Higher Level of Replication Efficiency of 2009 (H1N1) Pandemic Influenza Virus than Those of Seasonal and Avian Strains: Kinetics from Epithelial Cell Culture and Computational Modeling
Higher Level of Replication Efficiency of 2009 (H1N1) Pandemic Influenza Virus than Those of Seasonal and Avian Strains: Kinetics from Epithelial Cell Culture and Computational Modeling
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DOI：
10.1128/jvi.01722-10
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发表时间：
2011-01-01
影响因子：
5.4
通讯作者：
Koster, Frederick
中科院分区：
文献类型：
--
作者：
Mitchell, Hugh;Levin, Drew;Koster, Frederick
甲型流感病毒的致病性和传播可能部分取决于人类细胞的复制效率，这是复杂的病毒与宿主相互作用的净影响。H5N1禽流感病毒株、H1N1季节性流感病毒株和H1N1 2009年大流行性流感病毒株通过在相对较低的病毒颗粒/细胞比率的气液界面培养中感染人分化的支气管上皮细胞来比较。用微分方程式和计算模型描述了3株菌株的体外动力学行为。通过对实验数据的拟合对模型进行了标定，以估计难以测量的参数。两个模型都发现，p(每细胞的病毒粒子产生率)和R-0(感染通过单层传播的指数)的相对值存在显著差异，毒株的值按以下顺序排列(从大到小)：大流行毒株，其次是季节性毒株，然后是禽类毒株，正如预期的那样。在微分方程式模型中，将病毒和细胞群体很好地混合在一起，所有3个菌株的R-0和p都成比例变化，这与生产力的主要作用是一致的。在空间显式计算模型中，R-0和p也成比例变化，只是大流行毒株的R-0减少了，这与包括粘液和旁分泌抗病毒作用在内的多种宿主防御所施加的限制病毒传播一致。这一协同实验-计算策略为识别和表型潜在的大流行毒株提供了相关参数。
The pathogenicity and transmission of influenza A viruses are likely determined in part by replication efficiency in human cells, which is the net effect of complex virus-host interactions. H5N1 avian, H1N1 seasonal, and H1N1 2009 pandemic influenza virus strains were compared by infecting human differentiated bronchial epithelial cells in air-liquid interface cultures at relatively low virus particle/cell ratios. Differential equation and computational models were used to characterize the in vitro kinetic behaviors of the three strains. The models were calibrated by fitting experimental data in order to estimate difficult-to-measure parameters. Both models found marked differences in the relative values of p, the virion production rate per cell, and R-0, an index of the spread of infection through the monolayer, with the values for the strains in the following rank order (from greatest to least): pandemic strain, followed by seasonal strain, followed by avian strain, as expected. In the differential equation model, which treats virus and cell populations as well mixed, R-0 and p varied proportionately for all 3 strains, consistent with a primary role for productivity. In the spatially explicit computational model, R-0 and p also varied proportionately except that R-0 derived for the pandemic strain was reduced, consistent with constrained viral spread imposed by multiple host defenses, including mucus and paracrine antiviral effects. This synergistic experimental-computational strategy provides relevant parameters for identifying and phenotyping potential pandemic strains.