Quantification of Ebola virus replication kinetics in vitro.
Quantification of Ebola virus replication kinetics in vitro.
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DOI：
10.1371/journal.pcbi.1008375
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发表时间：
2020-11
影响因子：
4.3
通讯作者：
Molina-París C
中科院分区：
文献类型：
--
作者：
Liao LE;Carruthers J;Smither SJ;CL4 Virology Team;Weller SA;Williamson D;Laws TR;García-Dorival I;Hiscox J;Holder BP;Beauchemin CAA;Perelson AS;López-García M;Lythe G;Barr JN;Molina-París C
数学建模已成功用于对许多病毒感染进行定量描述，但对于埃博拉病毒（其实验需要生物安全四级设施），建模可发挥关键作用。埃博拉病毒的建模工作主要集中在体内病毒动力学方面，例如在动物模型中，以辅助抗病毒药物和疫苗的研发。但是，到目前为止，这些研究尚未对感染周期作出详细说明，而这一说明可以为病毒动力学提供基础描述，从而更深入地了解其临床表现。在此，我们获取了埃博拉病毒体外感染的多样实验数据集，然后利用贝叶斯推断方法全面确定感染数学模型中的参数。我们的结果深入了解了受感染细胞在隐蔽期（感染到病毒开始产生之间的时期）所花费的时间分布，以及感染性病毒粒子失去传染性的速率。我们提出这些结果如何可用于未来的模型中，以描述与缺陷干扰颗粒的共感染，这是一种新兴的替代疗法。
两次最致命的埃博拉病毒疫情都发生在过去五年内，其中一次疫情仍在持续。数学建模已经对人群层面的疾病传播以及抗病毒治疗在埃博拉病毒感染动物中的效果提供了见解。然而，仍然缺乏对复制周期的定量描述。在此，我们报告了一组涉及埃博拉病毒埃克兰株感染的体外实验结果。通过对一个数学模型进行参数化，我们能够确定对复制周期时长、感染性爆发规模以及病毒清除率的可靠估计。
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 virus 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 virus 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. The two deadliest Ebola virus epidemics have both occurred in the past five years, with one of these epidemics still ongoing. Mathematical modelling has already provided insights into the spread of disease at the population level as well as the effect of antiviral therapy in Ebola virus-infected animals. However, a quantitative description of the replication cycle is still missing. Here, we report results from a set of in vitro experiments involving infection with the Ecran strain of Ebola virus. By parameterizing a mathematical model, we are able to determine robust estimates for the duration of the replication cycle, the infectious burst size, and the viral clearance rate.
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影响因子：
4.6
作者：
Beauchemin CA;Miura T;Iwami S
通讯作者：
Iwami S
DOI：
10.1056/nejmoa1604330
发表时间：
2016-10-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
PREVAIL II Writing Group;Multi-National PREVAIL II Study Team;Davey RT Jr;Dodd L;Proschan MA;Neaton J;Neuhaus Nordwall J;Koopmeiners JS;Beigel J;Tierney J;Lane HC;Fauci AS;Massaquoi MBF;Sahr F;Malvy D
通讯作者：
Malvy D
影响因子：
5.2
作者：
Iwami S;Sato K;De Boer RJ;Aihara K;Miura T;Koyanagi Y
通讯作者：
Koyanagi Y
影响因子：
3.7
作者：
Gonzalez-Parra, Gilberto;De Ridder, Filip;Dobrovolny, Hana M.
通讯作者：
Dobrovolny, Hana M.
DOI：
10.1007/978-1-4939-7116-9_9
发表时间：
2017-01-01
期刊：
EBOLAVIRUSES
影响因子：
--
作者：
Biedenkopf, Nadine;Hoenen, Thomas
通讯作者：
Hoenen, Thomas