Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA, United Kingdom.
J Virol. 2010 Apr;84(8):3974-83. doi: 10.1128/JVI.02078-09. Epub 2010 Feb 3.
A key question in pandemic influenza is the relative roles of innate immunity and target cell depletion in limiting primary infection and modulating pathology. Here, we model these interactions using detailed data from equine influenza virus infection, combining viral and immune (type I interferon) kinetics with estimates of cell depletion. The resulting dynamics indicate a powerful role for innate immunity in controlling the rapid peak in virus shedding. As a corollary, cells are much less depleted than suggested by a model of human influenza based only on virus-shedding data. We then explore how differences in the influence of viral proteins on interferon kinetics can account for the observed spectrum of virus shedding, immune response, and influenza pathology. In particular, induction of high levels of interferon ("cytokine storms"), coupled with evasion of its effects, could lead to severe pathology, as hypothesized for some fatal cases of influenza.
在大流行性流感中，一个关键问题是先天免疫和靶细胞耗竭在限制初次感染和调节病理学方面的相对作用。在这里，我们使用马流感病毒感染的详细数据来模拟这些相互作用，将病毒和免疫（I 型干扰素）动力学与细胞耗竭的估计值结合起来。所得动力学表明先天免疫在控制病毒脱落的快速峰值方面起着强大的作用。作为推论，与仅基于病毒脱落数据的基于人类流感的模型相比，细胞的耗竭程度要低得多。然后，我们探讨了病毒蛋白对干扰素动力学的影响差异如何解释观察到的病毒脱落、免疫反应和流感病理学谱。特别是，高水平干扰素的诱导（“细胞因子风暴”），加上对其作用的逃避，可能导致严重的病理，正如一些致命的流感病例所假设的那样。
