Kinesin-mediated transport of Marek's disease virus

马立克氏病是一种致命的、高度传染性的肿瘤性疾病，影响着鸡。它是由一种名为加利德疱疹病毒-2或马立克氏病病毒(MDV)的甲型疱疹病毒引起的。病毒的发病机制可以通过探索病毒与宿主的相互作用来确定，这将使未来能够采取可能阻止MDV传播的干预措施。因此，该项目旨在揭示MDV的细胞内运输和贩运。病毒传播到细胞核并在那里复制形成病毒衣壳，这些衣壳将通过内质网和高尔基体外流以获得包膜，然后返回质膜感染其他邻近细胞。病毒本身太大，不能被动地通过细胞质(直径200-300纳米)扩散，而是利用宿主的细胞骨架和马达蛋白进行细胞运输。已有研究表明，动力蛋白和Kinesin-3家族的马达在MDV的运输中起重要作用。因此，该项目的目标是通过利用邻近依赖的生物素化和质谱学建立与这些马达蛋白相互作用的病毒蛋白，从而确定MDV与马达蛋白的相互作用。此外，还将研究病毒候选蛋白与Kinesin尾巴的结合，以绘制Kinesin和病毒蛋白的相互作用面。将探索缺乏病毒结合位点的马达蛋白截断，以及可能限制MDV传播和提高肉类产量的鸡的马达突变。

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.