论文标题

体外量化埃博拉病毒复制动力学

Quantification of Ebola virus replication kinetics in vitro

论文作者

Liao, Laura E., Carruthers, Jonathan, Smither, Sophie J., Team, CL4 Virology, Weller, Simon A., Williamson, Diane, Laws, Thomas R., Garcia-Dorival, Isabel, Hiscox, Julian, Holder, Benjamin P., Beauchemin, Catherine A. A., Perelson, Alan S., Lopez-Garcia, Martin, Lythe, Grant, Barr, John, Molina-Paris, Carmen

论文摘要

数学建模已成功地用于提供许多病毒感染的定量描述,但是对于需要生物安全4级实验设施的埃博拉病毒,建模可以起着至关重要的作用。埃博拉病毒建模工作主要集中在体内病毒动力学上,例如在动物模型中,以帮助开发抗病毒药和疫苗。但是,到目前为止,这些研究尚未对感染周期产生详细的规范,这可以提供病毒动力学的基本描述,从而更深入地了解其临床表现。在这里,我们在体外获得了埃博拉病毒感染的多种实验数据集,然后利用贝叶斯推理方法在感染的数学模型中充分识别参数。我们的结果提供了有关感染细胞在日食阶段(感染和病毒产生开始之间的时期)以及感染性病毒率失去感染性的速度的时间的见解。我们建议如何在将来的模型中使用这些结果来描述有缺陷的干扰颗粒,这是一种新兴的替代治疗。

Mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the Ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. Ebola modelling efforts have primarily focused on in vivo virus kinetics, e.g., in animal models, to aid the development of antivirals and vaccines. But, thus far, these studies have not yielded a detailed specification of the infection cycle, which could provide a foundational description of the virus kinetics and thus a deeper understanding of their clinical manifestation. Here, we obtain a diverse experimental data set of the Ebola infection in vitro, and then make use of Bayesian inference methods to fully identify parameters in a mathematical model of the infection. Our results provide insights into the distribution of time an infected cell spends in the eclipse phase (the period between infection and the start of virus production), as well as the rate at which infectious virions lose infectivity. We suggest how these results can be used in future models to describe co-infection with defective interfering particles, which are an emerging alternative therapeutic.

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