和马达蛋白进行细胞运输。已经暗示动力蛋白和驱动蛋白-3家族的马达在MDV运输中起作用。因此，该项目的目标是通过使用邻近依赖性生物素化和质谱法建立与这些马达蛋白相互作用的病毒蛋白来确定MDV如何与马达蛋白相互作用。除此之外，还将研究病毒候选蛋白与驱动蛋白尾部的结合，以绘制驱动蛋白和病毒蛋白的相互作用表面。缺乏病毒结合位点的马达蛋白截短将被探索，鸡的马达突变可能会限制MDV的传播并提高肉类产量。