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

登革热病毒 NS1 蛋白的 GPI 锚定形式：产生及其在发病机制中的作用

• 批准号: nhmrc : 102484
• 负责人: Prof Paul Young
• 金额: $ 13.57万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/gpi-anchored-forms-role-pathogenesis/77597
• 关键词: GPI; anchored; forms; dengue; virus

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.

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，以及最近在澳大利亚（北昆士兰和北领地）。目前尚无疫苗或药物可用于预防或治疗感染，其特点是严重疾病，包括炎症和发烧，有时可能致命。这项研究的重点是我们已经鉴定出的一种不寻常形式的登革热病毒蛋白（称为 NS1）。我们计划研究这种蛋白质在更严重且往往致命的登革热感染（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中，这些患者的血管会出现渗漏。人们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表面具有不寻常形式的 NS1 蛋白，能够被抗体激活。抗体是人体产生的对抗感染的蛋白质。我们的目的是研究以这种方式激活的受感染的人类血细胞是否会分泌细胞因子，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 NS1 变异形式；蚊子和人类。这些研究将增加我们对登革热病毒感染的了解，并将提供有关这种不寻常形式的登革热病毒蛋白 NS1 在严重形式的登革热中所起的作用的有价值的信息；登革出血热和登革休克综合征。