Stress hormone effects on disease resistance, tolerance and transmission
Stress hormone effects on disease resistance, tolerance and transmission
批准号:
1257773
负责人:
Lynn Martin
金额:
$60.41万
依托单位国家:
美国
项目类别:
Continuing Grant
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-08-15 至 2019-07-31
中文摘要
超级传播者对其他宿主的感染负有不成比例的责任。也许最著名的人类超级传播者是伤寒玛丽,她因沙门氏菌传播导致53人死亡。虽然“伤寒玛丽”的频率尚不清楚,但它们可能并不罕见。超级传播与SARS(突发性急性呼吸系统综合症)和艾滋病毒在全球的迅速蔓延有关。对于大多数传染病,20%的宿主引起80%的感染。本研究的目的是确定糖皮质激素,一种与疾病传播有关的主要脊椎动物应激激素,是否参与了超传播。应激激素可以通过影响寄生虫(或媒介,如蚊子和咬人的苍蝇)如何选择捕食的宿主,宿主如何抵抗或耐受寄生虫,或者宿主如何将寄生虫传播给其他宿主或媒介来影响超级传播。令人惊讶的是,从来没有一个系统的研究应激激素对一个复杂的宿主-媒介-寄生虫系统的所有方面的影响。由于许多人为和自然因素改变了应激激素的调节,这些因素在全球变化的背景下越来越重要,因此这一知识差距是重要的,值得关注。通过了解应激激素如何以及何时影响宿主-寄生虫相互作用,我们可能能够更好地预测和控制人畜共患疾病的爆发。智力优势:为了研究应激激素在超传播中的作用,将研究斑马雀(ZEFI)、库蚊和西尼罗河病毒(WNV)之间的相互作用。之所以选择西尼罗河病毒,是因为它已经导致一些鸣禽种群大量死亡,并被认为是造成3.3万多人感染和1150人死亡的原因。之所以选择ZEFI和库蚊,是因为它们的基因组已经测序,为强有力的实验方法提供了机会。预计应激激素会影响i) ZEFI对库蚊暴露的行为,ii)库蚊对ZEFI的吸血偏好,iii) ZEFI对西尼罗河病毒感染的抗性,iv) ZEFI对西尼罗河病毒感染的耐受性,和/或v) ZEFI向库蚊传播西尼罗河病毒的能力。最终,这些数据将用于直接确定应激激素何时产生最大影响,这些信息对人类和野生动物种群都有价值。更广泛的影响:在动物中,超级传播似乎对几种人畜共患疾病(从动物向人群传播的感染)的传播很重要,例如西尼罗河病毒和一些汉坦病毒。在全球变化的背景下,了解超传播的基础研究具有重要的社会价值,因为预计人畜共患疾病将变得更加普遍。与每年吸引100多万游客的坦帕科学与工业博物馆(Tampa Museum of Science and Industry)的合作将包括开发一个科学工作剧院(Science Works Theater),帮助公众了解疾病生态学。还将为希尔斯堡县高中教师举办培训讲习班,为教师提供工具,培训现代疾病生物学方面的初级科学家。对于大约40%来自弱势群体背景的南加州大学学生,将提供丰富的学习经验。参与该项目的个人将学习畜牧业、小手术、如何在高度安全的传染病研究机构工作、现代实验室分析、数据分析和科学写作。
英文摘要
Superspreaders are disproportionately responsible for the infections of other hosts. Perhaps the best-known human superspreader was Typhoid Mary, who caused 53 deaths due to Salmonella bacteria transmission. Although the frequency of "Typhoid Marys" is unclear, they are probably not rare. Superspreading is implicated in the rapid expansion of SARS (Sudden Acute Respiratory Syndrome) and HIV across the globe. For most infectious diseases, 20% of hosts cause 80% of infections. The goal of this research is to determine whether glucocorticoids, major vertebrate stress hormones that have been implicated in disease transmission, are involved in superspreading. Stress hormones could impact superspreading by affecting how parasites (or vectors, such as mosquitos and biting flies) choose hosts on which to feed, how hosts resist or tolerate parasites, or how hosts transmit parasites to other hosts or vectors. Surprisingly, there has never been a systematic study of the effects of stress hormones on all aspects of one complex host-vector-parasite system. This knowledge gap is significant and deserves attention because many anthropogenic and natural factors alter stress hormone regulation, and these factors are increasingly important in the context of global change. By knowing how and when stress hormones affect host-parasite interactions, we may become better able to predict and control zoonotic disease outbreaks. Intellectual merit: To investigate the role of stress hormones in superspreading, interactions among zebra finches (ZEFI), Culex pipiens mosquitos, and West Nile virus (WNV) will be studied. WNV was chosen because it has decimated some songbird populations and is thought responsible for more than 33,000 human infections and 1150 deaths. ZEFI and Culex were chosen because their genomes have been sequenced, providing opportunities for strong experimental approaches. Stress hormones are predicted to impact i) ZEFI behavior to Culex exposure, ii) Culex blood-feeding preference on ZEFI, iii) ZEFI resistance to WNV infection, iv) ZEFI tolerance of WNV infection, and/or v) ZEFI competency to transmit WNV to Culex. Ultimately, data will be used to determine directly when stress hormones have the largest impacts, information valuable for human and wildlife populations.Broader impacts: In animals, superspreading appears important for the transmission of several zoonotic diseases (infections that spill from animal into human populations) such as West Nile virus and some hantaviruses. In the context of global change, basic research on understanding superspreading has significant societal value because zoonotic diseases are predicted to become more prevalent. Collaboration with the Tampa Museum of Science and Industry, which attracts more than one million guests annually, will include the development of a Science Works Theater that helps the public understand disease ecology. Training workshops for Hillsborough County high school teachers will also be held, providing teachers tools to train incipient scientists in modern disease biology. For USF students, about 40% of whom come from under-represented backgrounds, robust learning experiences will be provided. Individuals on the project will learn animal husbandry, minor surgeries, how to work in a high-security infectious disease research facility, modern lab assays, data analysis, and scientific writing.
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