Rabies virus maintenance in bat populations

狂犬病病毒在蝙蝠种群中的维持

• 批准号: 8260828
• 负责人: April Dawn Davis
• 金额: $ 10.58万
• 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/8260828
• 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（由申请人提供）：狂犬病毒（Rhabdoviridae: lyssavvirus）是一种高致病性病毒，能够感染所有哺乳动物物种。狂犬病是一种独特的病毒——几乎总是致命的，但可以预防。如果及早治疗，狂犬病治疗是非常有效的。一旦出现临床疾病迹象，治疗效果就会大大降低，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11000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，据报道，在狗、臭鼬、浣熊和狐狸等其他媒介物种中也发生了大规模狂犬病暴发。然而，迄今为止，尚未在蝙蝠种群中发生狂犬病暴发。与普遍的误解相反，狂犬病似乎在蝙蝠种群中维持在0.2%至5.5%的低水平（Trimarchi和Debbie， 1977）。可能有多种因素影响狂犬病毒在蝙蝠种群中的维持能力，包括流行的狂犬病毒变体、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，蝙蝠狂犬病毒变体通常与不同种类的蝙蝠有关，因此我们将这些变体称为同源狂犬病毒变体（Hughes等，2005;Smith, 2002）。狂犬病病毒变异的种间溢出已被报道，并被称为异源病毒变异感染。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），以前的研究表明，其他病毒，如圣路易斯脑炎病毒，也可能在蝙蝠中越冬（Calisher, 2008； Sulkin和Allen， 1974）。然而，蝙蝠冬眠和维持病毒感染的作用尚未得到很好的研究。拟开展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种类或蝙蝠所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？我们将重点开展三项主要研究，为确定狂犬病毒在野生蝙蝠种群中的维持机制提供依据：1)比较暴露于同种和异种狂犬病毒变体的蝙蝠的临床疾病；2)我们将检测接种同种或异种狂犬病病毒变体后的免疫反应；3)阐明冬眠对狂犬病毒维持的作用。该提案将包括三种蝙蝠：大棕色蝙蝠（Eptesicus fuscus）、小棕色蝙蝠（Myotis spp）和银毛蝙蝠（Lasionycteris noctivagans）。本研究的新内容包括蝙蝠体内同种和异种狂犬病毒变异的研究，以及冬眠对蝙蝠体内狂犬病毒维持的影响。本研究的总体目的是进一步了解狂犬病毒与其翼类宿主之间的相互作用。在本提案中，我们概述了阐明蝙蝠特有的免疫系统和生态因素的作用的研究，并确定它们如何与蝙蝠种群中狂犬病的维持有关。狂犬病的公共卫生意义是无可争辩的，因为临床感染通常会导致死亡。这组研究将使我们更好地了解狂犬病病毒是如何在美国最重要的狂犬病载体中维持的，并阐明蝙蝠物种之间溢出事件的重要性。该项目将有助于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。该项目对公共卫生具有重要意义，因为蝙蝠狂犬病变体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。存在陆源狂犬病的国家狂犬病暴露发生率较高，抗狂犬病疗法的使用也较多。在接触可能患有狂犬病的动物后，应尽快采取接触后预防措施。它很昂贵，而且已知会引起严重的副作用。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，并提高我们对与蝙蝠狂犬病相关的公共卫生风险的认识。