Sylvatic Reservoirs of Human Monkeypox

这项研究的重点是阐明猴痘（MPX）病毒生态学和自然史的未知方面。该项目将 3 个不同的组成部分联系起来：实验室研究，以描述受感染啮齿动物的感染和病毒血症过程；对自然啮齿动物种群中病毒感染的现场研究；以及大范围的时空生态地理分析，以提供系统的空间、范围视图。其结果将是对 MPX 病毒可能的储存宿主的综合看法，并在了解病毒自然传播方面取得重大进展。该研究团队包括3个学术机构以及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。该项目补充了迄今为止的其他研究，通过对直接从 MPX 现场获得的哺乳动物进行潜在储存宿主物种的实验室挑战研究，结合对非洲哺乳动物 MPX 感染的深入实地调查，并通过探索新颖的贝叶斯建模方法来了解 MPX 病例在整个非洲动物和人类中的空间和时间分布。生成的数据将表征感染 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技术，研究每个哺乳动物物种中 MPX 的进展和发病机制；在与近期人类 MPX 病例相关的地点，野啮齿动物中 MPX 感染的当地流行情况；以及扩大大陆范围的时空分析，并将病毒分布与宿主它们的哺乳动物物种的分布进行比较 定量的环境背景。该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、组织向性和各种病毒与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储存宿主潜力。

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, rangewide 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 wildrodents 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.