Biological and Human Dimensions of Primate Retroviral Transmission

灵长类逆转录病毒传播的生物学和人类维度

• 批准号: 8719002
• 负责人: Tony L. Goldberg
• 金额: $ 48.13万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8719002
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Affect; Africa South of the Sahara; African; American; Animals; Back; Behavior; Belief; Biological; British; Clinical; Colobus Genus; DNA Markers; Data; Demography; Diagnostic tests; Dimensions; Disease; Ecology; Equilibrium; Extinction (Psychology); Future; Goals; HIV; HIV-1; Health; Health Surveys; Human; Image; Individual; Infection; Infectious Diseases Research; Instruction; Interview; Knowledge; Light; Link; Maps; Modeling; Molecular; Monkeys; Nuclear; Pathway interactions; Perception; Plant Roots; Population; Population Genetics; Population Sizes; Primate Retrovirus; Primates; Procolobus; Relative (related person); Research; Research Infrastructure; Resources; Retroviridae; Risk; Sampling; Scientist; Series; Simian Retroviruses; Social Interaction; Social Network; Staging; Structure; Students; System; Testing; Time; Training; Uganda; Viral; Zoonoses; Zoonotic Infection; base; behavioral health; disease transmission; forest; genetic analysis; migration; nonhuman primate; novel; pandemic disease; pathogen; prevent; social; social capital; social group; time use; transmission process

One of the great enduring mysteries in disease ecology is the timing of the AIDS pandemic. AIDS emerged as a clinical entity in the late 1970s, but HIV-1, the retrovirus that causes pandemic AIDS, entered the human population from wild primates many decades earlier, probably near the turn of the 20th century. Where was HIV during this long interval? We propose a novel ecological model for the delayed emergence of AIDS. Conceptually, in a metapopulation consisting of multiple, loosely interconnected sub-populations, a pathogen could persist at low levels indefinitely through a dynamic balance between localized transmission, localized extinction, and long-distance migration between sub-populations. This situation might accurately describe a network of villages in which population sizes are small and rates of migration are low, as would have been the case in Sub-Saharan Africa over a century ago. We will test our model in a highly relevant non-human primate system. In 2009, we documented three simian retroviruses co-circulating in a metapopulation of wild red colobus monkeys (Procolobus rufomitratus) in Kibale National Park, Uganda, where we have conducted research for over two decades. We will collect detailed data on social interactions, demography, health, and infection from animals in a core social group. We will also study a series of 20 red colobus sub-populations, each inhabiting a separate, isolated forest fragment. We will determine the historic connectivity of these sub-populations using a time series of remotely sensed images of forest cover going back to 1955, as well as using population genetic analyses of hypervariable nuclear DNA markers. We will assess the infection status of each animal over time and use viral molecular data to reconstruct transmission pathways. Our transmission models will define the necessary conditions for a retrovirus to persist, but they will not be sufficient to explain why a retrovirus might emerge. This is because human social factors ultimately create the conditions that allow zoonotic diseases to be transmitted from animal reservoirs and to spread. We will therefore conduct an integrated analysis of the root eco-social drivers of human-primate contact and zoonotic transmission in this system. We will study social networks to understand how social resources structure key activities relevant to human-primate contact and zoonotic transmission risk, and we will explore knowledge, beliefs, and perceptions of human-primate contact and disease transmission for a broad sample of the population. We will reconcile perceived risk with actual risk through a linked human health survey and diagnostic testing for zoonotic primate retroviruses. The ultimate product of our research will a data-driven set of transmission models to explain the long-term persistence of retroviruses within a metapopulation of hosts, as well as a linked analysis of how human social factors contribute to zoonotic infection risk in a relevant Sub-Saharan African population. Our study will elucidate not only the origins of HIV/AIDS, but also how early-stage zoonoses in general progress from "smoldering" subclinical infections to full-fledged pandemics.

疾病生态学中最大的一个持久的谜团是艾滋病流行的时间。艾滋病在20世纪70年代末作为一种临床实体出现，但导致艾滋病大流行的逆转录病毒HIV-1早在几十年前就从野生灵长类动物进入了人类群体，可能是在世纪之交。在这段漫长的时间里，艾滋病毒在哪里？我们提出了一个新的生态模型的延迟出现的艾滋病。从概念上讲，在由多个松散相互联系的亚群组成的集合种群中，病原体可以通过局部传播、局部灭绝和亚群之间的长距离迁移之间的动态平衡而无限期地保持在低水平。这种情况可能准确地描述了一个人口规模小、移民率低的村庄网络，就像世纪前撒哈拉以南非洲的情况一样。我们将在一个高度相关的非人类灵长类动物系统中测试我们的模型。在2009年，我们记录了三种猿类逆转录病毒在乌干达基巴莱国家公园的野生红疣猴（Procolobus rufomitratus）的集合种群中共同传播，我们在那里进行了二十多年的研究。我们将收集有关社会互动，人口统计学，健康和感染的动物在一个核心社会群体的详细数据。我们还将研究一系列的20个红疣猴亚种群，每个亚种群居住在一个单独的，孤立的森林片段。我们将使用可追溯到1955年的森林覆盖遥感图像时间序列以及高变核DNA标记的种群遗传分析来确定这些亚种群的历史连通性。我们将评估每只动物随时间的感染状况，并使用病毒分子数据重建传播途径。我们的传播模型将定义逆转录病毒持续存在的必要条件，但它们不足以解释逆转录病毒为什么会出现。这是因为人类社会因素最终创造了允许人畜共患病从动物宿主传播和传播的条件。因此，我们将对该系统中人与灵长类动物接触和人畜共患病传播的根本生态社会驱动因素进行综合分析。我们将研究社交网络，以了解社会资源如何构建与人-灵长类动物接触和人畜共患病传播风险相关的关键活动，我们将探索知识，信念和人-灵长类动物接触和疾病传播的广泛人群样本的看法。我们将通过一项相关的人类健康调查和人畜共患灵长类逆转录病毒的诊断测试，使感知风险与实际风险相一致。我们研究的最终产品将是一组数据驱动的传播模型，以解释逆转录病毒在宿主集合种群中的长期持续性，以及人类社会因素如何导致相关撒哈拉以南非洲人口中人畜共患病感染风险的相关分析。我们的研究不仅将阐明艾滋病毒/艾滋病的起源，而且还将阐明早期人畜共患病一般是如何从“阴燃”亚临床感染发展到全面流行的。