The inflammatory response to influenza A virus (H1N1): An experimental and mathematical study.
The inflammatory response to influenza A virus (H1N1): An experimental and mathematical study.
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DOI：
10.1016/j.jtbi.2015.03.017
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发表时间：
2015-06-07
影响因子：
2
通讯作者：
Clermont, Gilles
中科院分区：
文献类型：
--
作者：
Price, Ian;Mochan-Keef, Ericka D.;Swigon, David;Ermentrout, G. Bard;Lukens, Sarah;Toapanta, Franklin R.;Ross, Ted M.;Clermont, Gilles
流感感染的死亡率仍然是一个全球性的公共卫生问题，宿主的炎症反应导致与原发感染相关的死亡。基于常微分方程（ODE）形式主义，开发了一个计算模型，用于对甲型流感病毒的宿主内反应，合并了对病毒的炎症、先天、适应性和体液反应，并将感染的严重程度、炎症反应和死亡率联系起来。使用来自感染H1N1流感病毒株A/PR/8/34的成年BALB/c小鼠的亚致死和致死剂量的密集细胞因子和细胞数据校准模型。使用贝叶斯推断和集成模型方法量化模型参数和疾病机制的不确定性，该方法生成生存概率预测，定义为呼吸道上皮的病毒清除和恢复。该集合恢复了病毒暴露程度与生存期之间的预期关系，并提出了主要负责生存的机制，这可以指导免疫调节干预措施的发展，以取代目前的抗病毒治疗。该模型用于从可用数据外推群体的存活曲线及其对初始病毒等分试样的依赖性。此外，该模型使我们能够说明控制炎症对流感存活的积极影响。
Mortality from influenza infections continues as a global public health issue, with the host inflammatory response contributing to fatalities related to the primary infection. Based on Ordinary Differential Equation (ODE) formalism, a computational model was developed for the in-host response to influenza A virus, merging inflammatory, innate, adaptive and humoral responses to virus and linking severity of infection, the inflammatory response, and mortality. The model was calibrated using dense cytokine and cell data from adult BALB/c mice infected with the H1N1 influenza strain A/PR/8/34 in sublethal and lethal doses. Uncertainty in model parameters and disease mechanisms was quantified using Bayesian inference and ensemble model methodology that generates probabilistic predictions of survival, defined as viral clearance and recovery of the respiratory epithelium. The ensemble recovers the expected relationship between magnitude of viral exposure and the duration of survival, and suggests mechanisms primarily responsible for survival, which could guide the development of immunomodulatory interventions as adjuncts to current anti-viral treatments. The model is employed to extrapolate from available data survival curves for the population and their dependence on initial viral aliquot. In addition, the model allows us to illustrate the positive effect of controlled inflammation on influenza survival.
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影响因子：
3.7
作者：
Dobrovolny HM;Reddy MB;Kamal MA;Rayner CR;Beauchemin CA
通讯作者：
Beauchemin CA
影响因子：
2
作者：
Beauchemin, Catherine
通讯作者：
Beauchemin, Catherine
影响因子：
5.4
作者：
Hernandez-Vargas, Esteban A.;Wilk, Esther;Meyer-Hermann, Michael
通讯作者：
Meyer-Hermann, Michael
DOI：
10.1073/pnas.0904846106
发表时间：
2009-07-07
影响因子：
11.1
作者：
Day, Judy;Friedman, Avner;Schlesinger, Larry S.
通讯作者：
Schlesinger, Larry S.
影响因子：
2
作者：
Kumar, R;Clermont, G;Chow, CC
通讯作者：
Chow, CC