GPI anchored forms of the dengue virus NS1 protein: production and role in pathogenesis

登革热病毒由蚊子携带，感染世界各地数百万人，特别是在东南亚、中美洲和南美洲、非洲的热带国家，最近在澳大利亚（北昆士兰州和新台币）。没有疫苗或药物可用于预防或治疗感染，其特征是严重的疾病，涉及炎症和发烧，有时可能是致命的。这项研究的重点是一种不寻常的形式的登革热病毒蛋白（称为NS 1），我们已经确定。我们计划研究这种蛋白质在更严重和往往致命的登革热感染形式（登革出血热和登革休克综合征）中所起的作用。在这些更严重和危及生命的登革热形式中，这些患者的血管变得渗漏。据认为，这是由受感染细胞分泌某些化学物质（细胞因子）引起的。我们已经证明，登革热感染的人类细胞，其表面具有不寻常的NS 1蛋白形式，能够被抗体激活。抗体是由人体产生的蛋白质，用于对抗感染。我们的目标是研究细胞因子是否从以这种方式激活的受感染的人血细胞中分泌，以及这些细胞因子是否会导致血管渗漏。我们还将研究病毒如何在病毒感染的两种宿主物种中产生这种NS 1变体形式;蚊子和人类。这些研究将增加我们对登革病毒感染的了解，并将提供有关这种不寻常形式的登革病毒蛋白NS 1在登革热、登革出血热和登革休克综合征的严重形式中所起作用的有价值的信息。

Dengue viruses are carried by mosquitoes and infect millions of people around the world, particularly in tropical countries of SE Asia, Central and South America, Africa and recently in Australia (North Queensland and NT). There is no vaccine or drug available for preventing or treating the infections, which are characterised by severe illness that involves inflammation and fevers that can sometimes be fatal. This study focuses on an unusual form of a dengue virus protein (called NS1) which we have identified. We plan to study the role that this protein plays in the more severe and often fatal forms of dengue infection (dengue haemorrhagic fever and dengue shock syndrome). In these more severe and life threatening forms of dengue the blood vessels of these patients become leaky. It is thought that this is caused by the secretion of certain chemicals (cytokines) from infected cells. We have shown that dengue infected human cells, which have the unusual form of NS1 protein on their surface, are capable of being activated by antibodies. Antibodies are proteins which are produced by the human body to fight infection. We aim to study whether cytokines are secreted from infected human blood cells activated in this way and whether these cytokines cause blood vessels to become leaky. We will also study how the virus produces this variant form of NS1 in the two host species that the virus infects; mosquito and human. These studies will increase our understanding of dengue virus infection and will provide valuable information concerning the role that this unusual form of the degue virus protein NS1 plays in the severe forms of dengue fever; dengue haemorrhagic fever and dengue shock syndrome.