Guthke R, Veckenstedt A, Güttner J, Stracke R, Bergter F
Central Institute of Microbiology and Experimental Therapy, Academy of Sciences of the German Democratic Republic, Jena.
Acta Virol. 1987 Aug;31(4):307-20.
A mathematical model of the pathogenesis of experimental Mengo virus infection in mice has been developed and fitted using kinetic data of both virus multiplication in different organs and mortality. The behaviour of the model proved to be bistable. In contrast to the widely accepted hypothesis that an acutely virus-infected host dies when virus replication has attained a critical level in the main target organ, the present results showed the following: the maximum virus titre in brain, the main target organ, has been reached already 24 hr post infection (p.i.) but the animals began to die since 60 hr. Hence, it was postulated and confirmed by a good model fit to the experimental data that the so-called AUC (area under the curve) of the virus multiplication kinetics may be a critical quantity. From this finding a hypothesis was deduced assuming that in the presence of high amounts of the virus the antiviral effect of IFN wanes with time. Since this process accounts for death, it may be a potential target of antiviral therapy.
已经建立了小鼠实验性 Mengo 病毒感染发病机制的数学模型，并使用不同器官中病毒增殖的动力学数据和死亡率进行了拟合。该模型的行为被证明是双稳态的。与广泛接受的假设（即急性病毒感染的宿主在主要靶器官中病毒复制达到临界水平时死亡）相反，目前的结果表明：主要靶器官大脑中的最大病毒滴度在感染后 24 小时就已达到，但动物从 60 小时开始死亡。因此，通过对实验数据的良好模型拟合推测并证实，病毒增殖动力学的所谓 AUC（曲线下面积）可能是一个关键量。基于这一发现推导了一个假设，即假设在存在大量病毒的情况下，IFN 的抗病毒作用会随时间减弱。由于这个过程导致死亡，它可能是抗病毒治疗的一个潜在靶点。
