University of Toledo

Tomoaki Ogino

Non-segmented negative strand (NNS) RNA viruses belonging to the order Mononegavirales are highly diversified eukaryotic viruses including significant human pathogens, such as rabies, measles, Nipah, and Ebola. Most NNS RNA viruses replicate in the cytoplasm of host cells, whereas some NNS RNA viruses, such as bornaviruses, replicate in the nucleus. Mammalian Borna disease virus-1 (BoDV-1) is a causative agent of a fatal neurological disease in horses and sheep and has the potential to cause fatal encephalitis in humans. Our goal of this collaborative project is to define enzymatic roles of the multifunctional RNA-dependent RNA polymerase of BoDV-1 in viral genome replication and transcription. In contrast to other NNS RNA viruses, the 3′-termini of the BoDV-1 genome and anti-genome possess an extra 3′-ACAA sequence, which is required for efficient genome replication and transcription. However, how BoDV-1 generates and maintains the unique genome termini during replication remains elusive. Using a combination of biochemical and molecular virological approaches, we will elucidate the detailed mechanisms underlying the formation of the unique BoDV-1 genome termini during replication. This study will contribute to our understanding of biology of bornaviruses with zoonotic potential.