BAVARIAN

Borna disease virus (BoDV), a single-stranded RNA virus of negative polarity, has puzzled researchers for decades, because of its neurotropism and non-cytolytic multiplication strategy. Its recent recognition as a zoonotic agent causing severe encephalitis and brain dysfunction has provided further impetus for increasing our knowledge on this enigmatic pathogen. 

In this context, the Bavarian project aims at providing an integrative and multiscale vision of the BoDV replication complex. Our multi-pronged proposal will describe the structural organization and explore the BoDV replication complex modus operandi within infected cells. To tackle these questions, our three teams will combine their expertise, implementing cutting-edge structural biology, biochemistry, virology and neuronal functional assays. 

Our complementary approaches will allow a fine characterization of: 

(i) the architecture of the BoDV replicative machinery, 

(ii) its viral-host polypeptides interplays and 

(iii) the impact of altering the viral replication on viral fitness, neuronal epigenetics and function. 

Our project will provide an unmatched deciphering of BoDV pathogenic mechanisms and, in a broader view, will represent a breakthrough in the field of RNA virus family evolutionary mechanisms. Indeed, Bavarian will focus on the only non-retroviral RNA virus known so far that needs to interact with the host DNA genome to persist and proliferate.