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，以表征感染啮齿动物的感染和病毒血症过程，自然啮齿动物种群中病毒感染的实地研究，以及大规模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MPX病毒可能的储存宿主的综合观点，以及对该病毒自然传播的理解的重大进展。该研究团队包括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。该项目补充了其他研究的基础上，实验室挑战研究的潜在水库宿主物种的哺乳动物直接从MPX现场，通过将密集的实地调查非洲哺乳动物的MPX感染，并通过探索新的贝叶斯建模方法，了解分布MPX病例发生在整个非洲的动物和人类在空间和时间。所产生的数据将使用重组的新的体内成像来表征MPX在每个哺乳动物物种中的感染进展和发病机制。（荧光素酶+）猴痘构建体由我们的团队开发;在与最近的人类MPX病例相关的地点，野生啮齿动物中MPX感染的局部流行;和时空分析，扩展了大陆的范围，并在定量环境背景下比较病毒分布与宿主哺乳动物的分布。本研究将在实验室攻毒研究中比较和对比两个MPX进化枝（西非和中非）的病毒感染特征，并通过测量各种病毒-啮齿动物配对的病毒血症长度、组织嗜性和病毒脱落模式，评估一组哺乳动物种属的储库宿主潜力。

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.