Sylvatic Reservoirs of Human Monkeypox

描述(由申请人提供)：这项研究的重点是阐明猴痘(MPX)病毒的生态和自然历史的未知方面的挑战。该项目将3个不同的部分联系在一起：实验室研究以确定受感染啮齿动物的感染和病毒血症的过程，实地研究自然啮齿动物群体中的病毒感染，以及广泛的空间和时间生态-地理分析，以提供系统的空间和范围广泛的视角。其结果将是对MPX病毒可能的宿主的综合看法，并在理解病毒的自然传播方面取得重大进展。研究团队包括3个学术机构和美国和外国政府机构，并利用新技术在现场和实验室环境中探索MPX。该项目是对迄今的其他研究的补充，它以直接从MPX现场获得的哺乳动物为基础对潜在的宿主物种进行实验室挑战研究，纳入对MPX感染的非洲哺乳动物的密集实地调查，并探索新的贝叶斯建模方法，以了解MPX病例在整个非洲动物和人类中的空间和时间分布。生成的数据将使用我们团队开发的重组(荧光素酶+)猴痘构建体的新体内成像来表征MPX在每个哺乳动物物种中的感染进展和发病机制；与最近的人类MPX病例相关的地点野生啮齿动物中MPX感染的局部流行；以及在大陆扩大范围并将病毒分布与宿主它们的哺乳动物物种在量化环境背景下的病毒分布进行比较的时空分析。这项研究将在实验室挑战研究中比较和对比来自两个MPX分支(西非和中非)的病毒的感染特征，并将通过测量病毒血症的长度、组织趋向性和不同病毒-啮齿动物配对的病毒脱落模式来评估一组哺乳动物物种的宿主潜力。

DESCRIPTION (provided by applicant): This research focuses on the challenge of illuminating unknown aspects of the ecology and natural history of Monkeypox (MPX) viruses. The project links 3 disparate components: lab studies to characterize the course of infection and viremia in infected rodents, field studies of viral infections in natural rodent populations, and broad-scale spatial and temporal ecological-geographic analyses to provide a spatial, range-wide view of the system. The result will be a synthetic view of likely reservoir hosts of MPX viruses, and significant advances in the understanding of the natural transmission of the virus. The research team includes 3 academic institutions and US and foreign government agencies, and take advantage of novel technologies to explore MPX in both field and lab settings. This project complements other studies to date by basing laboratory challenge studies of potential reservoir host species on mammals obtained directly from MPX field sites, by incorporating intensive field surveys of African mammals for MPX infections, and by exploring novel Bayesian modeling approaches to understanding the distribution of MPX case-occurrences in animals and humans throughout Africa in both space and time. Data generated will characterize infection progression and pathogenesis of MPX in each mammal species using new in vivo imaging with recombinant (luciferase+) Monkeypox constructs developed by our team; local prevalence of MPX infections in wild rodents at sites associated with recent human MPX cases; and spatiotemporal analyses that broaden the scope continentally, and that compare virus distributions with those of the mammal species that host them in a quantitative environmental context. The study will compare and contrast the infection characteristics of viruses from each of the two MPX clades (Western and Central African) in laboratory challenge studies, and will assess reservoir host potential of a set of mammal species by measuring length of viremia, tissue tropisms, and modes of viral shedding for various virus-rodent pairings.