Dynamics of Influenza Virus Infection and Pathology
Dynamics of Influenza Virus Infection and Pathology
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DOI：
10.1128/jvi.02078-09
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发表时间：
2010-04-01
影响因子：
5.4
通讯作者：
Gog, Julia R.
中科院分区：
文献类型：
--
作者：
Saenz, Roberto A.;Quinlivan, Michelle;Gog, Julia R.
大流行性流感的一个关键问题是先天免疫和靶细胞耗竭在限制原发感染和调节病理中的相对作用。在这里，我们使用马流感病毒感染的详细数据，结合病毒和免疫（I型干扰素）动力学与细胞耗竭的估计，这些相互作用的模型。由此产生的动力学表明，先天免疫在控制病毒脱落的快速峰值方面发挥着强大的作用。作为一个推论，细胞的消耗比仅基于病毒脱落数据的人类流感模型所显示的要少得多。然后，我们探索病毒蛋白对干扰素动力学影响的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，诱导高水平的干扰素（“细胞因子风暴”），加上逃避其影响，可能会导致严重的病理，如一些致命的流感病例的假设。
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.