Immunomodulatory RNA species regulating innate immunity

The recognition of virus-associated RNAs and viral genomes as pathogen-associated molecular patterns (PAMPs) plays a central role in the immune response to viral infections. Nucleic acid PAMPs activate subgroups of DNA and RNA-detecting pattern recognition receptors (PRRs), which can distinguish between cellular and non-cellular components. Their activation leads to the induction of the antiviral state, which is characterized by the expression of interferon-stimulated genes (ISGs). To circumvent innate sensing and ISG-mediated suppression of viral replication, viruses like HBV have developed immune-evasion mechanisms (Jung et al, World Journal of Gastroenterology 2020 and Walter et al, Pathogens 2022). However, in many viral infections the nature of the immunomodulatory RNA species is still largely unknown. We recently identified the nature of an immune-activating cellular RNA ligand (Jung et al, Nucleic Acid research 2020; Steinberg et al, Viruses 2021). Our future research focus is on identifying specific viral and cellular RNA pattern modifying the immune response (Nicolai et al, IJMS 2022).

Extracellular vesicles in viral infections

EVs are actively released by various cell types and contain snapshot-like information about the cell status at the time of their biogenesis. EVs can exert immunomodulatory effects by acting as signalling vehicles and transporting cellular cargo between the cell of origin and the recipient cell. In their size, density, and origin, EVs show similarities to viruses and may also shuttle viral or virus-induced components, thereby contributing to infection.

We recently showed that Hepatitis D Virus (HDV) monoinfection, which does not induce virus release in the absence of Hepatitis B Virus (HBV), mediates the release of immune activating EVs (Jung et al, Matters 2020). This is the first publication ever to establish a link between EVs and HDV. Furthermore, we developed an essential method to separate virions and extracellular vesicles (Jung et al, Journal of extracellular vesicles 2020). Using this method, a clear distinction between virus and EV-mediated effects under natural conditions is possible for the first time. Our future research will investigate both pro- and antiviral effects of EVs in diverse viral infections (we are not limited to HBV and HDV anymore) under natural conditions.

Development of RNA and EV methods

In addition to our interdisciplinary basic research, we also have a strong affinity for developing new methods to advance research into new subject areas. Whether it is the separation of EVs and virions, the development of a new method for highly economical EV mass purification, or the targeted loading of EVs – perhaps we have developed what you need? We are also happy to use these methodologies for joint projects with colleagues from other departments.