Kinetics of coinfection with influenza A virus and Streptococcus pneumoniae.
Kinetics of coinfection with influenza A virus and Streptococcus pneumoniae.
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甲型流感病毒与肺炎链球菌合并感染的动力学。
DOI：
10.1371/journal.ppat.1003238
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发表时间：
2013-03
期刊：
影响因子：
6.7
通讯作者：
Perelson AS
中科院分区：
文献类型：
--
作者：
Smith AM;Adler FR;Ribeiro RM;Gutenkunst RN;McAuley JL;McCullers JA;Perelson AS
继发性细菌感染是流行性流感和大流行性流感期间疾病和死亡的主要原因。实验研究表明流感和某些细菌（特别是肺炎链球菌）之间存在致命的协同作用，但所涉及的确切过程尚不清楚。为了阐明机制并确定病原体剂量和菌株对疾病的影响，我们用 H1N1 亚型甲型流感病毒 A/Puerto Rico/8/34 (PR8) 或表达 1918 PB1-F2 蛋白的版本 (PR8-PB1-F2(1918)) 感染小鼠组，然后 7 天后用两种肺炎链球菌菌株（2 型 D39 或 3 型 A66.1）中的一种感染。我们确定，细菌感染后，病毒滴度最初反弹，然后缓慢下降。细菌滴度迅速升至高水平并保持在高水平。我们使用动力学模型来探索耦合相互作用并研究主要控制机制。我们假设，在细菌存在的情况下，由于受感染细胞的病毒释放增强，病毒滴度会反弹，并且由于肺泡巨噬细胞损伤，细菌滴度会增加。动力学受初始细菌剂量影响，但不受流感 1918 PB1-F2 蛋白表达的影响。我们的模型提供了一个框架来研究共感染期间病原体的相互作用，并揭示基于接种量和菌株的动态差异。流感病毒感染者通常会同时感染细菌病原体，因此发病率和死亡率显着增加。更好地了解这些病原体如何彼此相互作用以及与宿主相互作用至关重要。在这里，我们使用受感染小鼠的数据以及数学模型和定量分析来了解每种病原体如何影响另一种病原体，以及 1918 年流感 PB1-F2 蛋白以及细菌菌株和剂量如何影响共感染动力学。我们发现，当肺炎链球菌存在时，流感病毒滴度会增加，并且当流感存在时，细菌会迅速建立和生长。我们的模型和分析表明，流感感染降低了肺泡巨噬细胞的细菌清除能力，随后的肺炎链球菌感染增强了受感染细胞的病毒释放。这些结果为流感混合感染的机制以及流感和肺炎链球菌菌株发病机制的差异提供了新的见解。
Secondary bacterial infections are a leading cause of illness and death during epidemic and pandemic influenza. Experimental studies suggest a lethal synergism between influenza and certain bacteria, particularly Streptococcus pneumoniae, but the precise processes involved are unclear. To address the mechanisms and determine the influences of pathogen dose and strain on disease, we infected groups of mice with either the H1N1 subtype influenza A virus A/Puerto Rico/8/34 (PR8) or a version expressing the 1918 PB1-F2 protein (PR8-PB1-F2(1918)), followed seven days later with one of two S. pneumoniae strains, type 2 D39 or type 3 A66.1. We determined that, following bacterial infection, viral titers initially rebound and then decline slowly. Bacterial titers rapidly rise to high levels and remain elevated. We used a kinetic model to explore the coupled interactions and study the dominant controlling mechanisms. We hypothesize that viral titers rebound in the presence of bacteria due to enhanced viral release from infected cells, and that bacterial titers increase due to alveolar macrophage impairment. Dynamics are affected by initial bacterial dose but not by the expression of the influenza 1918 PB1-F2 protein. Our model provides a framework to investigate pathogen interaction during coinfections and to uncover dynamical differences based on inoculum size and strain. Influenza virus infected individuals often become coinfected with a bacterial pathogen and, consequently, morbidity and mortality are significantly increased. A better understanding of how these pathogens interact with each other and the host is of key importance. Here, we use data from infected mice together with mathematical modeling and quantitative analyses to understand how each pathogen influences the other, and how the 1918 influenza PB1-F2 protein and the bacterial strain and dose contribute to coinfection kinetics. We find that influenza viral titers increase when Streptococcus pneumoniae is present and that the bacteria establish and grow rapidly when influenza is present. Our model and analyses suggest that the influenza infection reduces the bacterial clearance ability of alveolar macrophages and that the subsequent S. pneumoniae infection enhances viral release from infected cells. These results provide new insights into the mechanisms of influenza coinfection and the differences in pathogenesis of influenza and S. pneumoniae strains.
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影响因子：
168.9
作者：
Gubareva, LV;Kaiser, L;Hayden, FG
通讯作者：
Hayden, FG
影响因子：
6.4
作者：
Iverson, Amy R.;Boyd, Kelli L.;McCullers, Jonathan A.
通讯作者：
McCullers, Jonathan A.
DOI：
10.1073/pnas.1019378108
发表时间：
2011-03-29
影响因子：
11.1
作者：
Ichinohe, Takeshi;Pang, Iris K.;Iwasaki, Akiko
通讯作者：
Iwasaki, Akiko
影响因子：
15.3
作者：
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通讯作者：
Hussell, Tracy
影响因子：
82.9
作者：
Chen, WS;Calvo, PA;Yewdell, JW
通讯作者：
Yewdell, JW