Young research goup around Cluster Member Stephanie Jung shows how danger signaling is amplified in Influenza A-virus infected cells.
Influenza virus-induced acute respiratory infections occur in all parts of the world and represent a constant disease-burden. While the seasonal epidemic outbreaks are caused by Influenza-subtypes A and B, only Influenza-A strains are reported to have caused pandemic spreads. Overall, Influenza-A infections account for 250,000 to 300,000 deaths p.a.
To protect us from microbial threats, the innate immune system provides several immune sensing receptors. These recognize foreign microbial molecules and induce an immunological response. RNA-viruses like Influenza-A and Hepatitis-C are detected by the intracellular receptor RIG-I (retinoic acid inducible gene I). RIG-I binds to double-stranded viral RNA and hairpin structures of viral genomes. Upon activation, the receptor multimerizes and ultimately induces the cellular release of antiviral cytokines.
In a previous publication, Stephanie Jung and colleagues already described the role of endogenous RNA in an amplified RIG-I activation: Recognition of viral RNA by oligoadenylate synthase leads to activation of RNase L, which cleaves endogenous ribosomal RNAs. The resulting fragment acts as endogenous RIG-I ligand (eRL) and thereby amplifies the RIG-I mediated response to the viral thread.
Stephanie Jung and her team now provide evidence that eRL is generated in Influenza-A infected cells. Further they could show that the activation of RIG-I by eRL is independent of the direct recognition of viral RNAs by the receptor. The work thereby provides the foundation for further research on the physiological function of eRLs and their role in other viral infections.
Remarkably, the paper was published only a few months into first-author Julia Steinbergs PhD project, who started her work with Stephanie Jung in April 2021. “Sometimes things just run perfectly – even in the lab” Julia states. It is important to enable young scientists to publish early on during their PhD, Stephanie Jung is convinced. “With her first publication in hand, Julia can now pursue her main project with the maximum freedom possible”.
It is also the first publication for Stephanie Jung as Junior Professor for Cellular Virology and member of the Cluster of Excellence Immunosensation2. As group leader at the institute of Cardiovascular Immunology, her research is focused on the identification of immune-activating viral RNAs and the role of extracellular vesicles in viral infections.
Participating institutions and funding
The project was funded by the German Research Foundation (DFG) under the Germany’s Excellence Strategy – EXC2151 – 390873048.
Publication
Julia Steinberg, Timo Wadenpohl, Stephanie Jung: The Endogenous RIG-I Ligand Is Generated in Influenza A-Virus Infected Cells. Viruses. https://www.mdpi.com/1999-4915/13/8/1564
Contact
University Bonn
University Hospital Bonn