PDF(Pubmed)
Abstract：
The dynamic nature of the SIV population during disease progression in the SIV/macaque model of AIDS and the factors responsible for its behavior have not been documented, largely owing to the lack of sufficient spatial and temporal sampling of both viral and host data from SIV-infected animals. In this study, we detail Bayesian coalescent inference of the changing collective intra-host viral effective population size (Ne ) from various tissues over the course of infection and its relationship with what we demonstrate is a continuously changing immune cell repertoire within the blood. Although the relative contribution of these factors varied among hosts and time points, the adaptive immune response best explained the overall periodic dynamic behavior of the effective virus population. Data exposing the nature of the relationship between the virus and immune cell populations revealed the plausibility of an eco-evolutionary mathematical model, which was able to mimic the large-scale oscillations in Ne through virus escape from relatively few, early immunodominant responses, followed by slower escape from several subdominant and weakened immune populations. The results of this study suggest that SIV diversity within the untreated host is governed by a predator-prey relationship, wherein differing phases of infection are the result of adaptation in response to varying immune responses. Previous investigations into viral population dynamics using sequence data have focused on single estimates of the effective viral population size (Ne ) or point estimates over sparse sampling data to provide insight into the precise impact of immune selection on virus adaptive behavior. Herein, we describe the use of the coalescent phylogenetic frame- work to estimate the relative changes in Ne over time in order to quantify the relationship with empirical data on the dynamic immune composition of the host. This relationship has allowed us to expand on earlier simulations to build a predator-prey model that explains the deterministic behavior of the virus over the course of disease progression. We show that sequential viral adaptation can occur in response to phases of varying immune pressure, providing a broader picture of the viral response throughout the entire course of progression to AIDS.
摘要：
在艾滋病的SIV/猕猴模型中，SIV群体在疾病进展期间的动态性质以及导致其行为的因素尚未被记录，主要是由于缺乏足够的空间和时间采样的病毒和宿主数据从SIV感染的动物。在这项研究中,我们详细介绍了贝叶斯合并推断,即在感染过程中,来自各种组织的总体宿主内病毒有效种群大小(Ne)的变化及其与我们所证明的血液中免疫细胞库不断变化的关系.尽管这些因素的相对贡献在宿主和时间点之间有所不同，适应性免疫反应最好地解释了有效病毒群体的整体周期性动态行为。揭示病毒和免疫细胞群体之间关系性质的数据揭示了生态进化数学模型的合理性，它能够通过相对较少的病毒逃逸来模拟Ne的大规模振荡，早期免疫显性反应，其次是缓慢逃离几个优势和减弱的免疫群体。这项研究的结果表明，未经处理的宿主内的SIV多样性受捕食者-猎物关系的支配，其中感染的不同阶段是对不同免疫应答的适应的结果。以前使用序列数据对病毒种群动态的研究集中在有效病毒种群大小（Ne）的单个估计或稀疏采样数据的点估计上，以深入了解免疫选择对病毒适应性行为的精确影响。在这里，我们描述了使用合并系统发育框架来估计Ne随时间的相对变化，以便量化与宿主动态免疫组成的经验数据的关系。这种关系使我们能够扩展早期的模拟，以建立一个捕食者-猎物模型，该模型解释了病毒在疾病进展过程中的确定性行为。我们表明，连续的病毒适应可以发生在不同的免疫压力阶段的反应，提供了在整个艾滋病发展过程中病毒反应的更广泛的图片。
