Characterization of Borna disease virus-mediated antagonization of the cellular interferon system

• Applicant: Privatdozent Dr. Thorsten Wolff
• Subject Area: Virology
• Term: from 2003 to 2006
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5395208

The type I interferon (IFN) system is one of the most important mediators of the innate response of vertebrates toward virus infections. It is triggered most likely by double-strand (ds) RNA produced during viral replication which is recognized by cellular sensor proteins. The neurotropic Borna Disease Virus (BDV) possesses a non-segmented negative strand RNA genome that is replicated in the cell nucleus. Although BDV replication leads potentially to the production of dsRNA, the virus can successfully establish persistent, non-cytolytic infections of tissue culture cells and in certain animal species. Thus, BDV can resist or avoid the deleterious effects of the innate response, but the mechanism of this escape is unknown. I have discovered that a BDV infection suppresses the ability of cells to respond to stimuli that activate the IFN system. This finding demonstrates that BDV expresses a gene product(s) that interferes with the signaling processes required for induction of type I IFN genes. Reporter gene assays have indicated that at least one BDV-specific protein exhibits such an acitivity. The goals of this project are to identify and to characterize the precise IFN antagonistic protein of BDV and to decipher the mechanisms underlying this activity. It is expected that we will gain novel mechanistical insights how Borna viruses and possibly other viral pathogens counteract the innate response and cause disease.

• DFG Programme: Research Grants