Activation of the Mitochondrial Apoptotic Signaling Platform during Rubella Virus Infection

Claus, Claudia; Manssen, Lena; Hübner, Denise; Roßmark, Sarah; Bothe, Viktoria; Petzold, Alice; Große, Claudia; Reins, Mareen; Mankertz, Annette; Frey, Teryl K.; Liebert, Uwe G.

There is a well-defined balance between cell survival and cell-death induction, and consequently the cellular responses to a viral infection are interconnected with the resulting viral countermeasures. Already minor changes can evoke alterations of cellular antiviral activities, as shown in this paper by the increase in p53 nuclear expression after inhibiting mitochondrial shuttling of p53 with PFTµ. CPE induction after RV infection is only observed after infection of susceptible cell lines such as Vero and RK13 [2] . It is especially noteworthy that RV-induced apoptosis is detectable in human primary differentiated, nonproliferative cells, but not in proliferative fetal cells [43] . This strengthens the cellular context dependency of RV-associated apoptotic processes, which might be due to differences in cellular signaling pathways or to differences in the anti-viral response provoked by RV in these cell lines. The identification of cellular factors specific for RV-induced cell death as outlined in this study will help to address and delineate this cell line-dependency as identified factors can be specifically examined in their cellular context. Clinical isolates can be regarded as a tool for identification of viral and cellular components that contribute to RV cell-culture adaptation. Future experiments will be aimed at elucidating the interplay of RV strains with nuclear and extranuclear p53 pools and how a virus coordinates cellular functions to its own advantage.