Sylvatic Reservoirs of Human Monkeypox

描述（由申请人提供）：本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的挑战。该项目将3个不同的组成部分联系起来：实验室研究，以表征感染啮齿类动物的感染过程和病毒血症，自然啮齿类动物种群病毒感染的实地研究，以及大范围的时空生态地理分析，以提供空间，范围广泛的系统视图。结果将是对MPX病毒可能宿主的综合看法，并在了解病毒的自然传播方面取得重大进展。研究团队包括3个学术机构和美国及外国政府机构，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，通过直接从MPX现场获得的哺乳动物的潜在宿主物种的实验室挑战研究，通过结合对非洲哺乳动物MPX感染的密集实地调查，以及通过探索新的贝叶斯建模方法来了解整个非洲动物和人类MPX病例发生的时空分布。所产生的数据将利用我们团队开发的重组（荧光素酶+）猴痘构建体的新的体内成像技术，表征每种哺乳动物MPX的感染进展和发病机制；在与近期人类MPX病例相关的地点，野生啮齿动物中MPX感染的当地流行情况；时空分析扩大了整个大陆的范围，在定量的环境背景下，将病毒的分布与宿主哺乳动物的分布进行比较。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）的每一种病毒的感染特征，并将通过测量病毒血症长度、组织趋向性和各种病毒-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.