Abstract：
AbstractInfectious disease dynamics operate across biological scales: pathogens replicate within hosts but transmit among populations. Functional changes in the pathogen-host interaction thus generate cascading effects across organizational scales. We investigated within-host dynamics and among-host transmission of three strains (SAT-1, -2, -3) of foot-and-mouth disease viruses (FMDVs) in their wildlife host, African buffalo. We combined data on viral dynamics and host immune responses with mathematical models to ask the following questions: How do viral and immune dynamics vary among strains? Which viral and immune parameters determine viral fitness within hosts? And how do within-host dynamics relate to virus transmission? Our data reveal contrasting within-host dynamics among viral strains, with SAT-2 eliciting more rapid and effective immune responses than SAT-1 and SAT-3. Within-host viral fitness was overwhelmingly determined by variation among hosts in immune response activation rates but not by variation among individual hosts in viral growth rate. Our analyses investigating across-scale linkages indicate that viral replication rate in the host correlates with transmission rates among buffalo and that adaptive immune activation rate determines the infectious period. These parameters define the virus\'s relative basic reproductive number (ℛ0), suggesting that viral invasion potential may be predictable from within-host dynamics.
摘要：
传染病动力学在生物尺度上运作：病原体在宿主内复制，但在人群中传播。因此，病原体-宿主相互作用的功能变化会产生跨组织规模的级联效应。我们调查了三种口蹄疫病毒（FMDV）菌株（SAT-1，-2，-3）在其野生动物宿主中的宿主内动态和宿主间传播，非洲水牛.我们将病毒动力学和宿主免疫反应的数据与数学模型相结合，提出以下问题：病毒和免疫动力学在毒株之间如何变化？哪些病毒和免疫参数决定了宿主内的病毒适合性？宿主内动力学与病毒传播有何关系？我们的数据揭示了病毒株之间宿主内动力学的对比，与SAT-1和SAT-3相比，SAT-2引起更快速和有效的免疫反应。宿主内病毒适合度主要由免疫应答激活率的宿主之间的差异决定，而不是由病毒生长速率的个体宿主之间的差异决定。我们调查跨尺度联系的分析表明，宿主中的病毒复制率与水牛之间的传播率相关，适应性免疫激活率决定了感染期。这些参数定义病毒的相对基本繁殖数（0），这表明病毒入侵潜力可以从宿主内动力学预测。
