Biological and Human Dimensions of Primate Retroviral Transmission

疾病生态学中最持久的谜团之一是艾滋病大流行的时间。艾滋病在20世纪70年代末作为一个临床实体出现，但导致艾滋病大流行的逆转录病毒HIV-1在几十年前从野生灵长类动物进入人类群体，可能是在20世纪之交。在这段漫长的时间里，艾滋病毒在哪里？我们为艾滋病的延迟出现提出了一个新的生态学模型。从概念上讲，在由多个松散相连的亚种群组成的集合种群中，通过亚种群之间的局部传播、局部灭绝和远距离迁移之间的动态平衡，病原体可以在低水平上无限期地持续存在。这种情况可能准确地描述了一个村庄网络，其中人口规模小，迁移率低，一个多世纪前撒哈拉以南非洲的情况就是这样。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。2009年，我们在乌干达Kibale国家公园进行了20多年的研究，记录了三种猿类逆转录病毒在野生红瘤猴集合种群中共同传播的情况。我们将在一个核心的社会群体中收集关于社会互动、人口统计学、健康和动物感染的详细数据。我们还将研究一系列20个红色根瘤菌亚群，每个亚群居住在一个单独的、孤立的森林碎片中。我们将使用追溯到1955年的森林覆盖遥感图像的时间序列，以及使用高变量核DNA标记的种群遗传分析来确定这些亚种群的历史连接性。我们将评估每种动物随着时间的推移的感染状态，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，但它们不足以解释为什么逆转录病毒可能会出现。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水库传播和传播的条件。因此，我们将对这一系统中人-灵长类接触和人畜共患传播的根本生态社会驱动因素进行综合分析。我们将研究社会网络，以了解社会资源是如何构成与人与灵长类接触和人畜共患传播风险相关的关键活动的，我们将在广泛的人口样本中探索人与灵长类接触和疾病传播的知识、信念和看法。我们将通过关联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来协调感知风险和实际风险。我们研究的最终成果将是一套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存在，以及关于人类社会因素如何导致撒哈拉以南非洲相关人口的人畜共患感染风险的关联分析。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如何从“阴燃”的亚临床感染发展为全面的大流行。

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.