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埃博拉病毒感染建模与可识别性问题。

Ebola virus infection modeling and identifiability problems.

作者信息

Nguyen Van Kinh, Binder Sebastian C, Boianelli Alessandro, Meyer-Hermann Michael, Hernandez-Vargas Esteban A

机构信息

Systems Medicine of Infectious Diseases, Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research Braunschweig, Germany.

Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research Braunschweig, Germany.

出版信息

Front Microbiol. 2015 Apr 9;6:257. doi: 10.3389/fmicb.2015.00257. eCollection 2015.

Abstract

The recent outbreaks of Ebola virus (EBOV) infections have underlined the impact of the virus as a major threat for human health. Due to the high biosafety classification of EBOV (level 4), basic research is very limited. Therefore, the development of new avenues of thinking to advance quantitative comprehension of the virus and its interaction with the host cells is urgently needed to tackle this lethal disease. Mathematical modeling of the EBOV dynamics can be instrumental to interpret Ebola infection kinetics on quantitative grounds. To the best of our knowledge, a mathematical modeling approach to unravel the interaction between EBOV and the host cells is still missing. In this paper, a mathematical model based on differential equations is used to represent the basic interactions between EBOV and wild-type Vero cells in vitro. Parameter sets that represent infectivity of pathogens are estimated for EBOV infection and compared with influenza virus infection kinetics. The average infecting time of wild-type Vero cells by EBOV is slower than in influenza infection. Simulation results suggest that the slow infecting time of EBOV could be compensated by its efficient replication. This study reveals several identifiability problems and what kind of experiments are necessary to advance the quantification of EBOV infection. A first mathematical approach of EBOV dynamics and the estimation of standard parameters in viral infections kinetics is the key contribution of this work, paving the way for future modeling works on EBOV infection.

摘要

近期埃博拉病毒(EBOV)感染的爆发凸显了该病毒对人类健康构成的重大威胁。由于EBOV的生物安全等级较高(4级),基础研究非常有限。因此,迫切需要开拓新的思路,以加深对该病毒及其与宿主细胞相互作用的定量理解,从而攻克这种致命疾病。EBOV动态的数学建模有助于从定量角度解释埃博拉感染动力学。据我们所知,目前仍缺乏一种用于揭示EBOV与宿主细胞之间相互作用的数学建模方法。本文采用基于微分方程的数学模型来描述EBOV与野生型非洲绿猴肾细胞(Vero细胞)在体外的基本相互作用。针对EBOV感染,估计了代表病原体传染性的参数集,并与流感病毒感染动力学进行了比较。EBOV感染野生型Vero细胞的平均感染时间比流感感染要慢。模拟结果表明,EBOV较慢的感染时间可通过其高效复制得到弥补。本研究揭示了几个可识别性问题,以及推进EBOV感染定量研究所需的实验类型。EBOV动态的首个数学方法以及病毒感染动力学标准参数的估计是本研究的关键贡献,为未来关于EBOV感染的建模工作铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff3d/4391033/a8d904f9b2e2/fmicb-06-00257-g0001.jpg

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