THE ROLE OF CELL SURFACE GLYCOSAMINOGLYCANS IN FLAVIVIRUS BIOLOGY: VIRUS ENTRY, TROPISM, VIRULENCE, AND ANTIVIRALS

细胞表面糖胺聚糖在黄病毒生物学中的作用：病毒进入、趋向性、毒力和抗病毒药物

• 批准号: nhmrc : 366736
• 负责人: A/Pr Mario Lobigs
• 金额: $ 32.92万
• 依托单位: Australian National University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-cell-surface-virulence-antivirals/101499
• 关键词: ROLE; CELL; SURFACE; GLYCOSAMINOGLYCANS; FLAVIVIRUS

The flaviviruses are a group of viruses mostly transmitted by the bite of infected mosquitoes or ticks to vertebrate hosts. They have a world-wide distribution and many flaviviruses are important human and veterinary pathogens. Dengue virus is the most important flavivirus in terms of disease frequency, causing >50 million cases of dengue fever, annually, in tropical and subtropical countries. It has been estimated that 2.5 billion people are at risk of dengue virus infection. Japanese encephalitis virus is the most important causative agent of viral encephalitis in humans; >35,000 cases of Japanese encephalitis occur annually, with 30-50% mortality and frequent life-long neurological impairment among survivors. Murray Valley encephalitis virus is endemic in northern Australia where it gives rise, in most years, to a small number of human cases of sometimes fatal encephalitis. Dengue, Japanese encephalitis, and Murray Valley encephalitis viruses are a threat to human health in Australia. There is wide-spread speculation that climate change will affect the pattern of transmission of vector-borne pathogens; accordingly , the population at risk of flavivirus infection in Australia (and world-wide) may dramatically increase in future years. This project investigates the role of sulfated sugar molecules present abundantly on cellular surfaces in the biology of flaviviruses. It will address how the binding ability of medically important flaviviruses to these sulfated sugars impacts on the efficiency of virus entry into diverse cell types and, in turn, on the virus ability to cause disease. Ultimately, we aim to exploit the affinity of flavivirus particles to the sulfated sugar molecules on cellular surfaces; we will select synthetic mimetics of these sulfated sugars that block virus attachment to cells, and thus may identify antiviral compounds that may find application as therapeutic agents against flaviviral disease.

黄病毒是一组主要通过受感染的蚊子或蜱叮咬传播给脊椎动物宿主的病毒。黄病毒在世界范围内广泛分布，许多黄病毒是重要的人类和兽医病原体。登革病毒是最重要的黄病毒，在疾病频率方面，每年在热带和亚热带国家造成5000万例登革热病例。据估计，有25亿人面临登革热病毒感染的风险。日本脑炎病毒是人类病毒性脑炎最重要的病原体;每年发生35，000例日本脑炎，死亡率为30-50%，幸存者中经常出现终身神经功能障碍。墨累谷脑炎病毒是澳大利亚北方的地方性流行病，在大多数年份，它引起少数有时致命的脑炎病例。登革热、日本脑炎和墨累谷脑炎病毒对澳大利亚的人类健康构成威胁。人们普遍猜测，气候变化将影响病媒传播病原体的传播模式;因此，澳大利亚（和全世界）面临黄病毒感染风险的人口在未来几年可能会急剧增加。该项目研究了黄病毒生物学中大量存在于细胞表面的硫酸化糖分子的作用。它将解决医学上重要的黄病毒与这些硫酸化糖的结合能力如何影响病毒进入不同细胞类型的效率，进而影响病毒引起疾病的能力。最终，我们的目标是利用黄病毒颗粒对细胞表面上的硫酸化糖分子的亲和力;我们将选择这些硫酸化糖的合成模拟物，阻止病毒附着于细胞，从而可能鉴定出可用作黄病毒疾病治疗剂的抗病毒化合物。