Project B1: Alexandra Birzer (Alumna)

Virology

Head of Institute:
Prof. Dr. med. Klaus Überla

Analyses of the IL-6 signaling pathway in HSV-1-infected dendritic cells and characterization of HSV-1-derived L-particles

The human organism is protected from the continuous threat of pathogens by the immune system. Dendritic cells (DCs) are the most potent antigen presenting cells and play a pivotal role in the induction of protective adaptive immune responses against such pathogens. Thus, DCs represent an interesting target for virus-induced immune-evasion strategies. In this respect, herpes simplex virus type 1 (HSV-1) has evolved several immune evasion mechanism in order to hamper the induction of a potent antiviral immune response by interfering with DC biology.

Since the IL-6 signaling pathway is important for the induction of anti-viral immune responses, this pathway is frequently targeted by specific viruses, including Enterovirus 71 and influenza A virus. To investigate, if and how also herpesviruses interfere with the IL-6 signaling pathway, we analyzed the expression of IL6Rα and STAT3 during HSV-1 infection.

Thereby we found out that HSV-1 modulates the expression levels of IL6Rα as well as STAT3 of directly-infected mDCs. Regarding IL6Rα, not only directly-infected but also uninfected “bystander” mDCs displayed reduced IL6Rα protein and mRNA expression levels, however, in a timely-delayed manner. Our work demonstrates that HSV-1-derived L-particles transport viral proteins to uninfected “bystander” DCs, to induce the downmodulation of functionally important proteins, such as IL6Rα, and thereby hamper DC mediated antiviral immune responses.

 
Alexandra Birzer,
Associated PhD student (Alumna)