Analysis of Dengue virus NS5 protein - host cell interactions.

登革病毒(DENV)是一种蚊媒黄病毒，可引起最重要的节肢动物传播的人类病毒性疾病。登革热疾病的范围从轻微发烧到可能致命的登革出血热/休克综合征(登革出血热/休克综合征)。据估计，每年至少发生5,000万登革热感染和250000例登革出血热病例。DHF的特点是血管通透性增加，这被认为是由免疫介导的。我们目前对登革热疾病的了解有限，目前还没有疫苗或抗病毒治疗来控制登革热的传播。我们的研究旨在了解登革热病毒是如何复制和致病的。DENV NS5蛋白已被发现是病毒复制所必需的，也是抗病毒药物开发的重要靶点。最近的证据还表明，NS5蛋白可能在促进疾病方面发挥了作用。我们打算研究NS5如何与宿主细胞相互作用来改变宿主细胞的过程，定义涉及的NS5蛋白的区域，并确定这些特征是否对不同的DENV毒株是共同的。通过确定单个DENV蛋白如何调节宿主细胞过程，我们将增加对DENV疾病的理解。这些知识可用于开发迫切需要的改进的DENV疫苗和抗病毒药物。此外，本申请中提出的研究可能与我们对免疫系统如何发挥作用以控制微生物疾病的一般理解有关。

Dengue virus (DENV) is a mosquito borne flavivirus that causes the most important arthropod-borne viral disease of humans. Dengue disease ranges from mild fever to the potentially fatal dengue haemorrhagic fever/ shock syndromes (DHF/DSS). It is estimated that at least 50 million dengue infections and 250000 cases of DHF occur annually. DHF is characterised by an increase in vascular permeability, which is believed to be immune mediated. Our current understanding of dengue disease is limited and there are no vaccines or antiviral treatments in use to control the spread of DENV.Our research is aimed at understanding how DENV replicates and causes disease. The DENV NS5 protein has been found to be essential for replication of the virus and is an important target for antiviral drug development. Recent evidence also suggests that the NS5 protein may play a role in promoting disease. We intend to investigate how the NS5 interacts with the host cell to alter host cell processes, defining the regions of the NS5 protein involved and determining whether these features are common to different strains of DENV.By determining how individual DENV proteins modulate host cell processes, we will increase our understanding of DENV disease. This knowledge can be used to develop improved DENV vaccines and antiviral agents that are urgently needed. In addition, the research proposed in this application is potentially relevant to our general understanding of how the immune system functions to control microbial disease.