Characterisation of novel virus-host cell interactions essential for herpes simplex virus envelopment

所有病毒都生长在构成身体的细胞内，制造数以千计的自身副本，然后传播给新的个体。为了做到这一点，他们劫持了细胞机器，将它们的单个组件组合在一起，组装成新的病毒，并释放这些病毒，使它们能够感染新的细胞。包括人类免疫缺陷病毒、流感病毒和埃博拉病毒在内的各种人类病毒被包裹在一种名为信封的特殊膜外套中，这种膜是从细胞内现有的膜中提取的。没有这些包膜，病毒就会死亡，因此阻止它们形成的能力是杀死病毒感染的一个现实和新的靶点。这项提议旨在以一种这样的包膜病毒-人类单纯疱疹病毒(HSV)-发现其包膜形成所需的细胞机器。单纯疱疹病毒是一种经常被忽视的人类感染，但它会导致重大疾病，每年感染2400万人，并导致相当大的发病率和死亡率。我们的目标是使用单纯疱疹病毒作为病毒如何形成包膜的模型，并研究包膜形成的各个步骤，以揭示必要的细胞和病毒成分。然而，像所有的病毒一样，单纯疱疹病毒的直径很小--直径只有万分之一毫米--如果没有尖端技术的帮助，是不可能看到的。因此，我们将使用我们设计的病毒，当我们用专业显微镜观察它们时，它们会发出荧光，并将跟踪它们在单细胞内部的移动。在正常情况下，传播病毒的延时电影将被捕获，并与在单个细胞或病毒部分缺失的细胞中捕获的电影进行比较。最后，我们将使用最先进的显微镜深入观察受感染的细胞，并在单个病毒组装在一起时产生高度放大的图片。通过这种方式，我们的目标是确定所需的机器的构建块。我们的发现将突出HSV1包膜形成所涉及的细胞和病毒成分。他们还将提供信息，帮助了解其他人类病毒如何利用细胞活动。最终，它们将导致开发出阻断病毒包膜的新药--可能适用于多种病毒的药物。我们的发现将有益于全球人口的健康和福祉，并将对单纯疱疹病毒病和其他病毒感染患者的痛苦以及这些感染给英国和其他地区的医疗服务带来的成本产生重大影响。

All viruses grow inside the cells that make up the body, manufacturing thousands of copies of themselves that can go on to spread to new individuals. To do this, they hijack cellular machinery to bring together their individual components, assemble them into new viruses, and release these viruses, making them available to infect new cells. A wide range of human viruses, including human immunodeficiency virus, influenza virus and ebola virus are enwrapped in a special membrane coat called an envelope, which is picked up from existing membranes within the cell. Without these envelopes, the viruses are dead, so the ability to block their formation is a realistic and novel target for killing virus infection.This proposal aims to take one such enveloped virus - the human herpesvirus herpes simplex virus (HSV) to discover the cellular machines that are required for its envelope formation. HSV is an often-disregarded human infection that nonetheless causes significant disease, infecting 24 million annually, and resulting in considerable morbidity and mortality. We aim to use HSV as a model for how viruses make their envelopes, and investigate the individual steps of envelope formation to uncover essential cellular and viral components. However, like all viruses, HSV is minuscule - one 10,000th of a millimetre in diameter - and impossible to see without the help of cutting edge technology. So we will use viruses that we have engineered to shine fluorescently when we look at them with specialist microscopes, and will track their movement through the inside of single cells. Time-lapse movies of travelling virus will be captured under normal conditions and compared to movies captured in cells where individual cell or virus parts are missing. Finally, we will use state-of-the-art microscopes to look deep inside infected cells and produce highly magnified pictures of single viruses as they put themselves together. In this way we aim to identify the building blocks of the machines that are required. The discoveries that we make will highlight cellular and virus components involved in HSV1 envelope formation. They will also provide information to help understand how other human viruses take advantage of cellular activities. Ultimately, they will lead to the development of new drugs to block the virus envelope - drugs that may be applicable to a wide range of viruses. Our discoveries will benefit the health and wellbeing of the global population and will have a significant impact on the suffering of patients with HSV disease and other virus infections, and the cost of these infections to the health service in the UK and beyond.