Model of influenza A virus infection: dynamics of viral antagonism and innate immune response.

Model of influenza A virus infection: dynamics of viral antagonism and innate immune response.
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DOI:
10.1016/j.jtbi.2014.02.029
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发表时间:
2014-06-21
影响因子:
2
通讯作者:
Hayot, F.
Hayot, F.
中科院分区:
生物学4区
文献类型:
--
作者:
Fribourg, M.;Hartmann, B.;Schmolke, M.;Marjanovic, N.;Albrecht, R. A.;Garcia-Sastre, A.;Sealfon, Sc;Jayaprakash, C.;Hayot, F.

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病毒对宿主反应的拮抗作用是病毒致病性的重要组成部分。免疫应答和病毒拮抗作用之间的相互作用的研究是具有挑战性的,因为涉及在多个时间尺度上起作用的许多过程。在这里,我们开发了一个常微分方程模型,以调查早期,实验测量,人类单核细胞来源的树突状细胞感染两种H1N1流感病毒的不同临床结果的反应:大流行A/加州/4/2009和季节性A/新喀里多尼亚/20/1999。我们的研究结果揭示了病毒拮抗作用的强度,以及它阻碍先天免疫反应的时间尺度,在两种病毒之间存在显着差异,这一点可以通过它们对一些测量基因的时间行为的影响来明确。因此,该模型揭示了对不同H1N1病毒的先天免疫反应的可变性的机制。
Viral antagonism of host responses is an essential component of virus pathogenicity. The study of the interplay between immune response and viral antagonism is challenging due to the involvement of many processes acting at multiple time scales. Here we develop an ordinary differential equation model to investigate the early, experimentally-measured, responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcome: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999. Our results reveal how the strength of virus antagonism, and the time scale over which it acts to thwart the innate immune response, differ significantly between the two viruses, as is made clear by their impact on the temporal behavior of a number of measured genes. The model thus sheds light on the mechanisms that underlie the variability of innate immune responses to different H1N1 viruses.
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