Evasion of antiviral responses in the host cell nucleus

逃避宿主细胞核中的抗病毒反应

• 批准号: BB/X014126/1
• 负责人: Colin Crump
• 金额: $ 75.28万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX014126%2F1
• 关键词: Evasion; antiviral; responses; host; cell

Understanding the fundamental processes of how viruses are detected when they infect a cell and the defence mechanisms that cells employ to combat such viruses is crucial for improving the health and wellbeing of humans, animals and plants. Many important host defence pathways rely on processes initiated and/or functioning in the host cell nucleus. This research seeks to understand a new pathway we have discovered by which herpesviruses can evade antiviral responses within the nucleus of infected cells. Herpesviruses are highly prevalent pathogens of animals that cause significant disease and economic losses in the horse, cow, pig and poultry industries. Human herpesviruses can also cause severe or life-threatening disease, especially in immuno-suppressed people, and are thought to increase the risk of multiple sclerosis and Alzheimer's disease. Herpesvirus infections are for life - after the initial 'primary' infection these viruses establish a latent infection of their hosts, for example in nerve cells, which is commonly followed by repeated episodes of reactivation over the lifetime of the host, where the virus emerges from its hiding place to cause 'secondary' infections (e.g. cold sores) and spread to new hosts. Because of the high disease-burden caused by herpesvirus infections, there is a clear need to develop new and improved antiviral drugs and vaccines to treat infections with these viruses in animals and humans.The focus of this research is to uncover the details of the new pathway we have recently discovered by which herpesviruses can counteract host defences in cells. This previously unknown pathway involves a complex of two virus proteins, one of which is a conserved protein "kinase", an enzyme that modifies the function of other proteins by attaching a phosphate molecule to them. Will we use state-of-the-art techniques to understand how, why and where specific cellular proteins are targeted and modified by this virus protein complex during herpesvirus infection. Importantly, this research will provide new and important knowledge about antiviral pathways that are effective against a diverse range of different viruses. The new understanding of how viruses interact with their hosts that we will gain from this research will underpin the development of new and improved ways of fighting herpesviruses, as well as many other important viruses, that cause significant animal and human diseases throughout the world.

了解病毒感染细胞时如何被检测的基本过程以及细胞用于对抗此类病毒的防御机制对于改善人类，动物和植物的健康和福祉至关重要。许多重要的宿主防御途径依赖于在宿主细胞核中启动和/或起作用的过程。这项研究旨在了解我们发现的一种新途径，通过这种途径疱疹病毒可以逃避感染细胞核内的抗病毒反应。疱疹病毒是动物的高度流行的病原体，在马、牛、猪和家禽业中引起显著的疾病和经济损失。人类疱疹病毒也会导致严重或危及生命的疾病，特别是在免疫抑制的人群中，并被认为会增加多发性硬化症和阿尔茨海默病的风险。疱疹病毒感染是终身的-在最初的“原发性”感染后，这些病毒建立了对宿主的潜伏感染，例如在神经细胞中，这通常是在宿主的一生中反复激活的事件，其中病毒从其隐藏的地方出现，引起“继发性”感染（例如唇疱疹）并传播到新的宿主。由于疱疹病毒感染所造成的高疾病负担，有一个明确的需要开发新的和改进的抗病毒药物和疫苗来治疗这些病毒在动物和人类的感染，这项研究的重点是揭示我们最近发现的新途径的细节，疱疹病毒可以抵消宿主细胞的防御。这种以前未知的途径涉及两种病毒蛋白质的复合物，其中一种是保守的蛋白质“激酶”，一种通过将磷酸分子连接到其他蛋白质上来改变其他蛋白质功能的酶。我们将使用最先进的技术来了解在疱疹病毒感染过程中，特定的细胞蛋白质是如何、为什么以及在哪里被这种病毒蛋白质复合物靶向和修饰的。重要的是，这项研究将提供有关抗病毒途径的新的重要知识，这些途径可有效对抗各种不同的病毒。我们将从这项研究中获得对病毒如何与宿主相互作用的新理解，这将支持开发新的和改进的方法来对抗疱疹病毒以及许多其他重要的病毒，这些病毒在世界各地引起重大的动物和人类疾病。