Immunorecognition of viral nucleic acids in the cytosol

• Applicant: Professor Dr. Winfried Barchet
• Subject Area: Immunology
• Term: from 2007 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 33259174

At present, protective and long-lasting T cell immunity can only be achieved with viral vaccines. Now the concept emerges that receptors of the innate immune system are triggered by unique features of viral nucleic acids. In preliminary work we have shown that immune cells rely on toll-like receptors 3, 7/8 and 9 to recognize viral double stranded (ds)RNA, single stranded RNA and DNA, respectively. In addition, the helicases RIG-I and MDA-5 are widely expressed, and allow the detection of intracellularly replicating virus also by non-immune cells. Through the generation of gene deficient mice we were able to demonstrate that MDA-5 is required for the detection of picornaviruses and synthetic dsRNA. The goal of this proposal is to define the natural, as well as optimized synthetic ligands for MDA-5. This may allow for the first time to harness the mechanisms of intracellular virus detection for the induction of effective T cell responses, and thus to substitute attenuated viruses in vaccines. The efficacy of these virus-like vaccines will be assessed in animal models of chronic viral infection and of spontaneous tumors; these studies will form the basis for future therapeutic use.

• DFG Programme: Independent Junior Research Groups
• International Connection: Belgium
• Participating Persons: Professor Dr. Thomas Michiels; Professor Dr. Friedemann Weber