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

基本信息

批准号：
8233373
负责人：
CHRISTOPHER C BRODER
金额：
$ 34.94万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8233373
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

项目摘要

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，病毒在新认识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病毒（ABLV）。 ABLV 是一个新认识的狂犬病病毒相关弹状病毒属于狂犬病病毒属，是一种有包膜的、单链负义RNA病毒，具有包膜G糖蛋白，负责宿主细胞的附着、膜融合和感染。 ABLV 属于 NIAID 的第一组新发和再发疾病清单，一种在果蝠中传播，另一种在狐蝠中传播食虫蝙蝠。每一种病毒都会引起人类致命的狂犬病样脑炎，但潜伏期却截然不同期间。此前，我们针对亨尼帕病毒（亨德拉病毒和尼帕病毒）开发了成功的研究项目在我们的第一个支持期间，以及从这些研究中获得的许多工具和专业知识以及我们的与澳大利亚研究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 更新范围内。在这里，我们将讨论与 ABLV 绑定、进入和相关的几个领域。感染宿主细胞，提供有关这种尚未充分研究的新兴病毒的新数据以及潜在的发现可能适用于单链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）和亨尼帕病毒（亨德拉病毒和尼帕病毒）——我们擅长的领域经验丰富。我们与澳大利亚领先的研究人员有着长期的合作：Linfa Wang 博士 CSIRO 的博士和昆士兰卫生、法医和公共卫生病毒学部门的 Ina Smith 博士科学服务。我们项目的总体目标是了解 ABLV 并确定病毒和宿主细胞靶点以制定治疗干预策略。具体来说，我们建议： 1. 探索并表征ABLV的宿主细胞类型和种向性。 2. 开发并表征ABLV-G的可溶性单体和三聚体形式；并隔离和使用噬菌体展示平台表征人类抗 G Fab 和域抗体 (dAb)。 3. 我们将对ABLV所需的宿主细胞因子进行高通量RNAi筛选细胞培养物中的感染和生长。