Rabies virus maintenance in bat populations

狂犬病病毒在蝙蝠种群中的维持

• 批准号: 8066429
• 负责人: April Dawn Davis
• 金额: $ 10.55万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8066429
• 关键词: 15 year old; Address; Adverse effects; Aerosols; American; Animals; Antibodies; Area; Brown Fat; Canis familiaris; Cessation of life; Chiroptera; Clinical; Collaborations; Data; Development; Diagnostic; Disease; Disease Outbreaks; Ecology; Environment; Event; Excretory function; Exposure to; Foxes; Glycoproteins; Goals; Hair; Health; Health Care Costs; Hibernation; Human; Immune response; Immune system; Immunity; Incidence; Infection; Intervention; Intramuscular; Investigation; Knowledge; Laboratories; Lead; Lyssavirus; Maintenance; Mammals; Mephitidae; Methods; Molecular Biology; New York; Persons; Play; Population; Prevalence; Production; Prophylactic treatment; Public Health; Rabies; Rabies virus; Raccoons; Recording of previous events; Recovery; Reporting; Research; Rhabdoviridae; Risk; Role; Route; Silver; St. Louis Encephalitis Virus; Temperature; Therapeutic; United States; Variant; Viral; Viral Pathogenesis; Virulence; Virus; Virus Diseases; Zoonoses; base; cell type; cost; effective therapy; experience; improved; infectious disease model; insight; neutralizing antibody; novel; public health research; theories; tissue tropism; transmission process; vector; viral RNA

DESCRIPTION (provided by applicant): Rabies virus (Rhabdoviridae: lyssavirus) is a highly pathogenic virus capable of infecting all mammalian species. Rabies is a unique virus - almost invariably fatal, yet preventable. Rabies treatment is highly effective if treatment occurs early. Once signs of clinical illness appear, treatment is considerably less effective, and death usually occurs within two weeks. Rabies is one of the oldest known viral diseases in history, emerging approximately 11,000 years ago possibly as a viral disease in bats (Badrain and Tordo, 2001). If this hypothesis is correct, it is likely that virus-host adaptation has occurred between rabies virus and bats over the past 11,000 years. In the United States, large scale rabies outbreaks have been reported in other vector species such as dogs, skunks, raccoons, and foxes. However, to date, rabies outbreaks have not occurred in bat populations. Contrary to widespread misconception, rabies appears to be maintained in low levels within bat populations ranging from 0.2% to 5.5% (Trimarchi and Debbie, 1977). It is likely that multiple factors influence the ability of rabies virus to be maintained in bat populations, including the circulating rabies virus variant, the homologous (host) species, and the host's ecological niche. Unlike many other viral zoonoses, bat rabies virus variants are typically associated with a distinct species of bat, thus we will refer to these variants as homologous rabies virus variants (Hughes et. al., 2005, Smith, 2002). Interspecies spill-over of rabies virus variants have been reported and are referred to as heterologous virus variants infections. Rabies virus over wintering in bats has been suggested as a method of rabies maintenance in hibernating bat populations (Calisher, 2008), and previous studies have demonstrated that other viruses, such as St. Louis encephalitis virus, may overwinter in bats (Calisher, 2008, Sulkin and Allen, 1974). However, the role of hibernation and maintenance of viral infections in bats have not been well studied. The proposed research will address two major questions, 1) Is the maintenance of rabies virus determined by bat species or the rabies virus variant to which the bat is exposed, and 2) What impact does hibernation have on the maintenance of rabies virus? We will focus on three major studies to provide the basis for determining how rabies virus is maintained in wild bat populations: 1) We will compare the clinical illness in bats exposed to a homologous and heterologous rabies virus variant; 2) We will examine the immune response following inoculation with a homologous or heterologous rabies virus variant; and 3) We will elucidate the role that hibernation plays in maintenance of rabies virus. Three species of bats will be included in this proposal: big brown bats (Eptesicus fuscus), little brown bats (Myotis spp), and silver hair bats (Lasionycteris noctivagans). Novel aspects of this study include the investigation of homologous and heterologous rabies virus variants in bats as well as the effect of hibernation on rabies virus maintenance in bats. The overall aim of this proposal is to further our understanding of the interaction between rabies virus and its chiropteran host. In this proposal we outline studies to elucidate the role of the immune system and ecological factors that are unique to bats and determine how they relate to the maintenance of rabies in bat populations. The public health significance of rabies is indisputable since clinical infection generally results in death. This set of studies will provide us with a better understanding of how rabies virus is maintained in the most important rabies vector in the U.S. as well as elucidate the importance of spill over events between bat species. This project will lead to a better understanding of rabies virus maintenance in bat populations and its impact on novel hosts. This project is important to public health as bat rabies variants are capable of infecting, adapting, and spreading in heterologous bat species and terrestrial mammal populations. States with terrestrial rabies have a higher incidence of rabies exposure and increased use of anti-rabies therapeutics. Post exposure prophylaxis should be given as soon as possible following contact with a potentially rabid animal. It is expensive, and it is known to cause significant side effects. Completion of the studies described in this proposal will provide data integral to infectious disease modeling and improve our knowledge of the public health risks associated with bat rabies.

描述（由申请方提供）：狂犬病病毒（弹状病毒科：狂犬病病毒属）是一种能够感染所有哺乳动物物种的高致病性病毒。狂犬病是一种独特的病毒--几乎总是致命的，但可以预防。狂犬病治疗是非常有效的，如果治疗发生在早期。一旦出现临床疾病的迹象，治疗的效果就大大降低，通常在两周内死亡。狂犬病是历史上已知的最古老的病毒性疾病之一，大约在11，000年前出现，可能是蝙蝠的病毒性疾病（Badrain和Tordo，2001）。如果这一假设是正确的，那么在过去的11,000年里，狂犬病病毒和蝙蝠之间很可能发生了病毒宿主适应。在美国，已报告在其他病媒物种如狗、臭鼬、浣熊和狐狸中发生大规模狂犬病暴发。然而，到目前为止，狂犬病还没有在蝙蝠种群中爆发。与普遍存在的误解相反，蝙蝠种群中狂犬病似乎维持在0.2%至5.5%的低水平（Trimarchi和Debbie，1977年）。可能有多种因素影响狂犬病病毒在蝙蝠种群中维持的能力，包括流行的狂犬病病毒变体，同源（宿主）物种和宿主的生态位。与许多其他病毒性人畜共患病不同，蝙蝠狂犬病病毒变异体通常与不同种类的蝙蝠相关，因此我们将这些变异体称为同源狂犬病病毒变异体（Hughes et.例如，Smith，2002）。已报告狂犬病病毒变异体的种间溢出，称为异源病毒变异体感染。狂犬病病毒在蝙蝠中越冬被认为是冬眠蝙蝠种群中狂犬病维持的一种方法（Calisher，2008），先前的研究表明，其他病毒，如圣路易斯脑炎病毒，可能在蝙蝠中越冬（Calisher，2008，Sulkin和艾伦，1974）。然而，蝙蝠冬眠和维持病毒感染的作用还没有得到很好的研究。拟议的研究将解决两个主要问题，1）狂犬病病毒的维持是由蝙蝠物种或蝙蝠暴露的狂犬病病毒变体决定的，2）冬眠对狂犬病病毒的维持有什么影响？我们将集中在三个主要的研究，以提供基础，以确定如何狂犬病病毒是维持在野生蝙蝠种群：1）我们将比较临床疾病的蝙蝠暴露于同源和异源狂犬病病毒变异体; 2）我们将检查免疫反应后接种同源或异源狂犬病病毒变异体;（3）阐明冬眠在狂犬病毒维持中的作用。三种蝙蝠将包括在这一建议中：大棕蝙蝠（Eptesicus fuscus），小棕蝙蝠（鼠耳蝠属），和银毛蝙蝠（Lasionycteris spantivagans）。这项研究的新方面包括调查蝙蝠中的同源和异源狂犬病病毒变异体以及冬眠对蝙蝠中狂犬病病毒维持的影响。本提案的总体目标是进一步了解狂犬病病毒与其翼手目宿主之间的相互作用。在这项提案中，我们概述了研究，以阐明免疫系统和生态因素的作用，是独特的蝙蝠，并确定它们如何与蝙蝠种群的狂犬病的维护。狂犬病的公共卫生意义是无可争议的，因为临床感染通常会导致死亡。这一系列研究将使我们更好地了解狂犬病病毒如何在美国最重要的狂犬病载体中维持，并阐明蝙蝠物种之间溢出事件的重要性。该项目将导致更好地了解狂犬病病毒在蝙蝠种群中的维持及其对新宿主的影响。该项目对公共卫生很重要，因为蝙蝠狂犬病变种能够在异源蝙蝠物种和陆生哺乳动物种群中感染、适应和传播。有陆地狂犬病的州狂犬病暴露的发生率较高，抗狂犬病治疗的使用增加。接触可能患有狂犬病的动物后，应尽快进行暴露后预防。它是昂贵的，并且已知会引起显著的副作用。完成本提案中描述的研究将为传染病建模提供不可或缺的数据，并提高我们对蝙蝠狂犬病相关公共卫生风险的认识。