Analysis of Dengue virus NS5 protein - host cell interactions.

登革热病毒（DENV）是一种由蚊子传播的黄病毒，可引起人类最重要的节肢动物传播的病毒性疾病。登革热的范围从轻度发热到可能致命的登革出血热/休克综合征（DHF/DSS）。据估计，每年至少发生5000万登革热感染和25万登革出血热病例。DHF的特点是血管通透性增加，这被认为是免疫介导的。我们目前对登革热的了解有限，没有疫苗或抗病毒治疗用于控制登革热病毒的传播。我们的研究旨在了解DENV如何复制并导致疾病。DENV NS5蛋白已被发现对病毒的复制至关重要，并且是抗病毒药物开发的重要靶点。最近的证据也表明NS5蛋白可能在促进疾病中发挥作用。我们打算研究NS5如何与宿主细胞相互作用以改变宿主细胞过程，确定NS5蛋白参与的区域，并确定这些特征是否在不同的DENV菌株中是共同的。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急需的改进的DENV疫苗和抗病毒药物。此外，本应用中提出的研究可能与我们对免疫系统如何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.