Australian bat lyssavirus tropism entry and host factor dependence

澳大利亚蝙蝠狂犬病病毒的趋向性进入和宿主因子依赖性

• 批准号: 7670057
• 负责人: CHRISTOPHER C BRODER
• 金额: $ 34.22万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-03 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670057
• 关键词: Address; Animals; Antibodies; Antigens; Area; Australia; Australian bat lyssaviruses; Binding; Cell Culture Techniques; Cells; Cellular biology; Cherry - dietary; Chiroptera; Collaborations; Data; Dependence; Disease; Eligibility Determination; Encephalitis; Family Pteropodidae; Filovirus; Forensic Medicine; Fruit; Genome; Goals; Growth; Health; Henipavirus; Human; Infection; Integration Host Factors; Intervention; Libraries; Lyssavirus; Membrane Fusion; Mononegavirales; Mus; National Institute of Allergy and Infectious Disease; Phage Display; Play; Population; Process; Proteins; Public Health; Queensland; RNA Interference; RNA Viruses; Rabies; Rabies virus; Reagent; Reporter Genes; Research; Research Personnel; Resistance; Rhabdoviridae; Role; Screening procedure; Services; Structure; System; Therapeutic Intervention; Tropism; Vesicular stomatitis Indiana virus; Viral; Virus; Virus Diseases; beta-Lactamase; biodefense; cell type; experience; glycoprotein G; indium arsenide; neutralizing antibody; particle; programs; receptor; therapeutic target; tool; virology

As a group, viruses have played major roles in both the number and significance of newly recognized diseases in both animals and humans. A recent example is Australian Bat Lyssavirus (ABLV). ABLV is a newly recognized rabies virus-related rhabdovirus belonging to the genus Lyssavirus and is an enveloped, single-stranded negative-sense RNA virus with an envelope G glycoprotein that is responsible for attachment, membrane fusion, and infection of host cells. ABLV is categorized in Group I of the NIAID Emerging and Re-emerging Diseases list, one circulating in flying foxes (fruit bats) and another in insectivorous bats. Each caused fatal rabies-like encephalitis in humans but with quite different incubation periods. Previously, we developed successful research programs on the henipaviruses (Hendra and Nipah) in our first support period, and many of the tools and expertise derived from those studies along with our collaborative ties with investigators in Australia now offers us the unique opportunity to initiate a new project within the MARCE-2 renewal. Here, we will address several areas related to ABLV binding, entry and infection of host cells, providing new data on this under-researched emerging virus as well as potentially uncovering new information that may be applicable to other viruses within the Mononegavirales, including the filoviruses (Ebola and Marburg) and the henipaviruses (Hendra and Nipah) - areas in which we are well experienced. We have long standing collaborations with leading investigators in Australia: Dr. Linfa Wang at the CSIRO and Dr. Ina Smith at the Public Health Virology unit of Queensland Health, Forensic and Scientific Services. The overall goal of our project is to understand the binding and infection process of ABLV and to identify viral and host cell targets for developing therapeutic intervention strategies. Specifically, we propose to: 1. Explore and characterize the host cell type and species tropisms of ABLV. 2. Develop and characterize soluble monomeric and trimeric forms of ABLV-G; and isolate and characterize human anti-G Fabs and domain antibody (dAb) using phage-display platforms. 3. We will conduct high-throughput RNAi screening for host cell factors required for ABLV infection and growth in cell culture.

作为一个群体，病毒在新识别的病毒的数量和重要性方面都发挥了重要作用。 动物和人类的疾病。最近的一个例子是澳大利亚蝙蝠狂犬病毒（ABLV）。ABLV是一个 新发现的狂犬病病毒相关弹状病毒属于狂犬病病毒属， 单链负义RNA病毒，具有包膜G糖蛋白，负责 附着、膜融合和宿主细胞的感染。ABLV被归类为NIAID的I组 新出现和重新出现的疾病清单，一种在狐蝠（果蝠）中传播，另一种在 食虫蝙蝠每种病毒都能在人类中引起致命的狂犬病样脑炎，但潜伏期却截然不同 时期以前，我们开发了关于亨德拉病毒和尼帕病毒的成功研究计划。 在我们的第一个支持期，以及从这些研究中获得的许多工具和专业知识沿着我们的 与澳大利亚调查人员的合作关系现在为我们提供了启动新项目的独特机会 在MARCE-2更新中。在这里，我们将讨论与ABLV绑定、进入和 感染宿主细胞，提供了关于这种研究不足的新兴病毒的新数据， 发现可能适用于单负性病毒目中其他病毒的新信息，包括 丝状病毒（埃博拉病毒和马尔堡病毒）和亨德拉病毒和尼帕病毒， 经验丰富。我们与澳大利亚领先的研究人员有着长期的合作关系：王林发博士 CSIRO和昆士兰州卫生、法医和 科学服务。我们的项目的总体目标是了解的绑定和感染过程 ABLV，并确定病毒和宿主细胞的目标，以制定治疗干预策略。具体地说， 我们建议： 1.探索和表征ABLV的宿主细胞类型和种嗜性。 2.开发和表征ABLV-G的可溶性单体和三聚体形式;并分离和 使用噬菌体展示平台表征人抗G Fab和结构域抗体（dAb）。 3.我们将对ABLV所需的宿主细胞因子进行高通量RNAi筛选 感染和细胞培养物中生长。