Analysis of Interferon Induction in Mammalian Cells during Influenza Virus Production

The annual appearance of new influenza strains differing in antigenic properties and virulence from former viruses demands annual adaptation of existing influ-enza vaccine production processes to the new strains. This was seen also in a Madin-Darby canine kidney (MDCK) cell culture based influenza production process where varying yields and differences in dynamics of virus replication for a set of human influenza virus strains were observed. Strain dependence of virus host cell interactions, especially induction or suppression of the cellular type I interferon (IFN) response could be related to this. Therefore it was analyzed, whether the induction of type I IFN and subsequent expression of antiviral genes can explain differences in virus yield and replication dynamics. We used qRT-PCR and luciferase reporter assays to determine the expression levels of IFN-beta and Mx1, an interferon stimulated antiviral gene, in MDCK cells. Cells were infected with a set of different influenza strains known to vary in replication behaviour. All strains tested showed significant induction of IFN-beta, but expression levels, as well as kinetics of induction and amount of resulting Mx1 expression varied from strain to strain. Even between identical subtypes but with a different passage history, e.g. the same subtype purchased from NIBSC and Robert Koch Institute (RKI), differences could be identified. The low yield “NIBSC” strain showed fast and strong induction of IFN-beta and Mx1, whereas the high yield “RKI” strain exhibited lower expression levels and delayed induc-tion of IFN-beta and Mx1. Taken together with data of other influenza strains, these results suggest a correlation of the level of interferon induction, replication dynamics, and virus yield