Rabies virus maintenance in bat populations

描述(申请人提供)：狂犬病病毒(横纹病毒科：溶血病毒)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，狂犬病的治疗是非常有效的。一旦出现临床疾病的迹象，治疗效果就会大大降低，死亡通常会在两周内发生。狂犬病是历史上已知的最古老的病毒性疾病之一，大约在11000年前出现，可能是蝙蝠的一种病毒性疾病(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，其他媒介物种如狗、臭鼬、浣熊和狐狸也爆发了大规模狂犬病疫情。然而，到目前为止，狂犬病还没有在蝙蝠种群中爆发。与普遍的误解相反，狂犬病似乎在蝙蝠种群中维持在从0.2%到5.5%的低水平(Trimarchi和Debbie，1977)。狂犬病病毒在蝙蝠种群中维持的能力可能受到多种因素的影响，包括流行的狂犬病病毒变异株、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，蝙蝠狂犬病病毒变种通常与不同种类的蝙蝠有关，因此我们将这些变种称为同源狂犬病病毒变种(Hughes et.等人，2005年，史密斯，2002年)。狂犬病病毒变种的种间溢出已有报道，并被称为异源病毒变种感染。狂犬病病毒在蝙蝠中越冬被认为是维持冬眠蝙蝠种群狂犬病的一种方法(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Allen，1974)。然而，蝙蝠的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接触的狂犬病病毒变种决定的，2)冬眠对狂犬病病毒的维持有什么影响？我们将重点进行三项主要研究，为确定狂犬病病毒如何在野生蝙蝠种群中维持提供基础：1)我们将比较暴露于同源和异种狂犬病病毒变种的蝙蝠的临床疾病；2)我们将检测接种同源或异种狂犬病病毒变种后的免疫反应；以及3)我们将阐明冬眠在狂犬病病毒维持中所起的作用。这项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 Noctivan Ans)。这项研究的新方面包括调查蝙蝠中狂犬病病毒的同源和异源变异，以及冬眠对蝙蝠狂犬病病毒维持的影响。这项建议的总体目的是加深我们对狂犬病病毒与其翼手目宿主之间的相互作用的了解。在这项建议中，我们概述了一些研究，以阐明蝙蝠特有的免疫系统和生态因素的作用，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媒介中维持的，并阐明蝙蝠物种之间事件溢出的重要性。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。这个项目对公众健康很重要，因为蝙蝠狂犬病的变种能够在异种蝙蝠和陆地哺乳动物种群中感染、适应和传播。有陆源性狂犬病的州有更高的狂犬病暴露发生率和更多的抗狂犬病治疗药物的使用。接触潜在的狂犬病动物后，应尽快采取暴露后预防措施。它价格昂贵，而且众所周知会造成严重的副作用。完成这项建议中描述的研究将提供传染病建模所必需的数据，并提高我们对与蝙蝠狂犬病相关的公共卫生风险的了解。

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.