Department of Mathematics, New Mexico Tech, Socorro, NM, United States.
Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX, United States.
Virology. 2018 Oct;523:129-139. doi: 10.1016/j.virol.2018.07.027. Epub 2018 Aug 23.
Experimental results in vitro and in animal models are used to guide researchers in testing vaccines or treatment in humans. However, viral kinetics are different in vitro, in animals, and in humans, so it is sometimes difficult to translate results from one system to another. In this study, we use a mathematical model to fit experimental data from multiple cycle respiratory syncytial virus (RSV) infections in vitro, in african green monkey (AGM), and in humans in order to quantitatively compare viral kinetics in the different systems. We find that there are differences in viral clearance rate, productively infectious cell lifespan, and eclipse phase duration between in vitro and in vivo systems and among different in vivo systems. We show that these differences in viral kinetics lead to different estimates of drug effectiveness of fusion inhibitors in vitro and in AGM than in humans.
体外和动物模型中的实验结果被用于指导研究人员在人体中测试疫苗或治疗方法。然而,病毒动力学在体外、动物和人体中是不同的,因此有时很难将结果从一个系统转换到另一个系统。在这项研究中,我们使用数学模型来拟合来自体外、非洲绿猴(AGM)和人体中多次循环呼吸道合胞病毒(RSV)感染的实验数据,以便定量比较不同系统中的病毒动力学。我们发现,在体外和体内系统之间以及不同的体内系统之间,病毒清除率、有生产力的感染细胞寿命和潜伏期持续时间存在差异。我们表明,这些病毒动力学的差异导致了在体外和 AGM 中对融合抑制剂的药物有效性的估计与在人体中不同。