Genome trimming by Borna disease viruses: Viral replication control or escape from cellular surveillance?

Abstract.

Persistence of RNA viruses is frequently associated with non-uniform terminal nucleotide deletions at both ends of the viral genome, which are believed to restrict viral replication and transcription during persistent infection. Borna disease virus (BDV), a negative strand RNA virus with no recognizable acute phase, quickly establishes persistence. We recently demonstrated that the vast majority of BDV genomes and antigenomes possess uniformly trimmed 5′ termini, even if the virus is recovered from complementary DNA encoding a hypothetical full-length viral genome. Here we discuss different mechanisms which might lead to the selective 5′-terminal trimming of the BDV genome and subsequent retrieval of the lost genetic information. We further discuss possible benefits of genome trimming in the light of recent findings that terminal RNA structures are recognized by intracellular sensors which trigger innate immunity. We hypothesize that 5′-terminal genome trimming might represent a smart strategy of BDV to evade the antiviral host response.