Ebola virus infection modeling and identifiability problems

被引:36
作者
Van Kinh Nguyen [1 ,2 ]
Binder, Sebastian C. [2 ,3 ]
Boianelli, Alessandro [1 ,2 ]
Meyer-Hermann, Michael [2 ,3 ,4 ]
Hernandez-Vargas, Esteban A. [1 ,2 ]
机构
[1] Helmholtz Ctr Infect Res, Dept Syst Immunol, Syst Med Infect Dis, D-38124 Braunschweig, Germany
[2] Helmholtz Ctr Infect Res, Braunschweig Integrated Ctr Syst Biol, D-38124 Braunschweig, Germany
[3] Helmholtz Ctr Infect Res, Dept Syst Immunol, D-38124 Braunschweig, Germany
[4] Tech Univ Carolo Wilhelmina Braunschweig, Inst Biochem Biotechnol & Bioinformat, D-38106 Braunschweig, Germany
关键词
Ebola; mathematical modeling; kinetics; viral dynamics; identifiability; EBOV; GLOBAL OPTIMIZATION; DYNAMICS; KINETICS;
D O I
10.3389/fmicb.2015.00257
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页数:11
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