Risk of Viral Emergence from Bats

描述（由研究者提供）：新出现的人畜共患病对全球公共卫生和我们的经济构成重大威胁。大多数是由野生动物宿主中出现频率越来越高的病原体引起的（例如黑猩猩的HIV-1，蝙蝠和果子狸的SARS CoV，果蝠的Nipah病毒）。仅这类疾病每年就造成数万人死亡，一些疾病的爆发（如SARS）给全球经济造成了数百亿美元的损失。然而，尽管EID对社会、人口和经济产生了巨大的影响，但我们对这些野生动物人兽共患病如何出现的基本过程的理解，以及开发预防未来出现的预测方法方面，进展甚微。发展预测性和主动性的方法来应对人畜共患病的出现是医学科学的一个关键挑战。新的人畜共患病以看似随机的方式定期从野生动物中出现，来自地球仪的不同地区，来自广泛多样的野生动物物种。我们理解是什么驱动了这一过程的能力受到了以下因素的阻碍：缺乏对导致出现的过程的严格分析;我们缺乏对野生动物中微生物多样性（“人畜共患病池”）的了解，而新的人畜共患病经常从野生动物中出现;以及我们对致病因素的理解不足，这些致病因素解释了为什么一些病毒能够跨越物种障碍，而另一些则不能。在这个应用程序中，我们汇集了新兴疾病生态学家和建模师，病毒生物信息学家和分子病毒学家的多学科团队，他们是各自领域的领导者，并且已经合作研究人畜共患病的出现。基于初步数据表明蝙蝠是一个关键的野生动物库，而这种出现是由于一系列人为驱动因素，该团队将1）为未来蝙蝠病毒的出现开发全球“热点”预测模型; 2）利用大量蝙蝠生物样本储存库，在这些“热点”进行有针对性的监测，寻找已知和未发现的蝙蝠病原体，阐明蝙蝠“病毒组”的未知多样性; 3）使用一系列体外技术（包括在蝙蝠细胞培养中感染），研究这些新病毒的发病机制，以及尚未在人类中出现的现有蝙蝠病毒库。这种多学科方法代表了第一次协同努力，以了解与最近出现的SARS、尼帕、亨德拉、埃博拉和马尔堡病毒相关的一组关键野生动物宿主内出现过程的深度和广度。新出现的人畜共患病（如艾滋病毒/艾滋病、流感）是对全球健康的主要威胁，每年在美国和国外造成数万人死亡，其中一些是最近从蝙蝠身上出现的（SARS、埃博拉病毒、尼帕病毒）。这项研究提供了一种方法来预测下一个新出现的蝙蝠人兽共患病最有可能出现的地区，并提出了对这些地区的有针对性的监测。 在这些地区使用最先进的分子技术的动物。它将描述新病毒的特征，并研究这些病毒的发病机制，以及一个尚未在人群中出现的已知蝙蝠病毒库：因此，这是一种预测性的，积极主动的方法来对抗最引人注目的新兴病原体。

DESCRIPTION (provided by investigator): Emerging zoonoses are a significant threat to global public health and our economies. The majority are caused by pathogens that emerge with increasing frequency from wildlife hosts (e.g. HIV-1 from chimpanzees, SARS CoV from bats and civets, Nipah virus from fruit bats). This group of diseases alone causes tens of thousands of deaths each year, and some outbreaks (e.g. SARS) have cost the global economy tens of billions of dollars. However, despite the huge social, demographic and economic impact of EIDs, there has been little advance in our understanding of the underlying process of how these wildlife zoonoses emerge, and in developing predictive approaches to prevent future emergence. Developing predictive and proactive approaches to zoonotic emergence is a key challenge to medical science. New zoonoses emerge regularly from wildlife in a seemingly random way, from disparate regions of the globe, and from a wide diversity of wildlife species. Our ability to understand what drives this process is hampered by a lack of rigorous analyses of the processes that cause emergence; our lack of knowledge of the diversity of microbes in wildlife (the `zoonotic pool') from which new zoonoses regularly emerge; and our poor understanding of pathogenic factors that explain why some viruses are able to cross the species barrier while others are not. In this application, we bring together a multidisciplinary team of emerging disease ecologists and modelers, viral bioinformaticists, and molecular virologists who are leaders in their fields, and who have already collaborated together to study zoonotic disease emergence. Building on preliminary data that demonstrates bats are a key wildlife reservoir, and that emergence is due to a range of anthropogenic drivers, this team will 1) develop predictive models of global `hotspots' for the future emergence of bat viruses; 2) use a large repository of bat biological samples to conduct targeted surveillance in these `hotspots' for known and undiscovered bat pathogens, elucidating the unknown diversity of the bat `virome' and; 3) using a range of in vitro techniques (including infection in bat cell culture), examine the pathogenesis of these new viruses, and a pool of available bat viruses which have not yet emerged in humans. This multidisciplinary approach represents the first, concerted effort to understand the depth and breadth of the process of emergence within a key group of wildlife hosts associated with the recent emergence of SARS, Nipah, Hendra, Ebola and Marburg viruses. PUBLIC HEALTH RELEVANCE Emerging zoonoses (e.g. HIV/AIDS, Influenza) are a major threat to health globally, causing tens of thousands of deaths each year in the USA and abroad and a number of these have emerged from bats recently (SARS, Ebola, Nipah). This research provides a way to predict the regions where the next new emerging zoonoses from bats is most likely to emerge, and proposes targeted surveillance of these animals using state-of-the- art molecular techniques in those regions. It will characterize new viruses, and study the pathogenesis of these, and a bank of known bat viruses that have not yet emerged in the human population: It is therefore a predictive, proactive approach to combating the most high profile group of emerging pathogens.