Modellgestützte Analyse des Einflusses von Influenzaviren mit defekten Genom-segmenten auf die Virusreplikation während der Produktion von Influenza-Impfstoffen

Defective interfering particles (DIPs) of the influenza virus are non-infectious particles, which can only replicate in cells that are co-infected with a wild-type virus. Because of an advantage in replication, DIPs strongly interfere with virus production in these coinfections and dramatically reduce virus yields during cell culture-based vaccine production. To examine the interference of DIPs systematically, we developed a mathematical model, which describes the replication of DIPs and wt particles in a single co-infected cell. Intriguingly, our results show a significant decrease in total viral protein production leading to a shortage of both the nucleoprotein (NP) and the viral polymerase complex. The low number of these two proteins can limit the replication of viral genome copies, thereby impairing the release of progeny virions. We identified three major factors affecting DIP replication and virus release: (i) the length of the defective segment, (ii) the time of co-infection and (iii) the number of infecting particles. Furthermore, we propose that there is only a small time window after wt-infection, in which the co-infection with DIPs alters viral replication. Hence, our newly developed model provides an ideal basis for studying the intracellular dynamics of viral genome segments and viral proteins upon co-infection with defective interfering particles