Evasion of antiviral responses in the host cell nucleus

了解病毒在感染细胞时如何被检测到的基本过程，以及细胞用来对抗这种病毒的防御机制，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宿主细胞核中启动和/或起作用的过程。这项研究试图了解我们已经发现的一种新的途径，通过这种途径，疱疹病毒可以在感染细胞的细胞核内逃避抗病毒反应。疱疹病毒是高度流行的动物病原体，在马、牛、猪和家禽养殖业中造成重大疾病和经济损失。人类疱疹病毒还可能导致严重或危及生命的疾病，特别是在免疫抑制的人中，并被认为增加了多发性硬化症和阿尔茨海默病的风险。疱疹病毒感染是终生的--在最初的“一次”感染之后，这些病毒对其宿主建立潜伏感染，例如在神经细胞中，通常在宿主的一生中反复发生重新激活，病毒从其藏身之处出现，引起“二次”感染(例如，唇疱疹)，并传播到新的宿主。由于疱疹病毒感染造成的高疾病负担，显然需要开发新的和改进的抗病毒药物和疫苗来治疗动物和人类的这些病毒感染。这项研究的重点是揭示我们最近发现的新途径的细节，通过这些途径，疱疹病毒可以抵消细胞中的宿主防御。这条此前未知的途径涉及两种病毒蛋白的复合体，其中一种是保守的蛋白质“激酶”，这种酶通过将磷酸盐分子连接到其他蛋白质上来改变它们的功能。我们是否将使用最先进的技术来了解在疱疹病毒感染期间，这种病毒蛋白复合体是如何、为什么以及在哪里针对和修改特定的细胞蛋白的。重要的是，这项研究将提供有关有效对抗多种不同病毒的抗病毒途径的新的重要知识。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，这将为开发新的和改进的抗击疱疹病毒和许多其他重要病毒的方法奠定基础，这些病毒会在世界各地造成重大的动物和人类疾病。

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.