Understanding the impact of pathogen exposure on the within-host dynamics and its outcome in terms of infectiousness is a key issue to better understand and control the infection spread. Most experimental and modelling studies tackling this issue looked at the impact of the exposure dose on the infection probability and pathogen load, very few on the within-host immune response. Our aim was to explore the impact on the within-host response not only of the exposure dose, but also of its duration and peak, for contrasted virulence levels. We used an integrative modelling approach of the within-host dynamics at the between-cell level. We focused on the porcine reproductive and respiratory syndrome virus, a major concern for the swine industry. We quantified the impact of exposure and virulence on the viral dynamics and immune response by global sensitivity analyses and descriptive statistics. We found that the area under the viral curve, an indicator of the infection severity, was fully determined by the exposure intensity. The infection duration increased with the strain virulence and, for a given strain, exhibited a positive linear correlation with the exposure intensity logarithm and the exposure duration. Taking into account the exposure intensity is hence necessary. Besides, representing the exposure due to contacts by a single punctual dose would tend to underestimate the infection duration. As the infection severity and duration both contribute to the pig infectiousness, a prolonged exposure of the adequate intensity would be recommended in an immuno-epidemiological context.

中文翻译：

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为什么要在宿主范围内考虑暴露，何时以及如何暴露？对PRRSv感染的建模贡献。

从传染性的角度了解病原体暴露对宿主内部动态及其后果的影响是更好地了解和控制感染传播的关键问题。解决这个问题的大多数实验和模型研究都研究了暴露剂量对感染概率和病原体负荷的影响，而对宿主内部免疫反应的影响很小。我们的目的是探讨毒力水平不同时，不仅暴露剂量，而且其持续时间和峰值对宿主内部反应的影响。我们使用了单元间级别的主机内部动态的集成建模方法。我们专注于猪繁殖和呼吸综合症病毒，这是养猪业的主要问题。通过全球敏感性分析和描述性统计，我们量化了暴露和毒力对病毒动力学和免疫反应的影响。我们发现病毒曲线下的面积（感染严重程度的指标）完全由暴露强度决定。感染持续时间随菌株毒力的增加而增加，对于给定的菌株，其暴露强度与对数强度和暴露时间呈线性正相关。因此有必要考虑曝光强度。此外，用单点剂量来表示由于接触引起的接触可能会低估感染持续时间。由于感染的严重程度和持续时间均会影响猪的传染性，因此在免疫流行病学背景下，建议长时间暴露于足够的强度。