Dynamic model of the pathogenesis of Mengo virus infection in mice.

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.