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.

Mitochondria are crucial in the execution of programmed cell death and therefore an important line of defense against various insults such as pathogenic infections. Hence some proteins of important human pathogenic viruses do even localize within mitochondria to interfere with apoptosis [26] . Another important cellular factor for viral countermeasures against cellular defense mechanisms is the tumor-suppressor protein p53 as an important orchestrator of those intertwined and interdependent mitochondrial functions [27] . The data presented in this paper indicate that RV-induced apoptosis as well as its cell-culture adaptation involve a balance between nuclear and extranuclear functions of p53. Additionally, RV induces release of pro-apoptotic proteins from mitochondria and nuclear translocation of Cyp40. The presented data are summarized in Figure 9 as (B) Immunofluorescence analysis was performed with anti-p53 antibody to assess intracellular distribution of p53 (shown in red). RV infection was visualized with anti-E1 antibody (shown in green). Nuclear DNA is shown in blue. Pink colour indicates overlap areas; (C) Alteration of the mRNA expression level of p21 after infection with RV strains, Therien and Wb-12. The mRNA expression level was determined at 1, 2 and 3 dpi relative to the corresponding mock sample (set at 100%). Scale bar, 20 µm. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001