Structure function analysis of the Dengue virus capsid protein.

登革热是人类最重要的蚊媒病毒性疾病，全球每年有5000-1亿人感染登革热。感染登革热病毒通常会导致登革热，一种轻微的流感？就像生病一样。然而，在某些情况下，患者可能会出现称为登革出血热/登革休克综合征(DHF/DSS)的严重、可能致命的并发症。本课题旨在研究登革病毒衣壳蛋白在病毒生命周期中的功能及其在疾病过程中的可能作用，探讨登革病毒衣壳蛋白在病毒生命周期中的作用。登革热病毒颗粒只由三种蛋白质的多个副本组成。含有两种表面蛋白的脂膜围绕着由衣壳蛋白和病毒RNA基因组组成的核心。除了在病毒颗粒的形成中发挥作用外，在宿主细胞核中也发现了衣壳蛋白，在那里它有可能扰乱宿主细胞的过程。我们将利用有关衣壳蛋白三维结构的最新信息，结合病毒基因组的基因工程，确定衣壳蛋白对病毒生命周期至关重要的区域。通过确定C蛋白的这些区域在病毒生命周期中的功能，我们将增加我们对登革热病毒复制和疾病的理解，并提供可用于开发新型登革热疫苗和抗病毒化合物的知识。这项调查的结果也将与相关的黄病毒相关，如西尼罗河病毒、黄热病病毒、壁虱传播病毒和日本脑炎病毒，这些病毒会在世界范围内造成公共卫生问题。我们积极鼓励布里斯托尔大学的工作人员向公众宣传他们的研究结果。大学的研究成果通过出版物《Re：Search》中的文章向公众传播，并在社区中广泛分发，并通过组织向公众开放的研究研讨会。

Dengue is the most important mosquito-borne viral disease of humans with 50-100 million people infected annually worldwide. Dengue virus infection usually results in dengue fever, a mild ?flu? like illness. However, in some cases, patients may develop severe, potentially fatal complications known as dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Despite intensive research over recent years, the disease processes leading to DHF/DSS are still poorly understood and there is neither a safe and effective vaccine nor suitable anti-viral treatments to control dengue disease.This project aims to study the function/s of the dengue virus capsid protein in the virus lifecycle and its possible contribution to disease processes. Dengue virus particles consist of multiple copies of only three proteins. A lipid membrane containing two surface proteins surrounds an inner core consisting of the capsid protein and the viral RNA genome. Aside from its role in the formation of the virus particle, the capsid protein has also been found in the host cell nucleus where it has the potential to disturb host cell processes. We will use recent information about the three dimensional structure of the capsid protein, in combination with genetic engineering of the viral genome, to identify regions of the capsid protein essential to the virus lifecycle. By determining how these regions of the C protein function in the virus lifecycle, we will increase our understanding of dengue virus replication and disease, and provide knowledge that can be used to develop novel dengue vaccines and antiviral compounds. The results of this investigation will also be relevant to related flaviviruses such as West Nile virus, Yellow fever virus and tick-borne and Japanese encephalitis viruses which cause public health problems worldwide.Staff at the University of Bristol are actively encouraged to communicate the results of their research to the general public. The results of University research is disseminated to the general public through articles in the publication ?re:search?, widely distributed in the community and by the organisation of research seminars open to the general public.