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

点击翻译按钮获取中文摘要

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.